228266-34-0

Upstream product

• 1010-48-6 3-methyl-3-phenylbutanoic acid 
• 17016-83-0 (4S)-4-isopropyl-1,3-oxazolidin-2-one 
• 71-43-2 benzene 
• 3282-30-2 pivaloyl chloride 
• 96021-69-1 N-lithio-(4S)-4-isopropyl-2-oxazolidone 
• 541-47-9 3-Methylbutenoic acid 

Downstream Products

• 228266-35-1 (4S)-3-[(2S)-2-azido-3-methyl-3-phenylbutanoyl]-4-(propane-2-yl)-1,3-oxazolidine-2-one 
• 228266-37-3 methyl N-(tert-butoxycarbonyl)-β,β-dimethyl-L-phenylalanine ester 
• 228266-36-2 tert-butyl {(2S)-3-methyl-1-oxo-1-[(4S)-2-oxo-4-(propane-2-yl)-1,3-oxazolidine-3-yl]- 3-phenylbutane-2-yl}carbamate 
• 500229-32-3 N-(tert-butoxycarbonyl)-β,β-dimethyl-L-phenylalanine 
• 845292-32-2 Ethyl (E,4S)-4-[((2S)-2-{[(2S)-2,3-dimethyl-3-phenylbutanoyl]amino}-3,3-dimethylbutanoyl)(methyl)amino]-2,5-dimethyl-2-hexenoate 
• 765930-91-4 (2S)-2,3-dimethyl-3-phenylbutanoic acid 
• 765932-15-8 (4S)-3-[(2S)-2,3-dimethyl-3-phenylbutanoyl]-4-isopropyl-1,3-oxazolidin-2-one 

Relevant academic research and scientific papers

The antibody-drug conjugate hemiasterlin derivatives and their pharmaceutically (by machine translation)

[Problem] to give one specific target cell cytotoxic, normal cells to the cytotoxic is suppressed, the antibody-drug conjugate medicine hemiasterlin derivatives. (2) Formula [a]:[In the formula, mAb antibody expressed, q is 1 - 8 represents an integer of, h are 1 - 5 represents an integer of, g is an alanine residue (Ala) to represent, g is 1 - 4 represents an integer of, Y is a single bond or a formula (Y-a 1) is represented by the group, Z is formula (Z-a 1), equation (Z-a 2), equation (Z-a 3), formula (Z-a 4), formula (Z-a 5), type (Z-a 6), formula (Za-a 1), equation (Za-in 2), equation (Za-a 3), formula (Za-a 4), formula (Za-a 5), type (Za d 6), formula (Za-a 7), type (Za-in 8), or a group represented by formula (Za-a 10) (Za-a 9) formula a] is expressed by, antibody-drug conjugate or its pharmaceutically acceptable salt containing a drug. [Drawing] no (by machine translation)

MEDICINE CONTAINING ANTIBODY DRUG CONJUGATE CONTAINING HEMIASTERLIN DERIVATIVE

PROBLEM TO BE SOLVED: To provide medicines containing an antibody drug conjugate containing a hemiasterlin derivative, in which specific cytotoxicity to target cells is given, while cytotoxicity to normal cells is suppressed. SOLUTION: Provided is a medicine represented by formula (2-1), and containing an antibody drug conjugate or a pharmaceutically acceptable salt thereof [where, mAb represents an antibody, q represents an integer from 1 to 8, b represents an integer from 1 to 5, Z is a group represented by formula (Z-1), formula (Z-2), formula (Z-3), formula (Za-1), formula (Za-2), formula (Za-3), formula (Za-4), or formula (Za-5)]. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT

HEMIASTERLIN ANALOGS

This invention provides analogs of hemiasterlin, methods of synthesis of the analogs and use of the analogs as a cytotoxic anti-mitotic agents.

Conjugates of ligand linker and cytotoxic agent and related composition and methods of use

A conjugate comprising a ligand, a linker, and a cytotoxic agent, in which the linker is FALA, VLALA, ALAL, ALALA, ChaLALA, ChaChaLAL, NalChaLAL or NalLALA; a composition thereof; a method of delivering a cytotoxic agent in a cell-specific manner; and a method of treating cancer in a mammal.

Compounds for treating tumors

The invention provides compounds of formula (I): wherein E, A, B′, R6, R7, R8, and R9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.

Synthesis and biological activity of analogues of the antimicrotubule agent N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-carboxy-1- isopropylbut-2-enyl]-N13-dimethyl-L-valinamide (HTI-286)

Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent

Synthesis and antimitotic/cytotoxic activity of hemiasterlin analogues

The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.