PNC-27

updated

PNC-27 is a laboratory peptide that joins a p53 fragment to a cell-penetrating domain. In cultured cancer cells, in cells taken from two patients with ovarian cancer and treated outside the body, and in mouse leukemia models, it killed cancer cells by membrane lysis. No controlled human study exists, and no human has been given it: ClinicalTrials.gov queries and a Drugs@FDA query on 9 October 2026 found no study and no matching application. This page presents it as a laboratory compound only.

Chimeric p53-derived peptide (HDM-2-binding domain joined to a penetratin domain)

  • PubChem lists PNC-27 as CID 16201774, C188H293N53O44S, molecular weight 4032, CAS 1159861-00-3: an HDM-2-binding domain matching residues 12 to 26 of p53, attached to a penetratin transmembrane domain.
  • HDM-2 was found in the membranes of a variety of cancer cells but not in several untransformed cell lines, and adding membrane-localized HDM-2 to untransformed MCF-10-2A cells made them susceptible to PNC-27.
  • In primary cultures from two patients with ovarian cancer, PNC-27 inhibited growth and was cytotoxic in a dose-dependent way while the control peptide PNC-29 had no effect; no patient received the peptide.
  • In human and murine leukemia models, PNC-27 killed leukemia blasts and stem cells in primary and secondary transplant experiments while sparing normal hematopoietic stem cell activity in wild-type mice; Oncolyze, Inc supplied the peptide for that study.
  • ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies on 9 October 2026, and a Drugs@FDA query through openFDA for PNC-27 returned no matching application.
  • Every efficacy result is in cultured cells, in patient-derived cells treated outside the body, or in mice.

What is PNC-27, and is it approved for anything?

PNC-27 is a laboratory peptide made of a p53 fragment joined to a penetratin cell-penetrating domain. There is no approved or validated human use: no registered clinical trial and no FDA application appear in the records reviewed, and no human has been given it.

PubChem lists PNC-27 as CID 16201774, C188H293N53O44S, molecular weight 4032, CAS 1159861-00-3. It is a chimeric peptide: an HDM-2-binding domain corresponding to residues 12 to 26 of p53, attached to a transmembrane-penetrating (penetratin) domain. The related peptides in the same series, PNC-28 and the inactive control PNC-29, are different molecules, and their results are not pooled with PNC-27's here.

There is no approved or validated human use. On 9 October 2026, ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies, and a Drugs@FDA query through the openFDA API on the name PNC-27 returned no matching application. The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data.

The openFDA query returns approved applications only, so its empty result shows that there is no approval, not that no investigational application exists. Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established here.

Every efficacy result on this page is in cultured cells, in cells taken from patients and treated outside the body, or in mice. This page presents PNC-27 as a laboratory compound and nothing else.

PubChem: PNC-27 identity, chimeric p53-penetratin peptide

Chemical identity record

National Library of Medicine. PubChem compound record CID 16201774 (PNC-27).

PubChem lists PNC-27 as CID 16201774, C188H293N53O44S, molecular weight 4032, CAS 1159861-00-3. It is a chimeric peptide: an HDM-2-binding domain corresponding to residues 12 to 26 of p53, attached to a transmembrane-penetrating (penetratin) domain.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic chimeric peptide
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The related peptides in the same series, PNC-28 and the inactive control PNC-29, are different molecules, and their results should not be pooled with PNC-27's.

Read the original source
Registry and FDA application searches, 9 October 2026: no study, no application

Trial registry record

ClinicalTrials.gov queries for PNC-27 and for PNC-27 peptide cancer, and a Drugs@FDA query through the openFDA API on the brand and generic name PNC-27, all run on 9 October 2026.

ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies, so there are no registered studies and no posted results. A Drugs@FDA query through the openFDA API on the name PNC-27 returned no matching application. The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data for PNC-27. Every efficacy result on this page is in cultured cells, in cells taken from patients and treated outside the body, or in mice.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Queries run on 9 October 2026
Study design
Registry and regulatory database queries
Funding
not stated in the source

The openFDA Drugs@FDA query returns approved applications only, so its empty result establishes only that there is no approval, not that no investigational application exists. Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established here.

Read the original source

What have cell and mouse studies found?

In cultured cells PNC-27 killed cancer cells but not untransformed cells by membrane lysis, and adding membrane HDM-2 made resistant untransformed cells susceptible. In mouse leukemia models it killed leukemia blasts and stem cells while sparing normal blood stem cells.

In cultured cells, PNC-27 killed cancer cells but not normal cells by inducing membranolysis. The p53 residues of PNC-27 have a 3D structure directly superimposable on the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible. That transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed.

In a labeled-peptide experiment, PNC-27 labeled green at the amino terminus and red at the carboxyl terminus produced punctate combined yellow fluorescence in the membrane of MCF-7 breast cancer cells at 30 minutes, indicating intact peptide, increasing during cell lysis. Untransformed MCF-10-2A cells showed an initial uniform yellow membrane fluorescence that subsequently disappeared, and those cells remained viable. The authors concluded that the intact whole peptide, not fragments, induces the membrane lysis.

The strongest in vivo result comes from an independent group at an academic cancer center. Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

The authors of the leukemia study disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study. This is a mouse result, and the information reviewed does not state a route or amount for the in vivo experiments, so none is given here.

Cell lines: membrane HDM-2 in cancer cells, killing without it absent, transfection adds susceptibility

Cell study

Sarafraz-Yazdi E et al. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID 20080680.

PNC-27 kills cancer cells but not normal cells by inducing membranolysis. The previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure of the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible.

Participants / model
Human cancer cell lines and untransformed cell lines
Treatment
Peptide applied to cultured cells; plasmid transfection
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed. These are cultured cells.

Read the original source
Labeled peptide: intact whole peptide lyses MCF-7 cells, untransformed cells stay viable

Cell study

Sookraj KA et al. Cancer Chemother Pharmacol. 2010;66(2):325-31. PMID 20182728.

Using PNC-27 labeled green at the amino terminus and red at the carboxyl terminus, MCF-7 breast cancer cells showed significant punctate combined yellow fluorescence in the membrane at 30 minutes, indicating intact peptide, increasing during cell lysis. Untransformed MCF-10-2A cells showed an initial uniform combined yellow membrane fluorescence that subsequently disappeared, and those cells remained viable. The authors concluded the intact whole peptide, not fragments, induces the membrane lysis.

Participants / model
MCF-7 breast cancer cells; untransformed MCF-10-2A breast epithelial cells
Treatment
Double-labeled peptide applied to cultured cells
Follow-up
Fluorescence followed from 30 minutes
Study design
Original preclinical study
Funding
not stated in the source

Cultured cells only.

Read the original source
Leukemia models: independent group, primary and secondary transplants, normal stem cells spared in mice

Animal study

Wang H et al. Leukemia. 2020;34(1):75-86. PMID 31337857.

Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

Participants / model
Human and mouse acute myeloid leukemia blasts; transplanted mice; wild-type mice for the normal stem cell arm
Treatment
PNC-27 in vivo as dosed in the report; route and amount not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study with primary and secondary transplant experiments and a normal stem cell control arm
Funding
The authors disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study.

This is the strongest in vivo result and comes from an independent group, an academic cancer center. The supply of PNC-27 by a commercial sponsor should be read with it. It is a mouse result.

Read the original source

What happened in cells taken from patients?

In primary cultures from two patients with ovarian cancer, PNC-27 inhibited growth and was cytotoxic in a dose-dependent way, while the control peptide PNC-29 had no effect. The cells were treated in culture, and no patient received the peptide.

Primary cultures were established from freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas, yielding two cell lines, one from a mucinous cystadenocarcinoma and one from a high-grade papillary serous carcinoma. PNC-27 inhibited growth in a dose-dependent manner and was cytotoxic to both, measured by MTT and lactate dehydrogenase release, while the control peptide PNC-29 had no effect.

It was also cytotoxic to long-established and chemotherapy-resistant human ovarian cancer cell lines in culture.

No patient received the peptide. The cells were exposed to it in culture, outside the body.

Patient-derived ovarian cells treated outside the body: growth inhibited, control peptide inactive

Cell study

Sarafraz-Yazdi E et al. Ann Clin Lab Sci. 2015;45(6):650-8. PMID 26663795.

Primary cultures were established from freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas, yielding two cell lines, one from a mucinous cystadenocarcinoma and one from a high-grade papillary serous carcinoma. PNC-27 inhibited growth in a dose-dependent manner and was cytotoxic to both, measured by MTT and lactate dehydrogenase release, while the control peptide PNC-29 had no effect. It was also cytotoxic to long-established and chemotherapy-resistant human ovarian cancer cell lines.

Participants / model
Primary cultures from two patients with epithelial ovarian cancer; established ovarian cancer cell lines
Treatment
Peptide applied to cultured cells ex vivo
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

No patient received the peptide. The cells were exposed to it in culture.

Read the original source

Does any record support the oncology use sellers describe?

No. The HDM2 targeting and selective killing seen in the laboratory is supported in cultured cells, in patient-derived cells treated outside the body and in mouse leukemia models, but the oncology use claim is not supported, because no human has been given PNC-27 in any record reviewed.

Sellers describe PNC-27 for experimental oncology use as a targeted apoptosis inducer for HDM2-overexpressing cancers.

The mechanism is supported in the laboratory: HDM2 targeting and selective killing in cultured cells, in cells taken from patients and treated outside the body, and in mouse leukemia models. The oncology use claim is not supported, because no human has been given PNC-27 in any record reviewed.

ClinicalTrials.gov queries on 9 October 2026 for PNC-27 and PNC-27 peptide cancer returned no studies, and a Drugs@FDA query returned no matching application. There is no basis in these records for discussing use in a person, and PNC-27 is not described on this page as a therapy, an alternative or an option for anyone.

Cell lines: membrane HDM-2 in cancer cells, killing without it absent, transfection adds susceptibility

Cell study

Sarafraz-Yazdi E et al. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID 20080680.

PNC-27 kills cancer cells but not normal cells by inducing membranolysis. The previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure of the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible.

Participants / model
Human cancer cell lines and untransformed cell lines
Treatment
Peptide applied to cultured cells; plasmid transfection
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed. These are cultured cells.

Read the original source
Patient-derived ovarian cells treated outside the body: growth inhibited, control peptide inactive

Cell study

Sarafraz-Yazdi E et al. Ann Clin Lab Sci. 2015;45(6):650-8. PMID 26663795.

Primary cultures were established from freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas, yielding two cell lines, one from a mucinous cystadenocarcinoma and one from a high-grade papillary serous carcinoma. PNC-27 inhibited growth in a dose-dependent manner and was cytotoxic to both, measured by MTT and lactate dehydrogenase release, while the control peptide PNC-29 had no effect. It was also cytotoxic to long-established and chemotherapy-resistant human ovarian cancer cell lines.

Participants / model
Primary cultures from two patients with epithelial ovarian cancer; established ovarian cancer cell lines
Treatment
Peptide applied to cultured cells ex vivo
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

No patient received the peptide. The cells were exposed to it in culture.

Read the original source
Leukemia models: independent group, primary and secondary transplants, normal stem cells spared in mice

Animal study

Wang H et al. Leukemia. 2020;34(1):75-86. PMID 31337857.

Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

Participants / model
Human and mouse acute myeloid leukemia blasts; transplanted mice; wild-type mice for the normal stem cell arm
Treatment
PNC-27 in vivo as dosed in the report; route and amount not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study with primary and secondary transplant experiments and a normal stem cell control arm
Funding
The authors disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study.

This is the strongest in vivo result and comes from an independent group, an academic cancer center. The supply of PNC-27 by a commercial sponsor should be read with it. It is a mouse result.

Read the original source
Registry and FDA application searches, 9 October 2026: no study, no application

Trial registry record

ClinicalTrials.gov queries for PNC-27 and for PNC-27 peptide cancer, and a Drugs@FDA query through the openFDA API on the brand and generic name PNC-27, all run on 9 October 2026.

ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies, so there are no registered studies and no posted results. A Drugs@FDA query through the openFDA API on the name PNC-27 returned no matching application. The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data for PNC-27. Every efficacy result on this page is in cultured cells, in cells taken from patients and treated outside the body, or in mice.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Queries run on 9 October 2026
Study design
Registry and regulatory database queries
Funding
not stated in the source

The openFDA Drugs@FDA query returns approved applications only, so its empty result establishes only that there is no approval, not that no investigational application exists. Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established here.

Read the original source

How does PNC-27 kill cells in the laboratory?

PNC-27 binds HDM-2 found in the membranes of the cancer cells studied and lyses the membrane. Untransformed cells that lack membrane HDM-2 were spared until the target was added by transfection. No half-life or exposure data exist for any species.

PNC-27 pairs an HDM-2-binding domain, residues 12 to 26 of p53, with a penetratin transmembrane domain. In cell studies it binds HDM-2 found in the membranes of a variety of cancer cells but not in several untransformed cell lines, and kills cancer cells by inducing membranolysis.

Adding full-length HDM-2 with a membrane-localization signal to untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made them susceptible. The labeled-peptide experiment indicated that the intact whole peptide, not fragments, induces the membrane lysis.

In leukemia models, PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis.

The records reviewed contain no pharmacokinetic data in any species, so no half-life is given.

PubChem: PNC-27 identity, chimeric p53-penetratin peptide

Chemical identity record

National Library of Medicine. PubChem compound record CID 16201774 (PNC-27).

PubChem lists PNC-27 as CID 16201774, C188H293N53O44S, molecular weight 4032, CAS 1159861-00-3. It is a chimeric peptide: an HDM-2-binding domain corresponding to residues 12 to 26 of p53, attached to a transmembrane-penetrating (penetratin) domain.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic chimeric peptide
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The related peptides in the same series, PNC-28 and the inactive control PNC-29, are different molecules, and their results should not be pooled with PNC-27's.

Read the original source
Cell lines: membrane HDM-2 in cancer cells, killing without it absent, transfection adds susceptibility

Cell study

Sarafraz-Yazdi E et al. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID 20080680.

PNC-27 kills cancer cells but not normal cells by inducing membranolysis. The previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure of the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible.

Participants / model
Human cancer cell lines and untransformed cell lines
Treatment
Peptide applied to cultured cells; plasmid transfection
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed. These are cultured cells.

Read the original source
Labeled peptide: intact whole peptide lyses MCF-7 cells, untransformed cells stay viable

Cell study

Sookraj KA et al. Cancer Chemother Pharmacol. 2010;66(2):325-31. PMID 20182728.

Using PNC-27 labeled green at the amino terminus and red at the carboxyl terminus, MCF-7 breast cancer cells showed significant punctate combined yellow fluorescence in the membrane at 30 minutes, indicating intact peptide, increasing during cell lysis. Untransformed MCF-10-2A cells showed an initial uniform combined yellow membrane fluorescence that subsequently disappeared, and those cells remained viable. The authors concluded the intact whole peptide, not fragments, induces the membrane lysis.

Participants / model
MCF-7 breast cancer cells; untransformed MCF-10-2A breast epithelial cells
Treatment
Double-labeled peptide applied to cultured cells
Follow-up
Fluorescence followed from 30 minutes
Study design
Original preclinical study
Funding
not stated in the source

Cultured cells only.

Read the original source
Leukemia models: independent group, primary and secondary transplants, normal stem cells spared in mice

Animal study

Wang H et al. Leukemia. 2020;34(1):75-86. PMID 31337857.

Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

Participants / model
Human and mouse acute myeloid leukemia blasts; transplanted mice; wild-type mice for the normal stem cell arm
Treatment
PNC-27 in vivo as dosed in the report; route and amount not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study with primary and secondary transplant experiments and a normal stem cell control arm
Funding
The authors disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study.

This is the strongest in vivo result and comes from an independent group, an academic cancer center. The supply of PNC-27 by a commercial sponsor should be read with it. It is a mouse result.

Read the original source

What risks and unknowns do the records show?

No human has been given PNC-27, so no human dose, pharmacokinetic or safety data exist. It acts by lysing membranes, and selectivity for cancer cells over normal cells is shown only in cultured cells, patient-derived cells treated outside the body and mouse models.

The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data for PNC-27.

PNC-27 kills cells by membrane lysis. In the laboratory, untransformed cells that lack membrane HDM-2 were spared, and in the mouse leukemia models normal hematopoietic stem cell activity was spared in wild-type mice. That selectivity is shown only in cultured cells, patient-derived cells treated outside the body and mice, and nothing is known about effects in a person.

Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established, because the openFDA query returns approved applications only. The related peptides PNC-28 and PNC-29 are different molecules, and their results are not pooled with PNC-27's.

Registry and FDA application searches, 9 October 2026: no study, no application

Trial registry record

ClinicalTrials.gov queries for PNC-27 and for PNC-27 peptide cancer, and a Drugs@FDA query through the openFDA API on the brand and generic name PNC-27, all run on 9 October 2026.

ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies, so there are no registered studies and no posted results. A Drugs@FDA query through the openFDA API on the name PNC-27 returned no matching application. The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data for PNC-27. Every efficacy result on this page is in cultured cells, in cells taken from patients and treated outside the body, or in mice.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Queries run on 9 October 2026
Study design
Registry and regulatory database queries
Funding
not stated in the source

The openFDA Drugs@FDA query returns approved applications only, so its empty result establishes only that there is no approval, not that no investigational application exists. Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established here.

Read the original source
Cell lines: membrane HDM-2 in cancer cells, killing without it absent, transfection adds susceptibility

Cell study

Sarafraz-Yazdi E et al. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID 20080680.

PNC-27 kills cancer cells but not normal cells by inducing membranolysis. The previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure of the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible.

Participants / model
Human cancer cell lines and untransformed cell lines
Treatment
Peptide applied to cultured cells; plasmid transfection
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed. These are cultured cells.

Read the original source
Leukemia models: independent group, primary and secondary transplants, normal stem cells spared in mice

Animal study

Wang H et al. Leukemia. 2020;34(1):75-86. PMID 31337857.

Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

Participants / model
Human and mouse acute myeloid leukemia blasts; transplanted mice; wild-type mice for the normal stem cell arm
Treatment
PNC-27 in vivo as dosed in the report; route and amount not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study with primary and secondary transplant experiments and a normal stem cell control arm
Funding
The authors disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study.

This is the strongest in vivo result and comes from an independent group, an academic cancer center. The supply of PNC-27 by a commercial sponsor should be read with it. It is a mouse result.

Read the original source

Why does PNC-27 sit in C tier?

The laboratory case has held up for more than 20 years across at least two independent groups, with a specific mechanism, but no human has been given PNC-27 and there is no registered trial or FDA application. It is a laboratory compound.

The laboratory case has held up for more than 20 years and across at least two independent groups, including a leukemia paper from an academic cancer center with in vivo primary and secondary transplant experiments in human and murine models and a normal hematopoietic stem cell control arm. The mechanism is specific and testable, and the transfection experiment, where adding membrane HDM-2 to resistant untransformed cells made them susceptible, is a strong piece of laboratory evidence.

None of that has produced a clinical trial. There is no registered study, no FDA application in the records reviewed, no human dose and no human safety data, so there is no basis for discussing use. A molecule that lyses membranes and has never been given to a person is a laboratory compound and nothing else.

Cell lines: membrane HDM-2 in cancer cells, killing without it absent, transfection adds susceptibility

Cell study

Sarafraz-Yazdi E et al. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID 20080680.

PNC-27 kills cancer cells but not normal cells by inducing membranolysis. The previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure of the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible.

Participants / model
Human cancer cell lines and untransformed cell lines
Treatment
Peptide applied to cultured cells; plasmid transfection
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed. These are cultured cells.

Read the original source
Leukemia models: independent group, primary and secondary transplants, normal stem cells spared in mice

Animal study

Wang H et al. Leukemia. 2020;34(1):75-86. PMID 31337857.

Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

Participants / model
Human and mouse acute myeloid leukemia blasts; transplanted mice; wild-type mice for the normal stem cell arm
Treatment
PNC-27 in vivo as dosed in the report; route and amount not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study with primary and secondary transplant experiments and a normal stem cell control arm
Funding
The authors disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study.

This is the strongest in vivo result and comes from an independent group, an academic cancer center. The supply of PNC-27 by a commercial sponsor should be read with it. It is a mouse result.

Read the original source
Registry and FDA application searches, 9 October 2026: no study, no application

Trial registry record

ClinicalTrials.gov queries for PNC-27 and for PNC-27 peptide cancer, and a Drugs@FDA query through the openFDA API on the brand and generic name PNC-27, all run on 9 October 2026.

ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies, so there are no registered studies and no posted results. A Drugs@FDA query through the openFDA API on the name PNC-27 returned no matching application. The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data for PNC-27. Every efficacy result on this page is in cultured cells, in cells taken from patients and treated outside the body, or in mice.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Queries run on 9 October 2026
Study design
Registry and regulatory database queries
Funding
not stated in the source

The openFDA Drugs@FDA query returns approved applications only, so its empty result establishes only that there is no approval, not that no investigational application exists. Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established here.

Read the original source

Studies and sources

Registry and FDA application searches, 9 October 2026: no study, no application

Trial registry record

ClinicalTrials.gov queries for PNC-27 and for PNC-27 peptide cancer, and a Drugs@FDA query through the openFDA API on the brand and generic name PNC-27, all run on 9 October 2026.

ClinicalTrials.gov queries for PNC-27 and PNC-27 peptide cancer returned no studies, so there are no registered studies and no posted results. A Drugs@FDA query through the openFDA API on the name PNC-27 returned no matching application. The records reviewed contain no registered clinical trial, no FDA application, no human dose, no human pharmacokinetics and no human safety data for PNC-27. Every efficacy result on this page is in cultured cells, in cells taken from patients and treated outside the body, or in mice.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Queries run on 9 October 2026
Study design
Registry and regulatory database queries
Funding
not stated in the source

The openFDA Drugs@FDA query returns approved applications only, so its empty result establishes only that there is no approval, not that no investigational application exists. Whether PNC-27 holds an FDA orphan drug designation or an active investigational new drug application is not established here.

Read the original source
PubChem: PNC-27 identity, chimeric p53-penetratin peptide

Chemical identity record

National Library of Medicine. PubChem compound record CID 16201774 (PNC-27).

PubChem lists PNC-27 as CID 16201774, C188H293N53O44S, molecular weight 4032, CAS 1159861-00-3. It is a chimeric peptide: an HDM-2-binding domain corresponding to residues 12 to 26 of p53, attached to a transmembrane-penetrating (penetratin) domain.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined synthetic chimeric peptide
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

The related peptides in the same series, PNC-28 and the inactive control PNC-29, are different molecules, and their results should not be pooled with PNC-27's.

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Cell lines: membrane HDM-2 in cancer cells, killing without it absent, transfection adds susceptibility

Cell study

Sarafraz-Yazdi E et al. Proc Natl Acad Sci U S A. 2010;107(5):1918-23. PMID 20080680.

PNC-27 kills cancer cells but not normal cells by inducing membranolysis. The previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure of the same residues bound to HDM-2. Significant levels of HDM-2 were found in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, and in colocalization experiments PNC-27 bound cell membrane-bound HDM-2. Transfecting a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells, which are not susceptible to PNC-27, made those cells susceptible.

Participants / model
Human cancer cell lines and untransformed cell lines
Treatment
Peptide applied to cultured cells; plasmid transfection
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The transfection experiment is the strongest part of the selectivity case: the target was added, and the killing followed. These are cultured cells.

Read the original source
Labeled peptide: intact whole peptide lyses MCF-7 cells, untransformed cells stay viable

Cell study

Sookraj KA et al. Cancer Chemother Pharmacol. 2010;66(2):325-31. PMID 20182728.

Using PNC-27 labeled green at the amino terminus and red at the carboxyl terminus, MCF-7 breast cancer cells showed significant punctate combined yellow fluorescence in the membrane at 30 minutes, indicating intact peptide, increasing during cell lysis. Untransformed MCF-10-2A cells showed an initial uniform combined yellow membrane fluorescence that subsequently disappeared, and those cells remained viable. The authors concluded the intact whole peptide, not fragments, induces the membrane lysis.

Participants / model
MCF-7 breast cancer cells; untransformed MCF-10-2A breast epithelial cells
Treatment
Double-labeled peptide applied to cultured cells
Follow-up
Fluorescence followed from 30 minutes
Study design
Original preclinical study
Funding
not stated in the source

Cultured cells only.

Read the original source
Patient-derived ovarian cells treated outside the body: growth inhibited, control peptide inactive

Cell study

Sarafraz-Yazdi E et al. Ann Clin Lab Sci. 2015;45(6):650-8. PMID 26663795.

Primary cultures were established from freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas, yielding two cell lines, one from a mucinous cystadenocarcinoma and one from a high-grade papillary serous carcinoma. PNC-27 inhibited growth in a dose-dependent manner and was cytotoxic to both, measured by MTT and lactate dehydrogenase release, while the control peptide PNC-29 had no effect. It was also cytotoxic to long-established and chemotherapy-resistant human ovarian cancer cell lines.

Participants / model
Primary cultures from two patients with epithelial ovarian cancer; established ovarian cancer cell lines
Treatment
Peptide applied to cultured cells ex vivo
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

No patient received the peptide. The cells were exposed to it in culture.

Read the original source
Leukemia models: independent group, primary and secondary transplants, normal stem cells spared in mice

Animal study

Wang H et al. Leukemia. 2020;34(1):75-86. PMID 31337857.

Membrane HDM2 was found exclusively on human and mouse acute myeloid leukemia blasts, including leukemia stem cell enriched subpopulations, but not on normal hematopoietic stem cells, and higher membrane HDM2 levels were associated with leukemia-initiating capacity, quiescence and chemoresistance. PNC-27 bound membrane HDM2 and enhanced its interaction with E-cadherin, leading to E-cadherin ubiquitination and degradation, membrane damage and cell death by necrobiosis. In vivo, PNC-27 significantly killed both bulk leukemia blasts and leukemia stem cells in primary and secondary transplant experiments using human and murine models, while sparing normal hematopoietic stem cell activity in primary and secondary bone marrow transplants of wild-type mice.

Participants / model
Human and mouse acute myeloid leukemia blasts; transplanted mice; wild-type mice for the normal stem cell arm
Treatment
PNC-27 in vivo as dosed in the report; route and amount not stated in the information reviewed
Follow-up
not stated in the source
Study design
Original preclinical study with primary and secondary transplant experiments and a normal stem cell control arm
Funding
The authors disclose that Oncolyze, Inc provided PNC-27, PNC-26 and PNC-29 for the study.

This is the strongest in vivo result and comes from an independent group, an academic cancer center. The supply of PNC-27 by a commercial sponsor should be read with it. It is a mouse result.

Read the original source

Why is PNC-27 in C tier?

C fits a laboratory case that has held up for more than 20 years across at least two independent groups, with a specific and testable mechanism and no human exposure. There is no registered study, no FDA application in the records reviewed, no human dose and no human safety data, so there is no basis for discussing use. PNC-27 is a laboratory compound and nothing else.