YK-11: Steroidal SARM, Androgen Receptor Partial Agonism, Follistatin-Mediated Myostatin Inhibition, and Dual Anabolic-Osteogenic Activity in Research Models
YK11: Steroidal SARM, Androgen Receptor Partial Agonism, FollistatinMediated Myostatin Inhibition, and Dual AnabolicOsteogenic Activity in Research Models – research illustration Abstract & Overview YK11 — also designated Myostine and formally named (17α,20E)17,20[(1methoxyethylidene)bis(oxy)]3oxo19norpregna4,20diene21carboxylic acid methyl ester — is a synthetic steroidal selective androgen receptor modulator (SARM) first characterised by Kanno et al. at Toho University, Japan, in 2011 [1]. Unlike the majority of SARMs, which are nonsteroidal small molecules, YK11 is built upon a modified 19norpregnane steroid scaffold, placing it in a structurally distinct subclass of androgen receptor (AR) modulators. Its molecular formula is C₂₅H₃₄O₆ with a molar mass of 430.54 g/mol (CAS: 1370003761; PubChem CID: 119058028). YK11 operates through a dual pharmacological mechanism that distinguishes it from both classical anabolic steroids and conventional nonsteroidal SARMs. First, it functions as a geneselective partial agonist of the androgen receptor, binding the receptor’s ligandbinding domain without inducing the Nterminal/Cterminal (N/C) interaction required for full AR transactivation, thereby activating a distinct subset of androgenresponsive genes [1][2]. Second, and uniquely, YK11 induces the expression of follistatin (FST) in skeletal muscle cells — an effect not observed with dihydrotestosterone (DHT) — which in turn neutralises myostatin (GDF8), the primary endogenous inhibitor of skeletal muscle mass [2]. This dual mechanism positions YK11 as both a SARM and a functional myostatin inhibitor. “YK11 is a selective androgen receptor modulator (SARM), which activates AR without the N/C interaction… YK11 treatment of C2C12 cells, but not DHT, induced the expression of follistatin (Fst), and the YK11mediated myogenic differentiation was reversed by antiFst antibody. These results suggest that the induction of Fst is important for the anabolic effect of YK11.” — Kanno Y et al., Biol Pharm Bull (2013) [2]. Preclinical research has further demonstrated that YK11 promotes osteoblastic proliferation and differentiation via Akt signalling [3], attenuates sepsisinduced muscle wasting and reduces mortality in animal models through suppression of the TLR4/NFκB/TGFβ inflammatory cascade [4], and has been investigated for its effects on hippocampal function and oxidative stress [5][6]. YK11 has not received regulatory approval for human use and is classified as a designer drug and research compound. Molecular Identity and Structural Architecture YK11 is built upon a 19norpregnane steroidal backbone — the same core scaffold found in progestins such as norethisterone — with several key structural modifications that confer its unique pharmacological profile. The most distinctive feature is the 17α,20ketal group: a (1methoxyethylidene)bis(oxy) moiety bridging positions 17 and 20 of the steroid nucleus. This ketal group is the primary determinant of YK11’s selective AR binding profile, as it sterically prevents the receptor from adopting the conformation required for the N/C interaction. The molecule also bears a 3oxo4ene configuration (a conjugated enone in ring A, common to androgenic steroids) and a methyl ester at C21, which contributes to oral bioavailability and metabolic stability [1]. The steroidal nature of YK11 is pharmacologically significant. Most SARMs in research use — including RAD140, LGD4033, and Ostarine — are nonsteroidal compounds that bind the AR through entirely different chemical scaffolds. YK11’s steroid scaffold allows it to interact with the AR in a manner that more closely resembles natural androgens, yet the 17α,20ketal modification fundamentally alters the receptor’s conformational response, producing a geneselective activation pattern distinct from both testosterone and DHT. The compound is orally bioavailable with an estimated halflife of approximately 6 to 8 hours, necessitating multiple daily administrations in research protocols [1][2]. Mechanistic Rationale: Dual Pathway Anabolic Activity Androgen Receptor Partial Agonism and GeneSelective Activation Upon cellular uptake, YK11 binds to the ligandbinding domain (LBD/AF2) of the androgen receptor with high affinity. In contrast to full AR agonists such as DHT and testosterone, YK11 binding does not induce the physical interaction between the receptor’s Nterminal activation function 1 (NTD/AF1) and its ligandbinding domain activation function 2 (LBD/AF2) — a conformational event known as the N/C interaction that is required for maximal AR transactivation. The absence of this interaction means that YK11 activates only a subset of androgenresponsive genes, producing a tissueselective anabolic profile that theoretically spares androgenic side effects associated with full AR agonism [1]. Despite being a partial agonist, YK11 demonstrated greater anabolic potency than DHT in C2C12 murine myoblast cells in vitro, as measured by the induction of key myo
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