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binimetinib + hydroxychloroquine

Development stage: Unknown
Lead developer: Pfizer
Modality: Small Molecules
Administration: Oral

Overview

A combination therapy consisting of binimetinib, a MEK 1/2 inhibitor, and hydroxychloroquine, an autophagy inhibitor. This combination was developed based on preclinical evidence suggesting synthetic lethality in RAS-mutant tumors when MEK inhibition is combined with autophagy blockade. The scientific rationale is that KRAS mutations activate the MAPK signaling cascade, and while MEK inhibition alone often leads to resistance mechanisms including upregulation of autophagy, blocking autophagy with hydroxychloroquine may overcome this resistance.

Targets

MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)

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