API-1

API-1 is an inhibitor of Akt that reduces the level of phosphorylated Akt (IC50 = ~0.8 µM in OVCAR3 cells) by binding to Akt and blocking its translocation to the cell membrane. It reduces cell proliferation in various cancer cell lines, induces apoptosis, and, at a dose of 10 mg/kg per day, decreases tumor growth in a mouse xenograft model. API-1 inhibition of Akt leads to proteasomal degradation of the downstream mediator Mcl-1. Likely independent of Akt binding, API-1 inhibits cell growth (IC50s = 2-5 µM) and induces apoptosis in non-small cell lung and head and neck squamous cancer (NSCLC and HNSCC) cell lines with concomitant increases in caspase-3, -8, and -9 cleavage. It reduces the levels of cellular FLICE-inhibitory protein (c-FLIP), an important regulator of apoptosis, through ubiquitin- and proteasome-mediated degradation. It also has a synergistic effect on apoptosis in combination with TRAIL/APO-2L. The information regarding the reduction in phosphorylated Akt levels, IC50 value, translocation, cell proliferation, and xenograft tumor growth was drawn from a paper that has been retracted, however, the information specified in the retraction statement has not been included.Formal Name: 4-amino-5,8-dihydro-5-oxo-8-beta-D-ribofuranosyl-pyrido[2,3-d]pyrimidine-6-carboxamide. CAS Number: 36707-00-3. Synonyms: NSC 177223. Molecular Formula: C13H15N5O6. Formula Weight: 337.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: slightly soluble, DMSO: 2 mg/ml. lambdamax: 275, 302 nm. SMILES: O=C1C2=C(N)N=CN=C2N([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)C=C1C(N)=O. InChi Code: InChI=1S/C13H15N5O6/c14-10-6-7(20)4(11(15)23)1-18(12(6)17-3-16-10)13-9(22)8(21)5(2-19)24-13/h1,3,5,8-9,13,19,21-22H,2H2,(H2,15,23)(H2,14,16,17)/t5-,8-,9-,13-/m1/s1. InChi Key: SPBWHPXCWJLQRU-FITJORAGSA-N.