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Details

Stereochemistry EPIMERIC
Molecular Formula C46H63NO15
Molecular Weight 869.9901
Optical Activity UNSPECIFIED
Defined Stereocenters 12 / 13
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TPI-287

SMILES

[H][C@@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]4(O)C[C@H](OC(=O)[C@H](O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)C(C)=C([C@H](OC(C)=O)[C@@H]5OC(O[C@@H](C[C@H]6OC[C@@]16OC(C)=O)[C@]25C)C=C)C4(C)C

InChI

InChIKey=FDTAUJJRHBRHIJ-FDJAAIFISA-N
InChI=1S/C46H63NO15/c1-13-32-58-30-20-31-45(22-55-31,61-26(6)49)36-38(60-39(51)27-17-15-14-16-18-27)46(54)21-29(57-40(52)34(50)28(19-23(2)3)47-41(53)62-42(7,8)9)24(4)33(43(46,10)11)35(56-25(5)48)37(59-32)44(30,36)12/h13-18,23,28-32,34-38,50,54H,1,19-22H2,2-12H3,(H,47,53)/t28-,29-,30-,31+,32?,34+,35-,36-,37-,38-,44+,45-,46+/m0/s1

HIDE SMILES / InChI

Description

TPI-287 is a microtubule stabilizer. TPI-287 readily crossed the normal BBB. While paclitaxel and TPI-287 showed similar cytotoxicity to breast cancer cells in vitro, and in a model of primary breast tumors, only TPI-287 was able to significantly reduce metastatic colonization of breast cancer in the brain. TPI-287 is a poor substrate for the P-gp efflux pump. Potential limitation to the clinical use of TPI-287 is the weight loss observed upon treatment. This loss recovered after cessation of treatment in the early treatment model, and may be ameliorated by hydration. TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma. The combination of TPI 287 and temozolomide is well tolerated in patients with metastatic melanoma, with the exception of neuropathy. TPI 287 is in phase II clinical trial for the treatment of breast cancer, glioblastoma and malignant melanoma.

CNS Activity

Originator

Approval Year

PubMed

Patents