Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator

  title={Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator},
  author={Fabrice Piu and Luis R. Gardell and Thomas Son and Nathalie Schlienger and Birgitte W Lund and Hans H. Schiffer and Kimberly E. Vanover and Robert E Davis and Roger Olsson and Stefania Risso Bradley},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  • F. Piu, L. Gardell, S. Bradley
  • Published 1 March 2008
  • Biology, Medicine
  • The Journal of Steroid Biochemistry and Molecular Biology
Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators.
The discovery of ACP-105 (1), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone, is described.
Recent advances in the development of selective androgen receptor modulators
A new class of molecules targeting androgen receptors called selective androgen receptor modulators is being developed, analogous to the clinically successful and at present marketed selective estrogen receptors modulators.
Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator
A novel synthetic androgen receptor ligand, S42, works as a selective androgen receptor modulator and possesses metabolic effects with little impact on the prostate.
Results of the whole-cell binding assay indicated that S42 specifically binds to AR and progesterone receptor, and this effect of S42 was associated with suppression of the SRBP-1c-mediated lipogenic and insulin-desensitizing pathway in the liver and visceral fat.
Deciphering the selective androgen receptor modulators paradigm
The aim of the present paper is to summarize the current standing of research and development of SARMs and plausible molecular mechanisms underlying the potential for selective modulation of androgen receptor (AR) by different ligands and provides an update on SARM discovery paradigms for preclinical evaluations.
Synthesis and biological evaluation of second-generation tropanol-based androgen receptor modulators.
This study has identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.
Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit.
This Award Address attempts to chronicle the landmark discoveries, organize the SARM landscape into clinically relevant bins, and provide insight into the clinical prospects for SARMs.
Recent developments in antiandrogens and selective androgen receptor modulators
Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration.
The aim of this study was to investigate the metabolism of AC-262536 in the horse following in vitro incubation and oral administration to two Thoroughbred horses, in order to identify the most appropriate analytical targets for doping control laboratories.


Pharmacodynamics of Selective Androgen Receptor Modulators
Compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SAR Ms with selective anabolic effects.
Selective androgen receptor modulators: in pursuit of tissue-selective androgens.
SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.
Discovery of nonsteroidal androgens.
These ligands represent the first members of a novel class of androgens with potential therapeutic applications in male fertility and hormone replacement therapy and demonstrate that nonsteroidal ligands can be structurally modified to produce agonist activity.
Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential.
This review provides an overview of current advances in the development of selective androgen receptor modulators (SARMs) and discusses novel, non-steroidal compounds that show tissue selective activity and improved pharmacokinetic properties.
Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats.
The potent oral activity and tissue selectivity exhibited by BMS-564929 are expected to yield a clinical profile that provides the demonstrated beneficial effects of T in muscle and other tissues with a more favorable safety window.
Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium.
  • A. Negro-Vilar
  • Biology, Medicine
    The Journal of clinical endocrinology and metabolism
  • 1999
Significant advances of hormone replacement therapy in postmenopausal females and the expansion and application of HRT to treat and prevent major disorders such as osteoporosis, cardiovascular disease, breast cancer, mood and cognition have clearly established the value of novel HRT therapies for improving women’s health, and by extrapolation, they clearly point out the potential for similar approaches to address men's health disorders.
Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis.
Collectively, this novel compound served as a prototype for SARMs, which had unique tissue selectivity with high potency for bone formation and lower impact upon sex accessory tissues.
An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate.
An androgen receptor (AR) ligand that maintains expected anabolic activities with substantially diminished activity in the prostate and demonstrates the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogenic ligands.
Identification of novel subtype selective RAR agonists.
Pharmacology, Pharmacokinetics, and Metabolism of Acetothiolutamide, a Novel Nonsteroidal Agonist for the Androgen Receptor
The high plasma clearance of acetothiolutamide, due to its extensive hepatic metabolism, likely contributed to its lack of androgenic activity in vivo.