AMSILAROTENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H27NO3Si2
Molecular Weight	385.6043
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[Si](C)(C)C1=CC(=CC(=C1)C(=O)NC2=CC=C(C=C2)C(O)=O)[Si](C)(C)C

InChI

InChIKey=VVTNSTLJOVCBDL-UHFFFAOYSA-N

InChI=1S/C20H27NO3Si2/c1-25(2,3)17-11-15(12-18(13-17)26(4,5)6)19(22)21-16-9-7-14(8-10-16)20(23)24/h7-13H,1-6H3,(H,21,22)(H,23,24)

HIDE SMILES / InChI

Molecular Formula	C20H27NO3Si2
Molecular Weight	385.6043
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://adisinsight.springer.com/drugs/800010773 | https://www.ncbi.nlm.nih.gov/pubmed/22587457 | https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C38684

Amsilarotene (TAC-101) is a retinobenzoic acid (RAR) derivative with high affinity to the RAR-alpha receptor. It is a Retinoic acid receptor alpha antagonist. Amsilarotene is an orally absorbed synthetic retinoid. This analogue of vitamin A (retinol) binds to nuclear retinoic acid receptor-a (RAR-a), activates RAR-a transcriptional activity, and has shown antitumor activity in primary and metastatic preclinical models of liver cancer. Amsilarotene inhibits retinoblastoma-gene product (RB) phosphorylation and increases the presence of 2 cyclin-dependent kinase (CDK) inhibitors, resulting in cell cycle arrest. This agent also causes a cytotoxic decline in cyclin A and thymidylate synthase expression.Amsilarotene inhibits tumor growth in the liver with low toxicity and markedly improves survival in both primary HCC and metastatic colon cancer models. It was in phase II clinical development with Taiho Pharmaceutical for liver cancer, however it was discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
TAC-101 inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma.	2003 Aug 20	12957355
A novel retinoid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), induces apoptosis of human ovarian carcinoma cells and shows potential as a new antitumor agent for clear cell adenocarcinoma.	2004 Sep	15350353
4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induces apoptosis in colon cancer partially through the induction of Fas expression.	2005 Jan-Feb	15796164
Gateways to clinical trials.	2009 Apr	19536362

Patents

Sample Use Guides

In Vivo Use Guide

In a phase I/II study, TAC-101 was administered orally in 21-day cycles (14 days on/7 days off) to patients with advanced HCC. In the phase I portion of the study, the initial dose was 40 mg/day. Two patients had DLT, and the dose was reduced to 20 mg/day. Since only 1 of 6 assessable patients had DLT during the first two cycles of therapy, 20 mg/day was designated as the maximum tolerated dose (MTD) for the 21-day treatment cycle. At this dose level, TAC-101 was generally well tolerated

Route of Administration: Oral

In Vitro Use Guide

In vitro, TAC-101 at the concentration of more than 10 uM showed direct cytotoxicity against JHH-7 cells caused by induction of apoptosis.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:20:17 UTC 2023` Edited by `admin` on `Sat Dec 16 16:20:17 UTC 2023`
Record UNII	Q1418F39MH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMSILAROTENE

Official Name

English

Am555S

Code

English

amsilarotene [INN]

Common Name

English

TAC-101

Code

English

Amsilarotene [WHO-DD]

Common Name

English

Am-555S

Code

English

TAC101

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C804