TAS-108

TAS-108
Clinical data
Other names	17β-4-(diethylamino)methyl-2-methoxyphenoxyethyl-7α-methylestra-1,3,5(10)-trien-3-ol; 17β-2-4-(diethylamino)methyl-2-methoxyphenoxyethyl-7α-methylestradiol
Routes of; administration	By mouth
ATC code	L02BA (WHO) ;
Identifiers
	IUPAC name (1S,9R,10S,11S,14R,15R)-14-(2-{4-(diethylamino)methyl-2-methoxyphenoxy}ethyl)-9,15-dimethyltetracyclo8.7.0.02,7.011,15heptadeca-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−1
3D model (JSmol)	Interactive image; Citrate: Interactive image;
	SMILES CCN(CC)CC1=CC(=C(C=C1)OCCC@H2CCC@@H3C@@2(CCC@H4C@H3C@@H(CC5=C4C=CC(=C5)O)C)C)OC; ; Citrate: CCN(CC)CC1=CC(=C(C=C1)OCCC@H2CCC@@H3C@@2(CCC@H4C@H3C@@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 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.^[2]^[3]

Developmentedit

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".^[4] 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.^[4]

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.^[4] As of August 2010, the drug had been through five Phase I and two Phase II studies,^[5] and Phase III studies are being planned.^[6]

Referencesedit

^ 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.
^ ^a ^b ^c 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 linksedit

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

Zdroj:https://en.wikipedia.org?pojem=TAS-108
Text je dostupný za podmienok Creative Commons Attribution/Share-Alike License 3.0 Unported; prípadne za ďalších podmienok. Podrobnejšie informácie nájdete na stránke Podmienky použitia.

[Yamamoto_Shibata_Yonekura_Sato_2005_pp._315–322-1] 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.

[pmid14680815-2] 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.

[hof-3] "Alumni Hall of Fame 2004: Masato Tanabe". SRI International. Retrieved 2013-02-10.

[nielson-4] 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.

[5] "SRI International to Advance Clinical Development of TAS-108, a Late-Stage Breast Cancer Drug" (Press release). SRI International. Retrieved 2013-02-24.

[pmid15701885-6] 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.

[1]

[2]

[3]

[4]

[5]

[6]

Clinical data

Other names	17β-4-(diethylamino)methyl-2-methoxyphenoxyethyl-7α-methylestra-1,3,5(10)-trien-3-ol; 17β-2-4-(diethylamino)methyl-2-methoxyphenoxyethyl-7α-methylestradiol
Routes of administration	By mouth^[1]
ATC code	L02BA (WHO)
Identifiers
IUPAC name (1S,9R,10S,11S,14R,15R)-14-(2-{4-(diethylamino)methyl-2-methoxyphenoxy}ethyl)-9,15-dimethyltetracyclo8.7.0.0^2,7.0^11,15heptadeca-2(7),3,5-trien-5-ol
CAS Number	229634-97-3 Citrate: 229634-98-4
PubChem CID	9874875 Citrate: 9874874
ChemSpider	8050564^Y Citrate: 8050563
UNII	42U0C8VOLO Citrate: 9B29N23K7E
CompTox Dashboard (EPA)	DTXSID601117925
Chemical and physical data
Formula	C₃₃H₄₇NO₃
Molar mass	505.743 g·mol⁻¹
3D model (JSmol)	Interactive image Citrate: Interactive image
SMILES CCN(CC)CC1=CC(=C(C=C1)OCCC@H2CCC@@H3C@@2(CCC@H4C@H3C@@H(CC5=C4C=CC(=C5)O)C)C)OC Citrate: CCN(CC)CC1=CC(=C(C=C1)OCCC@H2CCC@@H3C@@2(CCC@H4C@H3C@@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^Y Key:OHCPNHFLPCVWRG-MWSJHZLTSA-N^Y 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

Developmentedit

See alsoedit

Referencesedit

External linksedit