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cobimetinib + pictilisib
- Development stage
- Discontinued
- Lead developer
- Genentech
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Cobimetinib + pictilisib is an experimental **combination therapy** of two targeted small molecule inhibitors: **cobimetinib**, a reversible inhibitor of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2), and **pictilisib**, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor. The combination was investigated primarily for potential synergy in treating patients with advanced solid tumors, including BRAF-mutant melanoma and KRAS-mutant endometrioid adenocarcinoma. The rationale is dual blockade of the MAPK and PI3K pathways, often co-activated or compensating in tumor resistance, to induce apoptosis and maximize antitumor activity. Clinical trials found limited tolerability and modest efficacy, with the development of combined resistance observed in preclinical models[1][3][5].
- Other names
- cobimetinib and pictilisib combinationMEK inhibitor and pan-PI3K inhibitor combination
02
Targets
MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)PI3K (Phosphoinositide-3-kinase regulatory subunit 6)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)mTOR (Mammalian target of rapamycin kinase)
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