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The hypoxia-inducible factor (HIF) transcription factors are members of the basic-helix-loop-helix (bHLH) family of transcription factors and play important roles in maintaining cellular oxygen homeostasis. HIF-1alpha has emerged as an important drug target in breast and prostate cancer, cardiovascular disease, and ischemia. ML-228 is an activator of the HIF signaling pathway, as demonstrated by HIF response element (HRE) reporter assay (EC50 = 1.2 µM), HIF-1alpha nuclear translocation assay (EC50 = 1.3 µM), and increased VEGF expression (EC50 = 1.6 µM). Its activity in the HRE assay is blocked by excess iron, suggesting that ML-228 can chelate iron. Molecular modeling indicates that ML-228 does not modulate HIF signaling by binding to prolyl hydroxyases. ML-228 also significantly inhibits ligand binding to several channels, receptors, and transporters, including ERG potassium channel, 5-HT2B and A3 adenosine receptors, and dopamine transporter.Formal Name: N-([1,1'-biphenyl]-4-ylmethyl)-6-phenyl-3-(2-pyridinyl)-1,2,4-triazin-5-amine. CAS Number: 1357171-62-0. Synonyms: CID-46742353. Molecular Formula: C27H21N5. Formula Weight: 415.5. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 25 mg/ml, Ethanol: 30 mg/ml, Ethanol:PBS (pH 7.2)(1:2): 0.25 mg/ml. lambdamax: 268, 328 nm. SMILES: C1(C2=NC(NCC3=CC=C(C4=CC=CC=C4)C=C3)=C(C5=CC=CC=C5)N=N2)=NC=CC=C1. InChi Code: InChI=1S/C27H21N5/c1-3-9-21(10-4-1)22-16-14-20(15-17-22)19-29-27-25(23-11-5-2-6-12-23)31-32-26(30-27)24-13-7-8-18-28-24/h1-18H,19H2,(H,29,30,32). InChi Key: QNRODODTMXCRKU-UHFFFAOYSA-N.
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