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
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)
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 |
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A potential use of a synthetic retinoid TAC-101 as an orally active agent that blocks angiogenesis in liver metastases of human stomach cancer cells. | 2001 Nov |
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Anti-tumor effect of vitamin A and D on head and neck squamous cell carcinoma. | 2003 Dec |
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Effect of synthetic retinoid, TAC-101, on experimental autoimmune disease. | 2003 Jan |
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4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid inhibits angiogenesis in colon cancer through reduced expression of vascular endothelial growth factor. | 2004 |
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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 |
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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 |
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4- [3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induced fas expression and activated caspase-3 and -8 in a DLD-1 colon cancer cell line. | 2007 Mar-Apr |
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Contribution of AP-1 interference induced by TAC-101 to tumor growth suppression in a hepatocellular carcinoma model. | 2009 |
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Retinoic acid receptor stimulation protects midbrain dopaminergic neurons from inflammatory degeneration via BDNF-mediated signaling. | 2009 Jul |
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Chemopreventive effect of 4-[3,5-Bis(trimethylsilyl) benzamido] benzoic acid (TAC-101) on MNU-induced colon carcinogenesis in a rat model. | 2009 Jun |
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Using a water-immiscible ionic liquid to improve asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one catalyzed by immobilized Candida parapsilosis CCTCC M203011 cells. | 2009 Oct 22 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22587457
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9932610
In vitro, TAC-101 at the concentration of more than 10 uM showed direct cytotoxicity against JHH-7 cells caused by induction of apoptosis.
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NCI_THESAURUS |
C804
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EU-Orphan Drug |
EU/3/07/497
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C38684
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ACTIVE MOIETY