CAY10585

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of a HIF-1alpha subunit and HIF-1beta subunit. Whereas the HIF-1beta subunit is constitutively expressed, the HIF-1alpha subunit is regulated by cellular oxygen levels and therefore plays an important role in maintaining cellular oxygen homeostasis. Under normoxic conditions, HIF-1alpha is selectively hydroxylated on proline residues 402 and 577 and targeted for destruction by the ubiquitin-proteasome system. Under hypoxic conditions, HIF-1alpha accumulates and dimerizes with HIF-1beta to promote the transcription of a number of genes involved in angiogenesis, glycolysis, growth factor signaling, tumor invasion, and metastasis. CAY10585 is a novel small molecule inhibitor of HIF-1alpha accumulation and gene transcriptional activity. In a gene reporter assay using human Hep3B and AGS cell lines, CAY10585 prevented HIF-1 transcriptional activity with IC50 values of 2.6 and 0.7 µM, respectively. It blocks HIF-1alpha accumulation in Hep3B cells in a concentration and time-dependent manner, with complete inhibition at a concentration of 30 µM within 12 hours. CAY10585 also significantly suppresses transcription of the HIF-1 target genes VEGF and erythropoietin at 10 µM.Formal Name: 4-hydroxy-3-[[2-(4-tricyclo[3.3.1.13,7]dec-1-ylphenoxy)acetyl]amino]-benzoic acid, methyl ester. CAS Number: 934593-90-5. Synonyms: Hypoxia-Inducible Factor-1alpha Inhibitor. Molecular Formula: C26H29NO5. Formula Weight: 435.5. Purity: >97%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 10 mg/ml. lambdamax: 234, 260 nm. SMILES: O=C(NC1=CC(C(OC)=O)=CC=C1O)COC2=CC=C(C3(C[C@@H](C4)C5)C[C@H]5CC4C3)C=C2. InChi Code: InChI=1S/C26H29NO5/c1-31-25(30)19-2-7-23(28)22(11-19)27-24(29)15-32-21-5-3-20(4-6-21)26-12-16-8-17(13-26)10-18(9-16)14-26/h2-7,11,16-18,28H,8-10,12-15H2,1H3,(H,27,29)/t16-,17-,18?,26?/m1/s1. InChi Key: BJRPPNOJYFZSLY-DVYMTOFQSA-N.