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

Journal of Steroid Biochemistry and Molecular Biology

Volumn 109, Issue 1-2, 2008, Pages 129-137

  Piu, Fabrice ^a   Gardell, Luis R ^a   Son, Thomas ^a   Schlienger, Nathalie ^b   Lund, Birgitte W ^b   Schiffer, Hans H ^a   Vanover, Kim E ^a   Davis, Robert E ^a   Olsson, Roger ^b   Bradley, Stefania Risso ^a  

^a ACADIA PHARMACEUTICALS INC   (United States)

^b ACADIA Pharmaceuticals AB   (Sweden)

Author keywords

Non steroidal; Selective androgen receptor modulator

Indexed keywords

AC 262536; SELECTIVE ANDROGEN RECEPTOR MODULATOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; LEVATOR ANI MUSCLE; MALE; NONHUMAN; NUCLEOTIDE SEQUENCE; PROSTATE; RAT; SEMINAL VESICLE;

ANABOLIC AGENTS; ANIMALS; AZABICYCLO COMPOUNDS; BASE SEQUENCE; CELL LINE; DNA PRIMERS; GENES, REPORTER; HUMANS; LIGANDS; MALE; MUSCLES; NAPHTHALENES; ORCHIECTOMY; ORGAN SPECIFICITY; PITUITARY GLAND; PROSTATE; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ANDROGEN; SEMINAL VESICLES; TESTOSTERONE;

ANIMALIA; RATTUS;

EID: 40849102688     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2007.11.001     Document Type: Article

References (26)

1. Nieschlag E. Testosterone treatment comes of age: new options for hypogonadal men. Clin. Endocrinol. (Oxf.) 65 3 (2006) 275-281
2. Basaria S., and Dobs A.S. Risks versus benefits of testosterone therapy in elderly men. Drugs Aging 15 2 (1999) 131-142
3. Hameed A., Brothwood T., and Bouloux P. Delivery of testosterone replacement therapy. Curr. Opin. Investig. Drugs 4 10 (2003) 1213-1219
4. Jockenhovel F. Testosterone supplementation: what and how to give. Aging Male 6 3 (2003) 200-206
5. Oettel M. Testosterone metabolism, dose-response relationships and receptor polymorphisms: selected pharmacological/toxicological considerations on benefits versus risks of testosterone therapy in men. Aging Male 6 4 (2003) 230-256
6. Swerdloff R.S., and Wang C. Androgens and the ageing male. Best Pract. Res. Clin. Endocrinol. Metab. 18 3 (2004) 349-362
7. Rhoden E.L., and Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N. Engl. J. Med. 350 5 (2004) 482-492
8. Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur. Urol. 50 5 (2006) 935-939
9. Davison S.L., and Davis S.R. Androgens in women. J. Steroid Biochem. Mol. Biol. 85 2-5 (2003) 363-366
10. Negro-Vilar A. Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium. J. Clin. Endocrinol. Metab. 84 10 (1999) 3459-3462
11. Cadilla R., and Turnbull P. Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential. Curr. Top. Med. Chem. 6 3 (2006) 245-270
12. Omwancha J., and Brown T.R. Selective androgen receptor modulators: in pursuit of tissue-selective androgens. Curr. Opin. Investig. Drugs 7 10 (2006) 873-881
13. Dalton J.T., Mukherjee A., Zhu Z., Kirkovsky L., and Miller D.D. Discovery of nonsteroidal androgens. Biochem. Biophys. Res. Commun. 244 1 (1998) 1-4
14. Yin D., Xu H., He Y., Kirkovsky L.I., Miller D.D., and Dalton J.T. Pharmacology, pharmacokinetics, and metabolism of acetothiolutamide, a novel nonsteroidal agonist for the androgen receptor. J. Pharmacol. Exp. Ther. 304 3 (2003) 1323-1333
15. Hanada K., Furuya K., Yamamoto N., Nejishima H., Ichikawa K., Nakamura T., Miyakawa M., Amano S., Sumita Y., and Oguro N. Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis. Biol. Pharm. Bull. 26 11 (2003) 1563-1569
16. Miner J.N., Burkett K., Chang W., and Negro-Vilar A. Steroid receptor modulators: approaches to selectivity for androgen receptor. Keystone Symposium on Selective Nuclear Receptor Modulators. Breckenridge, USA (2005)
17. Miner J.N., Chang W., Chapman M.S., Finn P.D., Hong M.H., Lopez F.J., Marschke K.B., Rosen J., Schrader W., Turner R., van Oeveren A., Viveros H., Zhi L., and Negro-Vilar A. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology 148 1 (2007) 363-373
18. Ostrowski J., Kuhns J.E., Lupisella J.A., Manfredi M.C., Beehler B.C., Krystek Jr. S.R., Bi Y., Sun C., Seethala R., Golla R., Sleph P.G., Fura A., An Y., Kish K.F., Sack J.S., Mookhtiar K.A., Grover G.J., and Hamann L.G. 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. Endocrinology 148 1 (2007) 4-12
19. Burstein E.S., Piu F., Ma J.N., Weissman J.T., Currier E.A., Nash N.R., Weiner D.M., Spalding T.A., Schiffer H.H., Del Tredici A.L., and Brann M.R. Integrative functional assays, chemical genomics and high throughput screening: harnessing signal transduction pathways to a common HTS readout. Curr. Pharm. Des. 12 14 (2006) 1717-1729
20. Piu F., Magnani M., and Ader M.E. Dissection of the cytoplasmic domains of cytokine receptors involved in STAT and Ras dependent proliferation. Oncogene 21 22 (2002) 3579-3591
21. Piu F., Gauthier N.K., Olsson R., Currier E.A., Lund B.W., Croston G.E., Hacksell U., and Brann M.R. Identification of novel subtype selective RAR agonists. Biochem. Pharmacol. 71 1-2 (2005) 156-162
22. Piu F., Gauthier N.K., and Wang F. Beta-arrestin 2 modulates the activity of nuclear receptor RAR beta2 through activation of ERK2 kinase. Oncogene 25 2 (2006) 218-229
23. Tan J., Sharief Y., Hamil K.G., Gregory C.W., Zang D.Y., Sar M., Gumerlock P.H., deVere White R.W., Pretlow T.G., Harris S.E., Wilson E.M., Mohler J.L., and French F.S. Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol. Endocrinol. 11 4 (1997) 450-459
24. Poujol N., Lumbroso S., Terouanne B., Lobaccaro J.M., Bourguet W., and Sultan C. Pathophysiology of androgen insensitivity syndromes: molecular and structural approaches of natural and engineered androgen receptor mutations at amino acid 743. J. Clin. Endocrinol. Metab. 87 12 (2002) 5793-5800
25. James A.J., Agoulnik I.U., Harris J.M., Buchanan G., Tilley W.D., Marcelli M., Lamb D.J., and Weigel N.L. A novel androgen receptor mutant, A748T, exhibits hormone concentration-dependent defects in nuclear accumulation and activity despite normal hormone-binding affinity. Mol. Endocrinol. 16 12 (2002) 2692-2705
26. Yin D., Gao W., Kearbey J.D., Xu H., Chung K., He Y., Marhefka C.A., Veverka K.A., Miller D.D., and Dalton J.T. Pharmacodynamics of selective androgen receptor modulators. J. Pharmacol. Exp. Ther. 304 3 (2003) 1334-1340