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PF-07248144 + vepdegestrant
- Development stage
- Unknown
- Lead developer
- Pfizer
- 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
PF-07248144 + vepdegestrant is an investigational **combination therapy** under clinical development for the treatment of advanced or metastatic solid tumors, particularly estrogen receptor-positive, HER2-negative metastatic breast cancer. **PF-07248144** is a small molecule inhibitor of **lysine acetyltransferases KAT6A and KAT6B**, which alters oncogenic chromatin activity and transcription. **Vepdegestrant** (ARV-471) is a selective estrogen receptor degrader (SERD) and a proteolysis-targeting chimera (PROTAC) that targets the estrogen receptor for degradation, thus blocking estrogen signaling. The combination aims to provide synergistic antitumor effects by simultaneously targeting **epigenetic regulation** (via KAT6 inhibition) and **estrogen receptor signaling**. Preliminary clinical results suggest a tolerable safety profile and evidence of antitumor activity, and both drugs are currently in a phase 1 trial in combination[1][3][4][5].
- Other names
- ARV-471ARV471ARV 471
02
Targets
KAT6A (Lysine acetyltransferase 6A)ESR1 (ERα)KAT6B (Histone acetyltransferase KAT6B)
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