RU-58841 (5%)

RU-58841 (5%)

RU-58841 is a non-steroidal topical androgen receptor antagonist that competitively inhibits DHT binding in hair follicle androgen receptors with high affinity (Kd 1.8 nM) and minimal systemic absorption.

In stock

Description

Summary Abstract

RU-58841 (PSK-3841; CAS 154992-24-2) is a synthetic non-steroidal antiandrogen designed for topical application. It functions as a competitive antagonist at the androgen receptor (AR), binding the receptor’s ligand-binding domain (LBD) with high affinity across species — Kd values of 1.8 nM (human), 1.1 nM (rat), and 1.3–1.4 nM (hamster) — and preventing endogenous androgenic ligands, particularly dihydrotestosterone (DHT), from initiating downstream signaling. The compound’s small molecular weight (369.34 g/mol) and high lipophilicity facilitate rapid percutaneous penetration into hair follicles while maintaining extremely low systemic absorption, which distinguishes it from systemic AR antagonists and 5α-reductase inhibitors. This topical selectivity makes RU-58841 a valuable pharmacological tool for androgenetic alopecia (AGA) research and for investigating follicular androgen signaling without systemic endocrine disruption.

Clinical Indications

RU-58841’s local AR antagonism profile supports investigation in the following contexts:

  • Androgenetic Alopecia (AGA): By blocking AR in hair follicle dermal papilla cells, RU-58841 prevents DHT-mediated follicle miniaturization and the progressive shortening of the anagen phase, providing a topical tool for studying androgen-dependent follicle regression in preclinical AGA models.
  • Follicular Androgen Signaling Research: RU-58841 enables selective disruption of follicular androgen signaling without altering circulating testosterone, 5α-reductase activity, or systemic hormonal parameters, making it suitable for mechanistic studies isolating follicular AR-dependent pathways.
  • Comparison with Systemic AR Modulators: As a topically active, non-systemically absorbed comparator, RU-58841 provides a controlled reference against which systemic antiandrogens (e.g., bicalutamide, flutamide) and 5α-reductase inhibitors (e.g., finasteride) can be compared in follicular response studies.

Contraindications

  • Non-validated Human Safety Profile: RU-58841 has not progressed through formal human clinical trials; its safety, systemic exposure at therapeutic topical doses, and long-term tolerability in humans remain uncharacterized.
  • Compromised Skin Barrier: Application to inflamed, abraded, or otherwise compromised skin may significantly increase systemic absorption beyond the intended topical-only profile, potentially producing systemic AR antagonism effects.
  • Sex Steroid-Sensitive Research Models: Although systemic absorption is low under standard conditions, any study requiring a strictly hormone-neutral systemic environment should verify plasma drug levels before concluding topical-only activity.

Mechanism of Action (MOA)

RU-58841 acts as a competitive AR antagonist in the hair follicle microenvironment:

Androgen Receptor Competitive Binding

RU-58841 forms a stable complex with the ligand-binding domain (LBD) of the androgen receptor in hair follicle dermal papilla cells. Its binding constant is substantially lower than that of DHT, providing a competitive advantage in occupying the receptor site and blocking androgen-mediated transcriptional activation.

Follicular Miniaturization Prevention

DHT-activated AR drives the progressive differentiation of hair follicle stem cells toward keratinocyte lineages, shortening anagen phase duration and reducing follicular diameter over successive hair cycles (miniaturization). By blocking this AR signal, RU-58841 interrupts the androgen-driven miniaturization cascade, preserving normal follicle growth cycle kinetics in preclinical AGA models.

Percutaneous Selectivity

RU-58841’s physicochemical profile — low molecular weight (369.34 g/mol) and high lipid solubility — enables rapid penetration through the stratum corneum into the follicular unit. Conversely, the compound undergoes significant first-pass metabolism or binding to dermal proteins, resulting in extremely low systemic plasma levels under normal topical application conditions.

Key Features & Specifications

RU-58841 is characterized by its topical AR antagonism profile and superior follicular selectivity:

AR Kd = 1.8 nM (human) — higher affinity than DHT at follicular AR
Non-steroidal scaffold — no cross-reactivity with estrogen or progesterone receptors
Topical selectivity — minimal systemic absorption under standard conditions
MW 369.34 g/mol — high follicular penetration
No 5α-reductase inhibition — isolated AR-blocking mechanism
5% Topical Solution — SKU L-009

Chemical Analysis

Property Specification Reference Data
IUPAC Name 4-[3-(4-hydroxybutyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
CAS Number 154992-24-2
Molecular Formula C17H18F3N3O3
Molecular Weight 369.34 g/mol
Synonyms PSK-3841; RU58841; HY-10561
Form / Variation 5% Topical Solution (SKU L-009)

Storage, Safety, and Handling

Storage Protocol

Store the 5% topical solution at room temperature (15–25 °C), away from direct sunlight and heat sources. Keep tightly sealed when not in use. The formulation vehicle (typically propylene glycol or ethanol-based) should be checked for phase separation before use; gently mix if settling is observed. Do not freeze the topical solution as vehicle components may crystallize and affect homogeneity.

Handling & Compliance

Wear nitrile gloves during application and handling to prevent unintended dermal exposure. RU-58841 is an AR antagonist; dermal contact by male researchers should be minimized. The compound has not received regulatory approval in any jurisdiction for human therapeutic use. WADA lists compounds with androgenic receptor-modulating properties as potentially subject to prohibition; confirm current regulatory status before initiating studies involving competitive athletes.