Product Name: Pyridoclax
 CAT#: A-1382

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 Synonym: Pyridoclax,MR-29072

Pyridoclax Chemical Structure
Pyridoclax chemical structure

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Biological Activity
Pyridoclax(MR-29072) is a potent Mcl-1 inhibitor with Kd value of 25 nM.
Target: Mcl1 inhibitor
Pyridoclax is able to disrupt BimL/Mcl-1 interaction in whole living cells. Pyridoclax strongly sensitizes ovarian cancer chemoresistant IGROV1-R10 cells to Bcl-xL targeting siRNA, their combination leading to massive apoptosis. Neither ABT-737 nor Pyridoclax induced cell death as single agents, whereas their combination led to massive apoptotic cell death in both IGROV1-R10 and SKOV3 chemoresistant ovarian cancer cell lines.
Technical Data

Solubility:Soluble in DMSO
Purity: >99%
Storage Conditions: Room temperature, or -20ºC for 3 years.

Apoptosis control defect such as the deregulation of Bcl-2 family members expression is frequently involved in chemoresistance. In ovarian carcinoma, we previously demonstrated that Bcl-xL and Mcl-1 cooperate to protect cancer cells against apoptosis and their concomitant inhibition leads to massive apoptosis even in absence of chemotherapy. Whereas Bcl-xL inhibitors are now available Mcl-1 inhibition, required to sensitize cells to Bcl-xL-targeting strategies, remains problematic. In this context, we designed and synthesized oligopyridines potentially targeting Mcl-1 hydrophobic pocket, evaluated their capacity to inhibit Mcl-1 in live cells and implemented functional screening assay to evaluate their ability to sensitize ovarian carcinoma cells to Bcl-xL-targeting strategies. We established structure-activity relationships and focused our attention on MR29072, named Pyridoclax. Surface plasmon resonance assay demonstrated that Pyridoclax directly binds to Mcl-1. Without cytotoxic activity as single agent, Pyridoclax induced apoptosis in combination with Bcl xL-targeting siRNA or with ABT-737 in ovarian, lung and mesothelioma cancer cells.

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