Gambogic Acid

Gambogic acid (GA) is a xanthonoid that has been found in G. hanburyi resin and has anticancer activity. It binds covalently to the regulatory subunit B (SPTSSB) of the serine palmitoyltransferase complex (Ki = 1.5 µM, kinact = 0.05 min-1) and inhibits de novo sphingolipid biosynthesis. GA activates caspases in T47D breast cancer cells (EC50 = 0.78 µM) and inhibits binding of anti-apoptotic proteins to a BH3 peptide (IC50s = 1.47, 1.21, 2.02, 0.66, 1.06, and 0.79 µM for Bcl-xL, Bcl-2, Bcl-W, Bcl-B, Bfl-1, and Mcl-1, respectively), as well as decreases the expression of Bcl-2 and increases the expression of Bax in MGC-803 human gastric carcinoma cells. GA binds to the transferrin receptor (IC50 = 4.1 µM), reduces growth of a variety of cancer cell lines (GI50s = 0.115-1 µM), and induces apoptosis in T47D cells. It also inhibits growth of U87 glioma cells, as well as increases the levels of leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1), decreases the levels of EGFR, and reduces Akt/mTORC1 signaling in these cells. GA inhibits the chymotrypsin activity of the 20S proteasome in a dose-dependent manner and is a slow inhibitor of inward-rectifying potassium channel 2.1 (Kir2.1, IC50 = <0.1 µM).Formal Name: 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-buten-1-yl)-11-(4-methyl-3-penten-1-yl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3,4-g]pyrano[3,2-b]xanthen-1-yl]-2Z-butenoic acid. CAS Number: 2752-65-0. Synonyms: GA, beta-Guttiferin. Molecular Formula: C38H44O8. Formula Weight: 628.8. Purity: >95% (mixture of epimers). Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 16.7 mg/ml, DMSO: 16.7 mg/ml, Ethanol: 25 mg/ml, Ethanol:PBS (pH 7.2) (1:3): 0.25 mg/ml. lambdamax: 291, 361 nm. SMILES: C/C(C(O)=O)=C/C[C@@]1(OC(C)(C)[C@]2([H])C3)[C@@]2(OC4=C(C5=C6C=C[C@](CC/C=C(C)/C)(C)O5)C/C=C(C)/C)C(C(C4=C6O)=O)=C[C@@]3([H])C1=O. InChi Code: InChI=1S/C38H44O8/c1-20(2)10-9-15-36(8)16-14-24-29(39)28-30(40)26-18-23-19-27-35(6,7)46-37(33(23)41,17-13-22(5)34(42)43)38(26,27)45-32(28)25(31(24)44-36)12-11-21(3)4/h10-11,13-14,16,18,23,27,39H,9,12,15,17,19H2,1-8H3,(H,42,43)/b22-13-/t23-,27+,36-,37. InChi Key: GEZHEQNLKAOMCA-RRZNCOCZSA-N.