Nonsteroidal tissue selective androgen receptor modulators: a promising class of clinical candidates

Bibliography

• MCNATTY KP, MAKRIS A, DEGRAZIA 0, OSATHANONDH R, RYAN KJ: The production of progesterone, androgens and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro. J. Clin. EndocrinoL Metab. (1979) 49:687–699.
   PubMed Web of Science ®Google Scholar
• FOYE FO, LEMKE TL, WILLIAMS DA: Cholesterol, adrenocorticoids, and sex hormones. In: Principles of Medicinal Chemistry (chapter 23). Brueggenmeier W, Miller DD, Witiak DT (Eds), Williams & Wilkins Publishing (1995):470–471.
   Google Scholar
• GUYTON AC: Reproductive and hormonal functions of the male. In: Textbook of Medical Physiology 8th Edition (chapter 80). WB Saunders Co. (1991):891–894.
   Google Scholar
• WANG C, CUNNINGHAM G, DOBS A et aL: Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J. Clin. EndocrinoL MetaboL (2004) 89:2085–2098.
   PubMed Web of Science ®Google Scholar
• LIAO S, LIANG T, FANG S, CASTANEDA E, SHAG TC: Steroid structure and androgenic activity: specificities involved in the receptor binding and nuclear retention of various androgens. J. Biol. Chem. (1973) 248:6154–6162.
   PubMed Web of Science ®Google Scholar
• JOCKENHOVEL F: Testosterone therapy-what, when and to whom? Aging Male (2004) 7:319–324.
   Google Scholar
• FROST PG, REED MJ, JAMES VH: The aromatization of androstenedione by human adipose and liver tissue. J. Steroid Biochem. (1980) 13:1427–1431.
   PubMedGoogle Scholar
• FANG H, TONG W, BRANHAM WS et aL: Study of 202 natural, synthetic, and environmental ligands for binding to the androgen receptor. Chem. Res. ToxicoL (2003) 16:1338–1358.
   PubMed Web of Science ®Google Scholar
• •Extensive review of ligands that bind to the AR.
   Google Scholar
• CHEN J, KIM J, DALTON JT: Discoveryand therapeutic promise of selective androgen receptor modulators. MoL Interv. (2005) 5:173–188.
   PubMed Web of Science ®Google Scholar
• DALTON JT, MUKHERJEE A, ZHU Z, KIRKOVSKY L, MILLER DD: Discovery of nonsteroidal androgens. Biochem. Biophys. Res. Comm. (1998) 244:1–4.
   PubMed Web of Science ®Google Scholar
• ••First report of an AR agonist (in vitro).
   Google Scholar
• YIN, D, XU H, HEY, KIRKOVSKY LI, MILLER DD, DALTON JT: Pharmacology, pharmacokinetics, and metabolism of acetothiolutamide, a novel nonsteroidal agonist of the androgen receptor. J. PharmacoL Exp. Ther. (2003) 304:1323–1333.
   PubMed Web of Science ®Google Scholar
• MARHEFKA CA, GAO W, CHUNG KW et al.: Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators. J. Med. Chem. (2004) 47:993–998.
   PubMed Web of Science ®Google Scholar
• ••First metabolically stable in vivopropionanilide SARNI agonists.
   Google Scholar
• YIN D, HE Y, PERERA MA et ell.: Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor. Molec. PharmacoL (2003) 63:211–223.
   Google Scholar
• HEY, YIN D, PEREIRA M et al.: Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor. Eur. J. Med. Chem. (2002) 37:619–634.
   PubMed Web of Science ®Google Scholar
• KIRKOVSKY L, MUKHERJEE A, YIN D, DALTON JT, MILLER DD: Chiral nonsteroidal affinity ligands for the androgen receptor. 1. Bicalutamide analogues bearing electrophilic groups in the b aromatic ring. J. Med. Chem. (2000) 43:581–590.
   Google Scholar
• ZHI L, TEGLEY CM, MARSCHKE KB, JONES TK: Switching androgen receptor antagonists to agonists by modifying C-ring substituents on piperidino [3,2-g]quinolinone. Bioorg. Med. Chem. Lett. (1999) 9:1009–1012.
   PubMed Web of Science ®Google Scholar
• HANIANN LG, MANI NS, DAVIS RL, WANG XN, MARSCHKE KB, JONES TK: Discovery of a potent, orally active, nonsteroidal androgen receptor agonist: 4-ethy1-1,2,3,4-tetrahydro-6-(trifluoromethyl)-8-pyridono [5,6-0 - quinoline (LG121071). J. Med. Chem. (1999) 42:210–212.
   PubMed Web of Science ®Google Scholar
• HIGUCHI RI, EDWARDS: JP, CAFERRO TR et aL: 4-Alkyl- and 3,4-dialky1-1,2,3,4-tetrahydro-8-pyridono [5,6-g] quinolines: potent, nonsteroidal androgen receptor agonists. Bioorg. Med. Chem. Lett. (1999) 9:1335–1340.
   PubMed Web of Science ®Google Scholar
• EDWARDS JP, HIGUCHI RI, WINN DT et al.: Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)-2H-pyranol3,2-glquinolin-2-one. Bioorg Med. Chem. Lett. (1999) 9:1003–1008.
   PubMed Web of Science ®Google Scholar
• VAN DORT ME, ROBINS DM, WAYBURN B: Design, synthesis, and pharmacological characterization of 4-44,4-dimethy1-3-(4-hydroxybuty1)-5-oxo-2-thioxo-1-imiciazolidinyll-2-iodobenzonitrile as a high-affinity nonsteroidal androgen receptor ligand. J Med. Chem. (2000) 43:3344–3347.
   PubMed Web of Science ®Google Scholar
• DUKES MFB, HUGHES LR, TUCKER H: WOODBURN JR: Nonsteroidal progestins and antiprogestins related to flutamide. Steroids (2000) 65:725–731.
   PubMed Web of Science ®Google Scholar
• HANADA K, FURUYA K, YANIANIOTO N et aL: Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARNI), in rat models of osteoporosis. Biol. Pharm. Bull. (2003) 26:1563–1569.
   PubMed Web of Science ®Google Scholar
• •Discusses osteoanabolic activity of Kaken's tetrahydroquinoline, S-40503.
   Google Scholar
• BURDEN PM, Al TH, LIN HQ et al.: Chiral derivatives of 2-cyclohexylideneperhydro-4,7-methanoindenes, a novel class of nonsteroidal androgen receptor ligand: synthesis, X-ray analysis, and biological activity. J. Med. Chem. (2000) 43:4629–4635.
   PubMed Web of Science ®Google Scholar
• SALVATI ME, BALOG A. WEI DD et aL:Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus. Bioorg. Med. Chem. Lett. (2005) 15:389–393.
   PubMed Web of Science ®Google Scholar
• SALVATI ME, BALOG A. SHAN Wet al.: Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists. Bioorg. Med. Chem. Lett. (2005) 15:271–276.
   Google Scholar
• NEGRO-VILAR A: Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium. J. Clin. Endocrinol. MetaboL (1999) 84:3459–3462.
   PubMed Web of Science ®Google Scholar
• •Concise and informative review of potential SARNI uses.
   Google Scholar
• KALLIO PJ, JANNE OA, PALVIMO JJ: Agonists, but not antagonists, alter the conformation of the hormone-binding domain of androgen receptor. Endocrinology (1994) 134:998–1001.
   PubMed Web of Science ®Google Scholar
• KUIL CW, BERREVOETS CA, MULDER E: Ligand-induced conformational alterations of the androgen receptor analyzed by limited trypsinization-studies on the mechanism of antiandrogen action. J. Biol. Chem. (1995) 270:27569–27576.
   PubMed Web of Science ®Google Scholar
• LE HT, SCHALDACH CM, FIRSTONE GL, BJELDANES LF: Plant-derived 3,3'-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J. Biol. Chem. (2003) 278:21136–21145.
   PubMed Web of Science ®Google Scholar
• BURNS KH, AGNO JE, CHEN L et al: Sexually dimorphic roles of steroid hormone receptor signaling in gonad tumourigenesis. Mol. Endocrinol (2003) 17:2039–2052.
   PubMedGoogle Scholar
• GAO W, KEARBEY JD, NAIR VA et ell.: Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5a-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology (2004) 145:5420–5428.
   Google Scholar
• ANDRIOLE G, BRUCHOVSKY N, CHUNG LW et al.: Dihydrotestosterone and the prostate: the scientific rationale for 5a-reductase inhibitors in the treatment of benign prostatic hyperplasia. J. Urol. (2004) 172:1399–1403.
   PubMed Web of Science ®Google Scholar
• THOMPSON IM, GOODMAN PJ, TANGEN CM et al: The influence of finasteride on the development of prostate cancer. N Engl. J. Med. (2003) 349:215–224.
   PubMed Web of Science ®Google Scholar
• BASARIA S, DOBS AS: New modalities oftransdermal testosterone replacement. Treat. Endocrinol (2003) 2:1–9.
   PubMedGoogle Scholar
• JOCKENHOVEL F: Testosterone supplementation: what and how to give. Aging Male (2003) 6:200–206.
   PubMedGoogle Scholar
• VELDHUIS JD, KEENAN DM, IRANMANESH A: Mechanisms of ensemble failure of the male gonadal axis in aging. J. Endocrinol Invest. (2005) 28:8–13.
   PubMedGoogle Scholar
• LUND BC, BEVER-STILLE KA, PERRY PJ: Testosterone and andropause: the feasibility of testosterone replacement therapy in elderly men. Pharmacotherapy (1999) 19:951–956.
   PubMed Web of Science ®Google Scholar
• MORETTI C, FRAJESE GV, GUCCIONE Let al.: Androgens and body composition in the aging male. J . Endocrinol Invest. (2005) 28:56–64.
   Google Scholar
• WOLF OT: Cognitive functions and sex steroids. Ann. Endocrinol (2003) 64:158–161.
   PubMed Web of Science ®Google Scholar
• HIJAZI RA, CUNNINGHAM GR: Andropause: is androgen replacement therapy indicated for the aging male? Ann. Rev. Med. (2005) 56:117–137.
   Google Scholar
• JUUL A, SKAKKEBAEK NE: Androgens and the ageing male. Hum. Reprod.Update (2002) 8:423–433.
   PubMed Web of Science ®Google Scholar
• TENOVER JL: Testosterone and the aging male. J. Androl (1997) 18:103–106.
   PubMed Web of Science ®Google Scholar
• LUND BC, BEVER-STILLE KA, PERRY PJ: Testosterone and andropause: the feasibility of testosterone replacement therapy in elderly men. Pharmacotherapy (1999) 19:951–956.
   PubMed Web of Science ®Google Scholar
• EASTELL, R. Treatment of postmenopausal osteoporosis. N Engl. J. Med. (1998) 338:736–746.
   PubMed Web of Science ®Google Scholar
• AMIN S: Male osteoporosis: epidemiology and pathophysiology. Curr. Osteoporos. Rep. (2003) 1:71–77.
   PubMedGoogle Scholar
• TANAKA Y, NAKAYAMADA S, OKADAY: Osteoblasts and osteoclasts in bone remodeling and inflammation. Cuff. Drug Targets Inflamm. Allergy (2005) 4:325–328.
   PubMedGoogle Scholar
• GREENBLATT D: Treatment of postmenopausal osteoporosis. Pharmacotherapy (2005) 25:574–584.
   PubMed Web of Science ®Google Scholar
• SHRADER SP, RAGUCCI KR: Parathyroid hormone (1-84) and treatment of osteoporosis. Ann. Pharmacother. (2005) 39:1511–1516.
   PubMed Web of Science ®Google Scholar
• KAMEL HK, MAAS D, DUTHIE EH JR: Role of hormones in the pathogenesis and management of sarcopenia. Drugs Aging (2002) 19:865–877.
   PubMed Web of Science ®Google Scholar
• NARICI MV, REEVES ND, MORSE CI, MAGANARIS CN: Muscular adaptations to resistance exercise in the elderly. Musculoskelet. Neuronal Interact. (2004) 4:161–164.
   PubMedGoogle Scholar
• LEVEILLE SG: Musculoskeletal aging. Curr. Opin. Rheumatol (2004) 16:114–118.
   PubMed Web of Science ®Google Scholar
• BAUMGARTNER RN, KOEHLER KM, GALLAGHER D et al.: Epidemiology of sarcopenia among the elderly in New Mexico. Am. J. Epidemiol. (1998) 147:755–763
   PubMed Web of Science ®Google Scholar
• MUHLBERG W, SIEBER C: Sarcopenia and frailty in geriatric patients: implications for training and prevention. Z. Gerontol Geriatr. (2004) 37:2–8.
   PubMed Web of Science ®Google Scholar
• LYNCH GS: Emerging drugs for sarcopenia: age-related muscle wasting. Expert Opin. Emerg. Drugs (2004) 9:345–361.
   PubMedGoogle Scholar
• •Good overview of this field.
   Google Scholar
• HERBST KL, BHASIN S: Testosterone action on skeletal muscle. Curr. Opin. Clin. Num Metab. Care (2004) 7:271–277.
   PubMed Web of Science ®Google Scholar
• KARAGIANNIS A, HARSOULIS F: Gonadal dysfunction in systemic diseases. Eur. J. Endocrinol. (2005) 152:501–513.
   PubMed Web of Science ®Google Scholar
• GAO W REISER PJ, COSS CC et al.: Selective androgen receptor modulator (SARM) treatment improves muscle strength and body composition, and prevents bone loss in orchidectomized rats. Endocrinology (11 August 2005) Epub ahead of print.
   Google Scholar
• PRNewswire: First Call press release from GTx, Inc., 3 N. Dunlap St., Memphis, TN, USA (7 September 2005) 38163.
   Google Scholar
• GERVASIO JM, DICKERSON RN, SWEARINGEN Jet al.: Oxandrolone in trauma patients. Pharmacotherapy (2000) 20:1328–1334.
   Google Scholar
• DEMLING RH, ORGILL DP: The anticatabolic and wound healing effects of the testosterone analogue oxandrolone after severe burn injury. J. Crit. Care (2000) 15:12–17.
   PubMed Web of Science ®Google Scholar
• STRAWFORD A, BARBIERI T, VAN LOAN M et al.: Resistance exercise and supraphysiologic androgen therapy in eugonadal men with HIV-related weight loss: a randomized controlled trial. /AMA (1999) 281:1282–1290.
   Google Scholar
• PEETS EA, HENSON MF, NERI R: On the mechanism of the anti-androgenic action of flutamide (a,a,a-trifluoro-2-methyl-4'-nitro-m-propionotoluidide) in the rat. Endocrinology (1974) 94:532–540.
   PubMed Web of Science ®Google Scholar
• CLARK CR, MERRY BJ, NOWELL NW: Effect of a,a,a-trifluoro-2-methyl-4'-nitro-m-lactotoluidide (Sch 16423) on serum testosterone and LH in rats. J. Reprod. Fend (1981) 61:189–191.
   PubMed Web of Science ®Google Scholar
• MUKHERJEE A. KIRKOVSKY L, YAO XT, YATES RC, MILLER DD, DALTON JT: Enantioselective binding of Casodex to the androgen receptor. Xenobiotica (1996) 26:117–122.
   PubMed Web of Science ®Google Scholar
• NAIR VA, MUSTAFA SM, MOHLER ML et al: Synthesis of irreversibly binding bicalutamide analogues for imaging studies. Tet. Lett. (2005) 46:4821–4823.
   PubMed Web of Science ®Google Scholar
• BOHL CE, CHANG C, MOHLER ML et al: A ligand-based approach to identify quantitative structure-activity relationships for the androgen receptor. J. Med. Chem. (2004) 47:3765–3776.
   PubMed Web of Science ®Google Scholar
• LAWSON Mk LI D, GLIDEWELL -KINNEY CA, LOPEZ FJ: Androgen responsiveness of the pituitary gonadotrope cell line LfT2. J. EndocrinoL (2001) 170:601–607.
   PubMed Web of Science ®Google Scholar
• Press release quoted in Chemical Business News.
   Google Scholar
• LEVINSON DJ, DECKER DE: Characterization of a l3FIlmethyltrienolone (R1881) binding protein in rat liver cytosol. J . Steroid Biochem. (1985) 22:211–219.
   PubMedGoogle Scholar
• SALVATI ME, BALOG A, ATTAR R, GOTTARDIS M, KRYSTEK S JR, RAMPULLA R: Design of a novel series of [2.2.11-oxobicyclo based androgen receptor antagonists with an unique pharmacological profile. Medicinal Chemistry Division abstract 239 presented at the Nuclear Hormone Receptors Symposium. 230th ACS National Meeting. Washington, DC (29 August 2005).
   Google Scholar
• MINER JN: Oral presentation at the Tissue-Selective Nuclear Receptor Symposia, Keystone Meeting, Breckenridge, CO, USA (21 September, 2005).
   Google Scholar
• ROSEN J, NEGRO-VILAR A: Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. MusculoskeL Neuron. Interact. (2002) 2:222–224.
   PubMedGoogle Scholar
• BOHL CE, GAO W, MILLER DD, BELL CE, DALTON JT: Structural basis for antagonism and resistance of bicalutamide in prostate cancer. Proc. Natl. Acad. Sci. USA (2005) 102:6201–6206.
   PubMed Web of Science ®Google Scholar
• BOHL CE, MILLER DD, CHEN J, BELL CE, DALTON JT : Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. J. Biol. Chem. (29 August 2005) Epub ahead of print.
   Google Scholar