TAS-108

TAS-108

Systematic (IUPAC) name
(7α,17β)-17-(2-{4-[(Diethylamino)methyl]-2-methoxyphenoxy}ethyl)-7-methylestra-1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (1:1)[1]
Identifiers
CAS Number	229634-98-4
ATC code	L02BA
PubChem	CID 9874874
ChemSpider	8050563
Chemical data
Formula	C39H55NO10
Molar mass	697.85
SMILES O=C(O)C(O)(CC(=O)O)CC(=O)O.O(c5cc(ccc5OCC[C@H]3CC[C@H]4[C@H]2[C@@H](c1ccc(O)cc1C[C@H]2C)CC[C@]34C)CN(CC)CC)C
InChI InChI=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 SR16234, 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.^[2][3][4]

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 Institute 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".^[5] 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): SR16234 and SR16287.^[5]

The first of those, SR16234, 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.^[5] As of August 2010, the drug had been through five Phase I and two Phase II studies,^[6][7] and Phase III studies are being planned.^[8]

References

1. "TAS-108". NCI Drug Dictionary. National Cancer Institute. Retrieved 2013-02-24.
2. Yamamoto Y, Wada O, Takada I, Yogiashi Y, Shibata J, Yanagisawa J, Kitazato K, Kato S (December 2003). "Both N- and C-terminal transactivation functions of DNA-bound ERalpha are blocked by a novel synthetic estrogen ligand". Biochem. Biophys. Res. Commun. 312 (3): 656–62. doi:10.1016/j.bbrc.2003.10.178. PMID 14680815.
3. "Alumni Hall of Fame 2004: Masato Tanabe". SRI International. Retrieved 2013-02-10.
4. "Novel Anti-Angiogenic Agents for Breast Cancer Therapy". California Breast Cancer Research Program. Retrieved 2013-02-10.
5. Nielson, Donald (2006). A Heritage of Innovation: SRI's First Half Century. Menlo Park, California: SRI International. pp. 10–13 – 10–15. ISBN 978-0-9745208-1-0.
6. "SRI International to Advance Clinical Development of TAS-108, a Late-Stage Breast Cancer Drug" (Press release). SRI International. Retrieved 2013-02-24.
7. "TAS-108: A Better Anti-Estrogen Drug for Treating Breast Cancer". SRI International. Retrieved 2013-02-24.
8. Buzdar AU (January 2005). "TAS-108: a novel steroidal antiestrogen". Clin. Cancer Res. 11 (2 Pt 2): 906s–8s. PMID 15701885.

External links

• TS 108 at the US National Library of Medicine Medical Subject Headings (MeSH)