TPI-287

Investigational

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 Search

SMILES

CC(C)C[C@H](NC(=O)OC(C)(C)C)[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]6OC(O[C@@H]([C@@H](OC(C)=O)C(=C1C)C2(C)C)[C@@]46C)C=C)OC(C)=O

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

Molecular Formula	C46H63NO15
Molecular Weight	869.9901
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	12 / 13
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26235333 | https://www.ncbi.nlm.nih.gov/pubmed/27540836 | https://www.ncbi.nlm.nih.gov/pubmed/22622283 | https://adisinsight.springer.com/drugs/800019429

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

Title	Date	PubMed
The CNS penetrating taxane TPI 287 and the AURKA inhibitor alisertib induce synergistic apoptosis in glioblastoma cells.	2018-05	29396807
Crafting of Neuroprotective Octapeptide from Taxol-Binding Pocket of β-Tubulin.	2018-03-21	29155559
Current challenges in the management of breast cancer brain metastases.	2017-04	28923217
A phase I study of TPI 287 in combination with temozolomide for patients with metastatic melanoma.	2016-12	27540836
A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma.	2016-01	26235333
TPI-287, a new taxane family member, reduces the brain metastatic colonization of breast cancer cells.	2012-09	22622283

Patents

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:10:52 GMT 2025` Edited by `admin` on `Mon Mar 31 18:10:52 GMT 2025`
Record UNII	A2VM2V569A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TPI-287

Preferred Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

335611