DDO-4033 is a potent SPOP inhibitor through virtual screening and optimization. DDO-4033 exhibited potent affinity with SPOP in vitro and efficiently impeded the malignant migration, invasion, and proliferation of ccRCC cell lines. DDO-4033 disrupted the SPOP recruitment of substrate LATS1 and inhibited the polyubiquitination and subsequent degradation, resulting in the upregulation of tumor suppressor LATS1. The increased abundance of LATS1 inactivated the transcriptional factors YAP1 and WWTR1/TAZ, ultimately turning on the Hippo signaling pathway in kidney cancer cells.
MedKoo Cat#: 129100
Name: DDO-4033
CAS#: N/A
Chemical Formula: C20H24N6O4
Exact Mass: 412.1859
Molecular Weight: 412.45
Elemental Analysis: C, 58.24; H, 5.87; N, 20.38; O, 15.52
The following data is based on the product molecular weight 412.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Zhang Q, Zhou Y, Zhao J, Hu L, Zhu Z, Wang H, Jin Y, You Q, Jiang Z, Guo X. Discovery of 2-Pyrazolylpyrimidinone Derivatives as New SPOP Inhibitors for Renal Cell Carcinoma Therapy. J Med Chem. 2025 Jul 7. doi: 10.1021/acs.jmedchem.5c00987. Epub ahead of print. PMID: 40622869.
