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BAY2666605
- Development stage
- Discontinued
- Lead developer
- Bayer
- Modality
- Molecular Glues → Targeted Protein Degraders (TPDs) → Small Molecules
- Administration
- Oral
01
Overview
BAY2666605 is an orally bioavailable small molecule and first-in-class "velcrin" that acts as a molecular glue to induce the formation of a complex between phosphodiesterase 3A (PDE3A) and Schlafen family member 12 (SLFN12). This complex formation activates the RNase activity of SLFN12, leading to cleavage of tRNA–Leu–TAA, global inhibition of protein synthesis, and apoptosis in cancer cells that coexpress both proteins. The antineoplastic effect is independent of PDE3A enzymatic inhibition. Developed by Bayer for advanced solid tumors—including metastatic melanoma, glioblastoma, ovarian cancer, sarcomas—BAY2666605 showed preclinical efficacy but was discontinued in clinical development due to dose-limiting thrombocytopenia related to on-target effects in platelets[1][2][3][4][5][8].
- Other names
- 2275774-60-0XC4ZA6OSY6XC-4ZA6OSY6XC 4ZA6OSY6UNII-XC4ZA6OSY6UNII-XC-4ZA6OSY6UNII-XC 4ZA6OSY6
02
Targets
SLFN12 (Schlafen family member 12)
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