SIMOTAXEL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C46H57NO15S
Molecular Weight	896.007
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)OC(=O)N[C@H]([C@@H](O)C(=O)O[C@H]1C[C@@]2(O)[C@@H](OC(=O)C3=CC=CC=C3)[C@@H]4[C@@]5(CO[C@@H]5C[C@H](O)[C@@]4(C)C(=O)[C@H](OC(=O)C6CCCC6)C(=C1C)C2(C)C)OC(C)=O)C7=CC=CS7

InChI

InChIKey=SLGIWUWTSWJBQE-VLCCYYTCSA-N

InChI=1S/C46H57NO15S/c1-23(2)58-42(55)47-33(29-18-13-19-63-29)34(50)41(54)59-28-21-46(56)38(61-40(53)27-14-9-8-10-15-27)36-44(7,30(49)20-31-45(36,22-57-31)62-25(4)48)37(51)35(32(24(28)3)43(46,5)6)60-39(52)26-16-11-12-17-26/h8-10,13-15,18-19,23,26,28,30-31,33-36,38,49-50,56H,11-12,16-17,20-22H2,1-7H3,(H,47,55)/t28-,30-,31+,33-,34+,35+,36-,38-,44+,45-,46+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800021158 | https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C116871 | https://www.ncbi.nlm.nih.gov/pubmed/16740771

Simotaxel (MST-997) is a semi-synthetic, orally bioavailable, third-generation taxane derivative and microtubule-stabilizing agent, with potential antineoplastic activity. Simotaxel was being developed through a collaboration between Wyeth (later Pfizer) and Taxolog as a potential treatment for cancer. Upon administration, simotaxel binds to tubulin, promotes microtubule assembly and stabilization, and prevents microtubule depolymerization. This results in G2/M arrest, apoptosis and the inhibition of cell proliferation in susceptible tumor cells. This agent is a poor substrate for P-glycoprotein-related drug resistance mechanisms; therefore, it may be useful for treating multi-drug resistant tumors. MST-997 is more potent than paclitaxel and docetaxel and overcomes paclitaxel and docetaxel resistance in certain tumor cell types. Simotaxel is under investigation in clinical trial NCT00088647 (study evaluating MST-997 in advanced malignant solid tumors).

Originator

Approval Year

PubMed

Title	Date	PubMed
Preclinical pharmacologic evaluation of MST-997, an orally active taxane with superior in vitro and in vivo efficacy in paclitaxel- and docetaxel-resistant tumor models.	2006-06-01	16740771

Patents

Sample Use Guides

In Vivo Use Guide

Nude mice bearing small-established Lox melanoma xenografts were treated with 10 to 120 mg/kg Simotaxel (MST-997) given as a single i.v. dose in Intralipid on day 1 (defined henceforth as the day after tumor weight off 100 mg was achieved). A clear dose response was observed with a maximum efficacious dose of 100 mg/kg and the minimum efficacious dose of 10 mg/kg. No tumors were detected in 9 of 10animals receiving the 100 and 70 mg/kg doses up to 56 days after drug administration and as such were defined as cured. The MTD was 120 mg/kg.

Route of Administration: Intravenous

In Vitro Use Guide

Simotaxel (MST-997) induced microtubule polymerization (EC50 = 0.9 umol/L) and bundling, resulting in G2-M arrest and apoptosis. In addition, MST-997 was a potent inhibitor of paclitaxel- and docetaxel-sensitive tumor cell lines that did not have detectable P-glycoprotein (IC50 = 1.8 +/- 1.5 nmol/L). 0.3 to 30 nmol/L MST-997 caused an accumulation of phosphorylated nucleolin, a selective marker for cells arrested in G2-M in intact KB-3-1 cells in vitro.

Name

Type

Language

SIMOTAXEL

Official Name

English

MST-997

Preferred Name

English

SIMOTAXEL [USAN]

Common Name

English

simotaxel [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1490