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CFT1946 + trametinib
- Development stage
- Unknown
- Lead developer
- C4 Therapeutics, Inc.
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
CFT1946 + trametinib is an investigational **combination therapy** for solid tumors harboring BRAF V600 mutations. **CFT1946** is a novel, orally bioavailable BiDAC degrader that inhibits and degrades mutant BRAF V600 protein, avoiding paradoxical RAF activation and sparing wild-type BRAF V600[1]. **Trametinib** is a MEK1/MEK2 inhibitor approved as MEKINIST for BRAF-mutant melanoma and other BRAF V600-mutant cancers; it blocks MEK1 and MEK2 downstream of BRAF, reducing ERK pathway activation and cellular proliferation[3][4]. The combination aims to enhance antitumor effects and address resistance to existing BRAF inhibitors. It is being evaluated in phase 1/2 trials for multiple solid tumors, including melanoma, NSCLC, colorectal cancer, and anaplastic thyroid carcinoma in adults with BRAF V600-mutant cancers who have received prior therapies[1][3].
- Other names
- MEKINIST (trametinib)
02
Targets
MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)CRBN (Cereblon)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)CAPN3 (B-Raf proto-oncogene, serine/threonine kinase)
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