KDC-MN-265 – Kodiac biolabs

Our opinion on this compoundNiche research probe

43/100

Canonical PPAR-delta probe with real bench utility and a decisively dead translational path

Look, GW-501516 occupies a genuinely unusual position in the research compound landscape. It’s not a novel discovery and it’s not a failed hypothesis. It’s a tool with real utility that was abandoned for safety reasons, and understanding that distinction matters for how you think about it.

The mechanism is legitimate. PPAR-delta activation in skeletal muscle drives fatty acid oxidation and mitochondrial biogenesis through the PGC-1alpha axis. GSK’s phase 2 work in dyslipidemia showed real changes: HDL going up, triglycerides coming down. The biology is coherent and the compound does what it’s supposed to do. Thats actually part of what makes the carcinogenicity story so uncomfortable: this isn’t a failed mechanism, it’s a working mechanism in a compound that accelerates tumor growth at the same time.

The 2007 carcinogenicity data is what ended the GSK program. Long-term studies in both rats and mice showed dose-dependent tumor formation across multiple organ systems at every dose level tested. Not a marginal finding in one tissue at high dose: multiple tissues, multiple species, dose-response fully intact. WADA banned it in 2009. The recreational community largely ignored both of these facts, which is its own kind of signal about how people evaluate uncomfortable data when a compound does something they want it to do.

Here’s what keeps GW-501516 on the map for serious researchers: it remains the most well-characterized PPAR-delta agonist available for academic metabolic research. If you want to study PPAR-delta biology, fat oxidation pathways, mitochondrial biogenesis signaling, or the relationship between endurance capacity and substrate utilization, GW-501516 is still the reference compound. There arent many clean alternatives with comparable depth of characterization. That’s real bench value, and we give it credit for that specifically.

What it doesn’t have is a translational future. The clinical development program is dead and is not coming back. Any research program using this compound has to be oriented toward mechanistic probe work, not toward a clinical endpoint. That’s a legitimate scientific purpose, and there are genuine questions about PPAR-delta biology worth pursuing. But the constrained scope is real, and it shows up in the score.

We think the honest framing is: useful tool, dangerous compound, dead translational path. For a researcher working on PPAR-delta biology, muscle metabolism, or mitochondrial signaling in skeletal tissue, this compound is worth understanding. For anyone thinking about a translational arc or a human-facing program, there is nothing here to build toward. The score reflects that balance: a solid niche probe with no credible exit toward clinical relevance.

Novelty: 30
Mechanism promise: 38
In-category differentiation: 58
Evidence quality: 50
Translational signal: 30
Research bench value: 62

Rationale GW-501516 earns its differentiation and bench-value scores as the reference PPAR-delta agonist with genuine phase 2 lipid data, but tanks on translational signal and novelty because the clinical program is permanently closed by dose-dependent multi-organ carcinogenicity across both rodent species; no structural cap applies because the mechanism is intact and validated, only the safety profile is fatal.

PPAR-delta agonist (not a SARM)

A PPAR-delta agonist developed for dyslipidemia; widely used recreationally as an endurance enhancer despite cancer findings in long-term rodent studies.

Abstract

Cardarine (GW-501516, Endurobol; CAS 317318-70-0; molecular formula C21H18F3NO3S2; molecular weight 453.50) is a peroxisome proliferator-activated receptor delta (PPAR-delta) agonist developed at GlaxoSmithKline for dyslipidemia. The compound is not a SARM; it is grouped with SARMs in popular discourse owing to similar recreational use patterns. PPAR-delta activation in skeletal muscle increases fatty acid oxidation, mitochondrial biogenesis, and endurance capacity. Phase 2 trials in dyslipidemia demonstrated favorable lipid profile changes (HDL increase, triglyceride decrease). Development was halted by GSK in 2007 after long-term carcinogenicity studies in rats and mice showed dose-dependent tumor formation in multiple organs at all dose levels tested. The compound retains research utility as the canonical PPAR-delta agonist for academic metabolic research and is widely used recreationally despite the carcinogenicity signal; banned by WADA. Plasma half-life is approximately 24 hours.

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Tag: KDC-MN-265

Cardarine (GW-501516)

Abstract

Read the full monograph