ML-221

ML-221 is an antagonist of the G protein-coupled receptor (GPCR) APJ (IC50 = 4.8 µM). It is selective for APJ over the angiotensin II type 1 (AT1) receptor (IC50 = >78 µM). ML-221 antagonizes apelin 13-induced activation of APJ in cAMP and beta-arrestin recruitment assays (IC50s = 0.7 and 1.75 µM, respectively). It inhibits proliferation and angiogenesis in Mz-ChA-1 cholangiocarcinoma cells when used at concentrations ranging from 5 to 15 µM. In vivo, ML-221 (150 µg/kg) reduces tumor growth in a Mz-ChA-1 mouse xenograft model. Intrathecal injection of ML-221 (10 µg per animal) reduces mechanical allodynia and heat hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. ML-221 also inhibits pathological angiogenesis and enhances normal vessel recovery in retinal ischemic regions in a mouse model of oxygen-induced retinopathy.Formal Name: 5-[(4-nitrobenzoyl)oxy]-2-[(2-pyrimidinylthio)methyl]-4H-pyran-4-one. CAS Number: 877636-42-5. Molecular Formula: C17H11N3O6S. Formula Weight: 385.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMF:PBS (pH 7.2) (1:30): 0.03 mg/ml, DMSO: 1 mg/ml. lambdamax: 249 nm. SMILES: O=C1C(OC(C2=CC=C([N+]([O-])=O)C=C2)=O)=COC(CSC3=NC=CC=N3)=C1. InChi Code: InChI=1S/C17H11N3O6S/c21-14-8-13(10-27-17-18-6-1-7-19-17)25-9-15(14)26-16(22)11-2-4-12(5-3-11)20(23)24/h1-9H,10H2. InChi Key: UASIRTUMPRQVFY-UHFFFAOYSA-N.