I am not going to lie, I like being/getting lean.
So, any compounds that show promise in helping me achieve that goal. I am pretty interest in.
Several have caught my attention recently. but these are my top 3 right now.
SANA, SLU-PP-915, and ATX-304
None are peptides and none touch appetite. All of them work the expenditure side.
SLU-PP-915 (pan-ERR agonist)
Reptides link: https://reptides.co/p/slu-pp-915
Already wrote a full piece on this one so I'll keep it short-ish here.
ERRα, ERRβ and ERRγ are orphan nuclear receptors sitting in your muscle running the metabolic side of the house. Mitochondrial biogenesis, fatty acid oxidation, the Krebs cycle. 915 walks up and switches all three on.
Different molecule than 332, built to absorb orally since 332 doesn't. One less thing I'd need to pin, win.
Class: Synthetic small molecule pan-ERR (Estrogen Related Receptor) agonist Target: ERRα, ERRβ, ERRγ Route: Oral, the whole reason it exists Human data: Zero Status: Research chemical, RUO, grey market
What the mice got out of it
Billon, Appourchaux, Côté, Burris. J Pharmacol Exp Ther, Dec 2025. "An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity."
https://jpet.aspetjournals.org/article/S0022-3565(25)40300-0/fulltext
Ran farther and ran longer on the treadmill before hitting exhaustion. Muscle lit up the canonical ERR gene set, PGC-1α, PDK4, LDHA and Ddit4, the same program your muscle flips on after actual aerobic exercise. Oral held its own against i.p. once adjusted for systemic exposure.
915 matched 332 on distance and duration i.p., 20 mg/kg against 332's 50 mg/kg. The percentages come from the 332 study. 70% longer running time and 45% farther distance vs vehicle.
https://pubs.acs.org/doi/abs/10.1021/acschembio.2c00720
My n=1 update
Since the last write-up I've titrated 500 mcg up to 15 mg, and dropped the GW0742 because I wanna see what this SLU is all about.
Gas tank still feels bigger. Steady state and high volume rep work both feel like the ceiling moved, not like I'm stimmed.
15 mg is the first time I've been at or above the bottom rung of the mouse dose-response converted to HED, which was ~11 mg. Honestly I think 15 was a bit much. But idk, it's all just so subjective. I am still NOT 100% sold.
The mile test
Timed mile. Same route, same time of day, same shoes, same fed state. One week apart so the first mile doesn't train me into the second one. I never run so I am sure the first one will kill me regardless, so I need that time anyway lol.
One run on 915, one on nothing.
Problem is it has a very distinct taste. So, two identical caps, one with compound, one with filler. I will somehow need to convince my wife to do this for me. She picks which week gets which and doesn't tell me until both miles are on the clock.
Still n=1 but hey some data is more than no data, right?
ATX-304 / O304 (pan-AMPK activator)
Reptides link: https://reptides.co/p/atx-304
Out of Betagenon in Umeå, Sweden originally. Which kind of suprised me considering my perception was that everyone in Sweeden was skinny. Guess that is not the case... Cambrian Bio is running it now as an obesity and cardiometabolic drug.
AMPK gets switched on by a phosphate landing on Thr172, and PP2C spends all day pulling that phosphate back off. ATX-304 blocks the removal, so AMPK stays on regardless of your actual energy status.
Compare it to MOTS-C. MOTS-C fakes low energy. This one just disables the off switch.
It's also a mild uncoupler, so some of the energy your mitochondria would have put into ATP comes off as heat instead. DNP does the same thing with no ceiling, which is why it's extremely dangerous. This version is mild and secondary to the AMPK effect.
Class: Oral small molecule pan-AMPK activator, peripherally restricted. Not a peptide. Target: AMPK via PP2C inhibition, plus mild mitochondrial uncoupling Route: Oral Human data: Two trials. (YAY!) Status: Investigational, Phase 2 planned
The 2018 trial
Steneberg, Lindahl, Dahl et al. JCI Insight, Jun 2018. "PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients."
https://insight.jci.org/articles/view/99114
28-day phase IIa in T2D patients already on metformin. Fasting plasma glucose down, HOMA-IR improved, peripheral microvascular perfusion improved, blood pressure down, well tolerated.
The 2026 data
Cambrian presented first-in-human Phase 1b results at ADA in New Orleans in June, abstract #1782-P. 23 adults with obesity and prediabetes. Randomized, double-blind, placebo-controlled. 400 mg once daily for 8 weeks, then an 8-week open-label extension.
Resting metabolic rate up 8%, p<0.01 Plasma adiponectin up, p<0.01 Triglycerides down, p<0.01 Liver fat by MRI-PDFF down, p<0.05 Visceral adipose tissue down, p<0.05 Minimal weight loss at that exposure, which they said matched preclinical predictions TEAEs mild, similar frequency to placebo
Here's the part I did not expect. They monitored core body temperature continuously and 24-hour heart rate. Neither went up. No flushing. A companion poster, #1788-P, showed it activates AMPK without dropping cellular ATP.
An 8% bump in RMR with no measurable change in core temp is pretty cool ngl.
SANA / MVD1 (nitroalkene salicylate)
Reptides link: https://reptides.co/p/sana
Out of Eolo Pharma. First-in-class activator of creatine-dependent thermogenesis, which wasn't a drug class a few years ago. Cutting edge shit.
And this one has HUMAN data, which for something this new is not the norm. Randomized, double-blind, placebo-controlled, phase 1A and 1B, 41 participants, published alongside the mechanism paper.
https://pubmed.ncbi.nlm.nih.gov/40527924/
Brown fat makes heat through UCP1. There's a second route that doesn't need UCP1 at all. Futile creatine cycling.
SANA binds the mitochondrial creatine kinases CKMT1 and CKMT2 inside your fat cells and drives that cycle. Deplete creatine and the effect disappears completely.
No UCP1. No AMPK. No appetite effect.
Ngl, this shit confuses the hell out of me. So basically put, creatine normally works like a rechargeable battery. Phosphate goes on, phosphate comes off, and something on the other end uses that energy. That's why it helps you lift.
Futile cycling is that same loop with nothing plugged into it. Charge, discharge, charge, discharge, and you spend ATP every rotation for nothing. Energy leaves as heat. Revving an engine in neutral, and SANA puts a brick on the gas pedal.
Class: Investigational nitroalkene small molecule, 5-(2-nitroethenyl) salicylic acid Target: CKMT1 and CKMT2 Route: Oral Half-life: 1.6 to 2.0 hours in humans Human data: 41 participants, phase 1A/1B, ACTRN12622001519741 Status: Not approved anywhere
The mouse data
Less adiposity, higher energy expenditure, reduced liver steatosis and insulin resistance. 200 to 400 mg/kg/day oral, and 20 mg/kg/day subcutaneous.
The one that stops me. CKMT1 knockout mice on SANA at 20 mg/kg/day showed roughly a 50% increase in mortality after ONE week at room temperature. No deaths in wild type. Housing them at thermoneutrality rescued it completely.
Ngl when I read this shit, I kinda freaked out. They deleted CKMT1, one of the two enzymes SANA grabs onto. Take away a target and the drug should do less, not more. Instead it killed them.
Then the temperature part. Lab mice live at 72°F. To a mouse that's cold, and it burns a massive chunk of its daily energy just holding body temp there. Warm the room and nobody dies. Same drug, same dose.
Good news, I am not a mouse, although I tend to treat myself as such. 180 lbs in a shirt in a heated house. Whatever 72°F costs a mouse, it costs me basically nothing.
Bad news is those mice had zero copies of the gene. That basically doesn't happen in people. What people have is ordinary variation nobody has tested against this compound. Genotype dependent lethality with no way to check for it. I pulled my own Ancestry raw file and the gene isn't on there.
The human data
Phase 1A, single ascending dose. 200 / 400 / 800 mg once, healthy adults. Two of three participants at 800 mg developed reversible renal tubular injury.
Phase 1B, multiple ascending dose. 100 / 150 / 200 mg every 12 hours for 15 days. Up to 400 mg/day the profile was reported as overall favorable. Exploratory endpoint showed about 3% weight loss over 15 days in the six active participants at 400 mg/day, plus a HOMA-IR improvement.
Not powered for efficacy though.
Why this is the one I'd likely start with
New mechanism, not another version of something already in the stack. Oral. And it's been in people.
That last part is doing most of the work for me. Dose range, half-life, tolerability ceiling and a weight signal, all measured in humans instead of converted off a mouse with a body surface area formula.
The renal signal is at 800 mg single dose. The weight signal is at 400 mg/day split across two. I'd want to be nowhere near the top one.
Where I'm at
I still want a clearer read on 915, so I am going run a couple miles.
ATX-304 I'm warmer on than I was, purely because the fact it likely won't melt me from the inside like DNP would.
SANA is very interesting.
That's all, until next time.
-9th Life X: @James9thLife
(Not medical advice. All three are unapproved investigational compounds. SLU-PP-915 has zero published human trials, no established human dose and no safety profile. ATX-304 has human trial data but is not approved anywhere and is not available for human use outside a clinical trial. SANA/MVD1 is not approved, produced reversible renal tubular injury in two of three participants at 800 mg in phase 1, and carries a genotype-dependent mortality signal in CKMT1 knockout mice. Every animal dose above is what a study used, not a human protocol and not a human-equivalent conversion. For educational and research purposes only.)