TAS-108

TAS-108

Clinical data
ATC code	L02BA (WHO)
Identifiers
IUPAC name (1S,9R,10S,11S,14R,15R)-14-(2-{4-[(diethylamino)methyl]-2-methoxyphenoxy}ethyl)-9,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-trien-5-ol
CAS Number	229634-97-3 Citrate: 229634-98-4
PubChem (CID)	9874875 Citrate: CID 9874874
ChemSpider	8050564 Citrate: 8050563
UNII	42U0C8VOLO Citrate: 9B29N23K7E
Chemical and physical data
Formula	C33H47NO3
Molar mass	505.74 g·mol^−1
3D model (Jmol)	Interactive image
SMILES CCN(CC)CC1=CC(=C(C=C1)OCC[C@H]2CC[C@@H]3[C@@]2(CC[C@H]4[C@H]3[C@@H](CC5=C4C=CC(=C5)O)C)C)OC Citrate: CCN(CC)CC1=CC(=C(C=C1)OCC[C@H]2CC[C@@H]3[C@@]2(CC[C@H]4[C@H]3[C@@H](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 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.^[1][2]

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".^[3] 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.^[3]

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.^[3] As of August 2010, the drug had been through five Phase I and two Phase II studies,^[4] and Phase III studies are being planned.^[5]

References

1. 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 ERα 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.
2. "Alumni Hall of Fame 2004: Masato Tanabe". SRI International. Retrieved 2013-02-10.
3. Nielson, Donald (2006). A Heritage of Innovation: SRI's First Half Century. Menlo Park, California: SRI International. pp. 10–15. ISBN 978-0-9745208-1-0.
4. "SRI International to Advance Clinical Development of TAS-108, a Late-Stage Breast Cancer Drug" (Press release). SRI International. Retrieved 2013-02-24.
5. Aman U. Buzdar (January 2005). "TAS-108: A Novel Steroidal Antiestrogen". Clinical Cancer Research. 11 (2): 906s–908s. PMID 15701885.

External links

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