Skip to main content Accessibility help
×
Home
  • Print publication year: 2012
  • Online publication date: August 2012

Chapter 21 - The state-of-the-art in the development of selective androgen receptor modulators

21.10 References

BasariaS, CollinsL, DillonEL, OrwollK, StorerTW, MiciekR, UlloorJ, ZhangA, EderR, ZientekH, GordonG, KazmiS, Sheffield-MooreM, BhasinS (2012) The safety, pharmacokinetics, and the effects of LGD-4033, a novel non-steroidal oral, selective androgen receptor modulator (SARM), in healthy young men. J Gerontol A Biol Sci Med Sci; in press
BhasinS, JasujaR (2009) Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care 12:232–240
BhasinS, CalofOM, StorerTW, LeeML, MazerNA, JasujaR, MontoriVM, GaoW, DaltonJT (2006) Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab 2:146–159
BohlCE, WuZ, MillerDD, BellCE, DaltonJT (2007) Crystal structure of the T877A human androgen receptor ligand-binding domain complexed to cyproterone acetate provides insight for ligand-induced conformational changes and structure-based drug design. J Biol Chem 282:13648–13655
DaltonJT, MukherjeeA, ZhuZ, KirkovskyL, MillerDD (1998) Discovery of nonsteroidal androgens. Biochem Biophys Res Commun 244:1–4
DimickDF, HeronM, BaulierEE, JayleeMF (1961) A comparative study of the metabolic fate of testosterone, 17 alpha-methyl-testosterone. 19-nor-testosterone. 17 alpha-methyl-19-nor-testosterone and 17 alpha-methylestr-5(10)-ene-17 beta-ol-3-one in normal males. Clin Chim Acta 6:63–71
EdwardsJP, WestSJ, PooleyCL, MarschkeKB, FarmerLJ, JonesTK (1998) New nonsteroidal androgen receptor modulators based on 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g] quinolinone. Bioorg Medl Chem Lett 8:745–750
FragkakiAG, AngelisYS, KoupparisM, Tsantili-KakoulidouA, KokotosG, GeorgakopoulosC (2009) Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure. Steroids 74:172–197
GaoW, ReiserPJ, KearbeyJD, PhelpsMA, CossCC, MillerDD, DaltonJT (2004a) Effects of Novel Selective Androgen Receptor Modulator (SARM) on Skeletal Muscle Mass and Strength in Castrated Male Rats. The Endocrine Society, New Orleans
GaoW, KearbeyJD, NairVA, ChungK, ParlowAF, MillerDD, DaltonJT (2004b) Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology 145:5420–5428
GaoW, ReiserPJ, CossCC, PhelpsMA, KearbeyJD, MillerDD, DaltonJT (2005) Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology 146:4887–4897
HamannLG (2004) Discovery and preclinical profile of a highly potent and muscle selective androgen receptor modulator (SARM). 227th National Meeting of the American Chemical Society Medicinal Chemistry Division, March 28–April 1, Anaheim, CA
HamannLG, ManiNS, DavisRL, WangXN, MarschkeKB, JonesTK (1999) Discovery of a potent, orally active, nonsteroidal androgen receptor agonist: 4-ethyl-1,2,3,4-tetrahydro-6-(trifluoromethyl)-8-pyridono[5,6-g]-quinoline (LG121071). J Med Chem 42:210–212
HamannLG, ManfrediMC, SunC, KrystekSR Jr, HuangY, BiY, AugeriDJ, WangT, ZouY, BetebennerDA, FuraA, SeethalaR, GollaR, KuhnsJE, LupisellaJA, DarienzoCJ, CusterLL, PriceJL, JohnsonJM, BillerSA, ZahlerR, OstrowskiJ (2007) Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators. Bioorg Medl Chem Lett 17:1860–1864
HanadaK, FuruyaK, YamamotoN, NejishimaH, IchikawaK, NakamuraT, MiyakawaM, AmanoS, SumitaY, OguroN (2003) Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis. Biol Pharm Bull 26:1563–1569
HartsookEW, HershbergerTV (1961) Effect of synthetic steroid or phenanthrene compounds upon weight gain and feed efficiency of rats. ProcSocExp Biol Med 106:57–60
HeY, YinD, PereraM, KirkovskyL, StourmanN, LiW, DaltonJT, MillerDD (2002) Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor. Eur J Med Chem 37:619–634
HeinleinCA, ChangC (2002) Androgen receptor (AR) coregulators: an overview. Endocr Rev 23:175–200
HiguchiRI, ArientiKL, LopezFJ, ManiNS, MaisDE, CaferroTR, LongYO, JonesTK, EdwardsJP, ZhiL, SchraderWT, Negro-VilarA, MarschkeKB (2007) Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. J Med Chem 50:2486–2496
HoffmanJR, KraemerWJ, BhasinS, StorerT, RatamessNA, HaffGG, WilloughbyDS, RogolAD (2009) Position stand on androgen and human growth hormone use. J Strength Cond Res 23(5 Suppl):S1–S59
JasujaS, UlloorJ, YengoCM, ChoongK, IstominAY, LivesayDR, JacobsDJ, SwerdloffRS, MikšovskáJ, LarsenRW, BhasinS (2009) Kinetic and thermodynamic characterization of DHT-induced conformational perturbations in androgen receptor ligand binding domain. Mol Endocrinol 23:1231–1241
KearbeyJD, GaoW, NarayananR, FisherSJ, WuD, MillerDD, DaltonJT (2007) Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. Pharm Res 24:328–335
KumarN, DidolkarAK, MonderC, BardinCW, SundaramK (1992) The biological activity of 7 alpha-methyl-19-nortestosteroneis not amplified in male reproductive tract as is that of testosterone. Endocrinology 130:3677–3683
ManfrediMC, BiY, NirschlAA, SuttonJC, SeethalaR, GollaR, BeehlerBC, SlephPG, GroverGJ, OstrowskiJ, HamannLG (2007) Synthesis and SAR of tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues as highly potent selective androgen receptor modulators. Bioorg Medl Chem Lett 17:4487–4490
MasielloD, ChenSY, XuY, VerhoevenMC, ChoiE, HollenbergAN, BalkSP (2004) Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells. Mol Endocrinol 18:2388–2401
MinerJN, ChangW, ChapmanMS, FinnPD, HongMH, LopezFJ, MarschkeKB, RosenJ, SchraderW, TurnerR, van OeverenA, ViverosH, ZhiL, Negro-VilarA (2007) An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology 148:363–373
MuradF, HaynesRC (1980) Androgens and anabolic steroids. In: GoodmanL, GilmanA (eds) The Pharmacological Basis of Therapeutics, 6th edn. McMilan Press, New York, pp 1448–1465
NarayananR, MohlerML, BohlCE, MillerDD, DaltonJT (2008) Selective androgen receptor modulators in preclinical and clinical development. Nucl Recept Signal 6:e010
NgRA, LanterJC, AlfordVC, AllanGF, SbrisciaT, LundeenSG, SuiZ (2007) Synthesis of potent and tissue-selective androgen receptor modulators (SARMs): 2-(2,2,2)-trifluoroethyl-benzimidazole scaffold. Bioorg Medl Chem Lett 17:1784–1787
OstrowskiJ, KuhnsJE, LupisellaJA, ManfrediMC, BeehlerBC, KrystekSR Jr, BiY, SunC, SeethalaR, GollaR, SlephPG, FuraA, AnY, KishKF, SackJS, MookhtiarKA, GroverGJ, HamannLG (2007) 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 148:4–12
RosenJ, Negro-VilarA (2002) Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. J Musculoskelet Neuronal Interact 2:222–224
RussellDW, WilsonJD (1994) Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem 63:25–61
SathyaG, ChangCY, KazminD, CookCE, McDonnellDP (2003) Pharmacological uncoupling of androgen receptor-mediated prostate cancer cell proliferation and prostate-specific antigen secretion. Cancer Res 63:8029–8036
SchmidtA, HaradaS-I, KimmelDB, BaiC, ChenF, RutledgeSJ, VogelRL, SccafonasA, GentileMA, NantermetPV, McElwee-WitmerS, PennypackerB, MassarachiaP, SahooSP, KimY, MeissnerRS, HartmanGD, DugganME, RodanGA, TowlerDA, RayWJ (2009) Identification of anabolic selective androgen receptor modulators with reduced activities in the reproductive tissues and sebaceous glands. J Biol Chem 284:36367–36376
SnyderPJ, LawrenceDA (1980) Treatment of male hypogonadism withtestosterone enanthate. J Clin Endocrinol Metab 51:1335–1339
SokolRZ, PalaciosA, CampfieldLA, SaulC, SwerdloffRS (1982) Comparison of the kinetics of injectable testosterone in eugonadal and hypogonadal men. Fertil Steril 37:425–430
SongLN, HerrellR, ByersS, ShahS, WilsonEM, GelmannEP (2003) Beta-catenin binds to the activation function 2 region of the androgen receptor and modulates the effects of the N-terminal domain and TIF2 on ligand-dependent transcription. Mol Cell Biol 23:1674–1687
SundaramK, KumarN, BardinCW (1994) 7 alpha-methyl-19-nortestosterone: an ideal androgen for replacement therapy. Recent Prog Horm Res 49:373–376
van OeverenA, MotamediM, ManiNS, MarschkeKB, LopezFJ, SchraderWT, Negro-VilarA, ZhiL (2006) Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino-4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator. J Med Chem 49:6143–6146
van OeverenA, MotamediM, MartinboroughE, ZhaoS, ShenY, WestS, ChangW, KallelA, MarschkeKB, LopezFJ, Negro-VilarA, ZhiL (2007) Novel selective androgen receptor modulators: SAR studies on 6-bisalkylamino-2-quinolinones. Bioorg Med Chem Lett 17:1527–1531
YinD, GaoW, KearbeyJD, XuH, ChungK, HeY, MarhefkaCA, VeverkaKA, MillerDD, DaltonJT (2003a) Pharmacodynamics of selective androgen receptor modulators. J Pharmacol Exp Ther 304:1334–1340
YinD, HeY, PereraMA, HongSS, MarhefkaC, StourmanN, KirkovskyL, MillerDD, DaltonJT (2003b) Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor. Mol Pharmacol 63:211–223
ZacharovMN, PillaiBK, BhasinS, UlloorJ, IstominAY, GuoC, GodzikA, KumarR, JasujaR (2011)) Dynamics of coregulator-induced conformational perturbations in androgen receptor ligand binding domain. Mol Cell Endocrinol 341:1–8