Delving into the Latest Updates on BAM7 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

BAX

Mechanism

BAX agonists(Apoptosis regulator BAX agonists)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Dana-Farber Cancer Institute, Inc.

Active Organization

Dana-Farber Cancer Institute, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC21H19N5O2S

InChIKeyKOCVKGYKBLJEPK-UHFFFAOYSA-N

CAS Registry331244-89-4

Author: Pietrobono, Deborah ; La Regina, Giuseppe ; Trincavelli, Maria Letizia ; Costa, Barbara ; Daniele, Simona ; Taliani, Sabrina ; Silvestri, Romano ; Giacomelli, Chiara ; Novellino, Ettore ; Giustiniano, Mariateresa ; Marinelli, Luciana ; Martini, Claudia ; Da Settimo, Federico ; La Pietra, Valeria

Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inhibition of pro-apoptotic ones, which help to escape apoptosis. Among pro-apoptotic inducers, the Bcl-2 family protein Bax has recently emerged as a promising new target in cancer therapy along with first BAX activators (BAM7, Compound 106, and SMBA1). Herein, a derivative of BAM-7, named BTC-8, was employed to explore the effects of Bax activation in different human GBM cells and in their stem cell subpopulation. BTC-8 inhibited GBM cell proliferation, arrested the cell cycle, and induced apoptosis through the induction of mitochondrial membrane permeabilization. Most importantly, BTC-8 blocked proliferation and self-renewal of GSCs and induced their apoptosis. Notably, BTC-8 was demonstrated to sensitize both GBM cells and GSCs to the alkylating agent Temozolomide. Overall, our findings shed light on the effects and the relative molecular mechanisms related to Bax activation in GBM, and they suggest Bax-targeting compounds as promising therapeutic tools against the GSC reservoir.

100 Deals associated with BAM7

Login to view more data