C-02

C-02 is a proteolysis-targeting chimera (PROTAC) composed of the hexokinase inhibitor lonidamine (Cay-14640) linked to the cereblon ligand thalidomide (Cay-14610). It induces degradation of hexokinase 2 in 786-O and PANC-1 cells when used at a concentration of 20 µM. C-02 is cytotoxic to 786-O, 4T1, PANC-1, HGC-27, and MCF-7 cancer cells (IC50s = 34.07, 5.08, 31.53, 6.11, and 21.65 µM, respectively). It reduces the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in 4T1 cells, indicating inhibition of glycolysis and mitochondrial damage, respectively, when used at a concentration of 20 µM. In vivo, C-02 (50 mg/kg) reduces tumor volume and induces intratumoral cytokine accumulation and pyroptosis in a 4T1 murine mammary carcinoma model.Formal Name: 1-(2,4-dichlorobenzyl)-N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-1H-indazole-3-carboxamide. Molecular Formula: C32H28Cl2N6O5. Formula Weight: 647.5. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: Ethanol: Soluble, Methanol: Soluble. SMILES: O=C(N(C1C(NC(CC1)=O)=O)C2=O)C3=C2C=CC=C3NCCCCNC(C4=NN(CC5=C(Cl)C=C(Cl)C=C5)C6=C4C=CC=C6)=O. InChi Code: InChI=1S/C32H28Cl2N6O5/c33-19-11-10-18(22(34)16-19)17-39-24-9-2-1-6-20(24)28(38-39)30(43)36-15-4-3-14-35-23-8-5-7-21-27(23)32(45)40(31(21)44)25-12-13-26(41)37-29(25)42/h1-2,5-11,16,25,35H,3-4,12-15,17H2,(H,36,43)(H,37,41,42). InChi Key: OFEUWOIETWIJID-UHFFFAOYSA-N.