TAS-108 - Misplaced Pages

Chemical compound

Pharmaceutical compound

TAS-108
Clinical data

Other names	17β--2-methoxyphenoxy]ethyl]-7α-methylestra-1,3,5(10)-trien-3-ol; 17β--2-methoxyphenoxy]ethyl]-7α-methylestradiol
Routes of administration	By mouth
ATC code	L02BA (WHO)
Identifiers
IUPAC name (1S,9R,10S,11S,14R,15R)-14-(2-{4--2-methoxyphenoxy}ethyl)-9,15-dimethyltetracycloheptadeca-2(7),3,5-trien-5-ol
CAS Number	229634-97-3 Citrate: 229634-98-4
PubChem CID	9874875 Citrate: 9874874
ChemSpider	8050564 Citrate: 8050563
UNII	42U0C8VOLO Citrate: 9B29N23K7E
CompTox Dashboard (EPA)	DTXSID601117925
Chemical and physical data
Formula	C₃₃H₄₇NO₃
Molar mass	505.743 g·mol
3D model (JSmol)	Interactive image Citrate: Interactive image
SMILES CCN(CC)CC1=CC(=C(C=C1)OCC2CC32(CC43(CC5=C4C=CC(=C5)O)C)C)OC Citrate: CCN(CC)CC1=CC(=C(C=C1)OCC2CC32(CC43(CC5=C4C=CC(=C5)O)C)C)OC.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
InChI InChI=1S/C33H47NO3/c1-6-34(7-2)21-23-8-13-30(31(19-23)36-5)37-17-15-25-9-12-29-32-22(3)18-24-20-26(35)10-11-27(24)28(32)14-16-33(25,29)4/h8,10-11,13,19-20,22,25,28-29,32,35H,6-7,9,12,14-18,21H2,1-5H3/t22-,25-,28-,29+,32-,33-/m1/s1 Key:OHCPNHFLPCVWRG-MWSJHZLTSA-N Citrate: InChI=1S/C33H47NO3.C6H8O7/c1-6-34(7-2)21-23-8-13-30(31(19-23)36-5)37-17-15-25-9-12-29-32-22(3)18-24-20-26(35)10-11-27(24)28(32)14-16-33(25,29)4;7-3(8)1-6(13,5(11)12)2-4(9)10/h8,10-11,13,19-20,22,25,28-29,32,35H,6-7,9,12,14-18,21H2,1-5H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t22-,25-,28-,29+,32-,33-;/m1./s1 Key:VOHOCSJONOJOSD-SCIDSJFVSA-N

TAS-108, also known as SR-16234, is a drug discovered by Masato Tanabe and under development by SRI International and Taiho Pharmaceutical. It is a steroid hormone that has shown signs of treating and preventing breast cancer, even in patients where tamoxifen has failed.

Development

Masato Tanabe's team at SRI has focused on the development of steroid hormones. A compound discovered in a previous SRI contract from the National Institutes of Health showed potential – it acted like "anti-estrogen" in the breasts and uterus but like normal estrogen elsewhere in the body, and was more "tissue-selective". A contract was proposed to Taiho Pharmaceutical in July 1996, and within six years and slightly under $3 million (an unusually short amount of time), two new drugs were discovered and tested on people (particularly people for which tamoxifen has failed): SR-16234 and SR-16287.

The first of those, SR-16234, also inhibited the growth of blood vessels angiogenesis and accelerated the death of cancer cells apoptosis and thus was particularly well suited to be an anti-cancer drug. As of August 2010, the drug had been through five Phase I and two Phase II studies, and Phase III studies are being planned.

References

Yamamoto Y, Shibata J, Yonekura K, Sato K, Hashimoto A, Aoyagi Y, et al. (January 2005). "TAS-108, a novel oral steroidal antiestrogenic agent, is a pure antagonist on estrogen receptor alpha and a partial agonist on estrogen receptor beta with low uterotrophic effect". Clinical Cancer Research. 11 (1): 315–322. doi:10.1158/1078-0432.315.11.1. PMID 15671561.
Yamamoto Y, Wada O, Takada I, Yogiashi Y, Shibata J, Yanagisawa J, et al. (December 2003). "Both N- and C-terminal transactivation functions of DNA-bound ERalpha are blocked by a novel synthetic estrogen ligand". Biochemical and Biophysical Research Communications. 312 (3): 656–662. doi:10.1016/j.bbrc.2003.10.178. PMID 14680815.
"Alumni Hall of Fame 2004: Masato Tanabe". SRI International. Retrieved 2013-02-10.
^ Nielson D (2006). A Heritage of Innovation: SRI's First Half Century. Menlo Park, California: SRI International. pp. 10–15. ISBN 978-0-9745208-1-0.
"SRI International to Advance Clinical Development of TAS-108, a Late-Stage Breast Cancer Drug" (Press release). SRI International. Retrieved 2013-02-24.
Buzdar AU (January 2005). "TAS-108: a novel steroidal antiestrogen". Clinical Cancer Research. 11 (2 Pt 2): 906s – 908s. doi:10.1158/1078-0432.906s.11.2. PMID 15701885.

External links

SR-16234 (TAS-108) - AdisInsight
TS 108 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Estrogen receptor modulators

ERTooltip Estrogen receptor

Agonists

Unknown/unsorted: ERB-26
ERA-45
ERB-79
ZK-283197

Xenoestrogens: Anise-related (e.g., anethole, anol, dianethole, dianol, photoanethole)
Chalconoids (e.g., isoliquiritigenin, phloretin, phlorizin (phloridzin), wedelolactone)
Coumestans (e.g., coumestrol, psoralidin)
Flavonoids (incl. 7,8-DHF, 8-prenylnaringenin, apigenin, baicalein, baicalin, biochanin A, calycosin, catechin, daidzein, daidzin, ECG, EGCG, epicatechin, equol, formononetin, glabrene, glabridin, genistein, genistin, glycitein, kaempferol, liquiritigenin, mirificin, myricetin, naringenin, penduletin, pinocembrin, prunetin, puerarin, quercetin, tectoridin, tectorigenin)
Lavender oil
Lignans (e.g., enterodiol, enterolactone, nyasol (cis-hinokiresinol))
Metalloestrogens (e.g., cadmium)
Pesticides (e.g., alternariol, dieldrin, endosulfan, fenarimol, HPTE, methiocarb, methoxychlor, triclocarban, triclosan)
Phytosteroids (e.g., digitoxin (digitalis), diosgenin, guggulsterone)
Phytosterols (e.g., β-sitosterol, campesterol, stigmasterol)
Resorcylic acid lactones (e.g., zearalanone, α-zearalenol, β-zearalenol, zearalenone, zeranol (α-zearalanol), taleranol (teranol, β-zearalanol))
Steroid-like (e.g., deoxymiroestrol, miroestrol)
Stilbenoids (e.g., resveratrol, rhaponticin)
Synthetic xenoestrogens (e.g., alkylphenols, bisphenols (e.g., BPA, BPF, BPS), DDT, parabens, PBBs, PHBA, phthalates, PCBs)
Others (e.g., agnuside, rotundifuran)

Mixed
(SERMsTooltip Selective estrogen receptor modulators)

Antagonists

Coregulator-binding modulators: ERX-11

Noncompetitive inhibitors: Trilostane

GPERTooltip G protein-coupled estrogen receptor

Agonists	2-Methoxyestradiol 7β-Hydroxyepiandrosterone Afimoxifene (4-hydroxytamoxifen) Aldosterone Atrazine Bisphenol A Daidzein DDT (p,p'-DDT, o',p'-DDE) Diarylpropionitrile Equol Estradiol Ethinylestradiol Fulvestrant (ICI-182780) G-1 Genistein GPER-L1 GPER-L2 Hydroxytyrosol Kepone Nicotinic acid Nicotinamide Nonylphenol Oleuropein PCBs (2,2',5'-PCB-4-OH) Propylpyrazoletriol Quercetin Raloxifene Resveratrol STX Tamoxifen Tectoridin
Antagonists	CCL18 Estriol G-15 G-36 MIBE
Unknown	Diethylstilbestrol Zearalenone

See also: Receptor/signaling modulators; Estrogens and antiestrogens; Androgen receptor modulators; Progesterone receptor modulators; List of estrogens

Categories:

Development

See also

References

External links