TFM-4AS-1

Overview

TFM-4AS-1 (PubChem CID 10277123; also indexed as HY-103246 / CS-0026116) is a preclinical, STEROIDAL selective androgen receptor modulator (SARM) — specifically a 4-azasteroid. It is NOT a peptide (it is not an amino-acid chain) and, importantly, it is NOT one of the more familiar nonsteroidal arylpropionamide SARMs such as ostarine or testolone (RAD-140). It appears in this peptide reference because it is discussed alongside SARMs and peptides in the "research chemical" community — not because it is one.

TFM-4AS-1 was described by Merck Research Laboratories medicinal chemists in a single characterization paper (Schmidt et al., J Biol Chem 2009; PMID 19846549). What makes it unusual is a dual mechanism: it is a partial agonist of the androgen receptor (AR) that simultaneously inhibits both isoforms of 5α-reductase (the enzyme that converts testosterone to the more potent DHT). In the AR N-terminal/C-terminal (N/C) interaction assay it behaves as an antagonist, and this is proposed to underlie its gene- and tissue-selective profile. Its highest phase of development is preclinical — it is a research-reagent / probe compound used to study AR N/C interactions, with no human trials. A structurally related successor compound, MK-0773, was advanced further in Merck's 4-azasteroid SARM program; TFM-4AS-1 itself was not the clinical candidate.

Chemistry and structure

TFM-4AS-1 is a steroidal small molecule — a 4-azasteroid — an amino-acid chain it is not.

Mechanism of action

• Androgen receptor (AR) — partial agonist. TFM-4AS-1 binds the AR with IC50 ~30-38 nM and drives AR-dependent transcription to only ~55% of the maximal response (Emax ~55%) — i.e. a partial agonist, not a full agonist. [In vitro] (Schmidt et al., 2009; PMID 19846549)
• AR N-terminal/C-terminal (N/C) interaction — antagonist. In the assay measuring the intramolecular N/C interaction required for full receptor activation, TFM-4AS-1 acts as an antagonist of that interaction. This is the proposed molecular basis for its gene-selective / tissue-selective effects. [In vitro] (PMID 19846549)
• 5α-reductase type I — inhibitor. Inhibits 5α-reductase type I with IC50 ~2 nM, blocking conversion of testosterone to dihydrotestosterone (DHT). [In vitro] (PMID 19846549)
• 5α-reductase type II — inhibitor. Inhibits 5α-reductase type II with IC50 ~3 nM. Combined type I/II inhibition lowers local DHT, contributing to reduced androgenic activity in DHT-dependent tissues (prostate, seminal vesicle, sebaceous gland). [In vitro] (PMID 19846549)
• Tissue-selective androgen action in vivo. In ovariectomized rats, TFM-4AS-1 promoted bone and muscle accrual comparable to DHT while only weakly stimulating prostate growth, stimulating sebaceous gland formation only ~31% as much as DHT, and partially antagonizing DHT-induced seminal-vesicle growth. This dissociation of anabolic from androgenic/reproductive/sebaceous action is the defining SARM property being probed. [Animal] (PMID 19846549)

Research and evidence

The evidence base is entirely preclinical (in vitro + ovariectomized rats), from a single research group (Merck). There are no human trials of TFM-4AS-1 for any indication.

Human evidence in context. There is none. TFM-4AS-1 has no human clinical trial, so there are no completed human studies establishing efficacy for bone, muscle, or any medical indication. All effect claims rest on rat studies and in-vitro assays from one paper by one group. Human pharmacokinetics — half-life, oral bioavailability, ADME, and metabolite profile — are not established / not found in sources. Whether TFM-4AS-1 itself ever entered formal IND-enabling development is not established — its successor MK-0773 was advanced instead.

Status and regulation

• Regulatory approval: None. TFM-4AS-1 is not approved by the FDA, the EMA, or any other regulator for any indication. Its highest phase is preclinical (in vitro + rats) — there are no human trials. It functions as a research reagent / probe compound.
• Anti-doping: As a SARM, TFM-4AS-1 falls under the World Anti-Doping Agency (WADA) Prohibited List class S1.2 (Other Anabolic Agents — SARMs), prohibited at all times (in- and out-of-competition) for all athletes. WADA sport-eligibility is a separate axis from legality.
• Market reality: Outside the laboratory it would be sold only as an unregulated "research chemical" of unknown identity, purity, and potency (see Safety).

Safety

Documented and expected safety signals (tagged by evidence type):

• No human safety data [Human]. TFM-4AS-1 has no human pharmacokinetic, efficacy, or safety data. Absence of trials means human adverse effects are unquantified, not absent.
• SARM-class hepatotoxicity / drug-induced liver injury (DILI) [Human]. The FDA has warned that SARMs as a class are associated with serious or life-threatening liver injury, including acute liver failure. Class-level, not established specifically for TFM-4AS-1, which has no human exposure. Source: FDA SARM consumer update.
• Testosterone / HPTA suppression [Hypothesis]. AR-active SARMs characteristically suppress endogenous testosterone and the HPTA. Not measured for TFM-4AS-1; inferred class risk only.
• Partial androgen / anti-androgen activity in reproductive tissue [Animal]. In rats TFM-4AS-1 antagonized DHT in seminal vesicles and only weakly stimulated the prostate — the intended selectivity — but the human consequences (including potential anti-androgenic effects) are unknown. Source: PMID 19846549.

Legal status

How it compares

TFM-4AS-1 is often grouped with other SARMs and "research chemicals." The honest framing:

• Ostarine and testolone (RAD-140) — nonsteroidal arylpropionamide/oxadiazole SARMs. TFM-4AS-1 is a different chemical class: a steroidal 4-azasteroid with a dual AR-partial-agonist + 5α-reductase-inhibitor mechanism. Those compounds have human clinical data that TFM-4AS-1 entirely lacks.
• Other steroidal / dual Merck SARM work — TFM-4AS-1's successor MK-0773 was the compound advanced further in the 4-azasteroid program; TFM-4AS-1 remained a probe compound.

The decisive point: TFM-4AS-1 is a preclinical, unapproved research reagent with a tissue-selective anabolic profile shown only in rats and in vitro, from a single paper. It is not a "milder, safer, or legal alternative to steroids," and its rat/in-vitro selectivity is not a human safety claim. See the Muscle, growth & hormones overview.

Common misconceptions

• "TFM-4AS-1 is a peptide." No. It is a steroidal small molecule — a 4-azasteroid (C27H33F3N2O2, 474.6 g/mol). It is covered here only because it is discussed and stacked with SARMs and peptides.
• "It's just another SARM like ostarine or RAD-140." No. Those are nonsteroidal arylpropionamide-type SARMs. TFM-4AS-1 is steroidal (a 4-azasteroid) with a dual mechanism — a partial AR agonist that also inhibits 5α-reductase.
• "It's a proven anabolic with human evidence." No. All effect data are from rat models and in-vitro assays in one 2009 Merck paper; there are no human trials and no human efficacy, safety, or dosing data.
• "It's a milder, safer, legal alternative to steroids." No. It is not approved, has no human safety data, and its drug class is FDA-flagged for liver injury and testosterone suppression. "SARM" does not mean "safe."
• "If it's labeled TFM-4AS-1, that's what's in it." Not reliably. In the JAMA 2017 analysis, only about half of products sold as SARMs contained the labeled compound; many contained a different drug or nothing active.

---

This entry is educational and summarizes published research and public regulatory information as of the "updated" date above. It is not medical advice, not legal advice, a recommendation, or a guide to obtaining or using any substance. Last reviewed 2026-07-10.