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Drug intelligence / Profile preview
CREB1-PROTAC compound #28
- Development stage
- Preclinical
- Lead developer
- The Ohio State University
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
01
Overview
CREB1-PROTAC compound #28 is a proteolysis-targeting chimera (PROTAC) designed to target and degrade cAMP-responsive element-binding protein 1 (CREB1) via the ubiquitin-proteasome system. Developed by the Medicinal Chemistry Core at the Ohio State University, the compound is built on the backbone of the CREB1 inhibitor 666-15. In preclinical models of multiple myeloma, compound #28 demonstrated potent degradation of CREB1, leading to reduced cell viability, induction of apoptosis, and downregulation of downstream targets such as TXNIP, HLA-E, MCL1, and BCL2. It has also shown synergistic effects when combined with immunomodulatory drugs like lenalidomide, pomalidomide, and iberdomide.
02
Targets
26S proteasomeCREB1 (cAMP response element-binding protein 1)CRL4-CRBN (Cereblon-based E3 ubiquitin ligase complex)
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