Compound: cortistatin A
SMILES: O1[C@@]23C(C=C4[C@]1(C[C@H](N(C)C)[C@H]([C@@H]4O)O)CC2)=CC[C@]5([C@H]3CC[C@@H]5c6cc7c(ccnc7)cc6)C
InChIKey: KSGZCKSNTAJOJS-DZBMUNJRSA-N
Synonyms: cortistatin A, (+)-cortistatin A, Cortistatine A, 882976-95-6, 6VG04XOV89, CHEBI:67171, DTXSID10468617, (1R,2R,3S,5R)-3-(dimethylamino)-17beta-(isoquinolin-7-yl)-5,8alpha-epoxy-9,19-cyclo-9,10-secoandrosta-9(11),10-diene-1,2-diol, (3S,3aR,7R,8R,9S,10aR,12aS,12bR)-9-(Dimethylamino)-1,2,3,3a,4,7,8,9,10,11,12,12b-dodecahydro-3-(7-isoquinolinyl)-3a-methyl-10a,12a-epoxybenzo(4,5)cyclohept(1,2-E)indene-7,8-diol, 10a,12a-Epoxybenzo(4,5)cyclohept(1,2-E)indene-7,8-diol, 9-(dimethylamino)-1,2,3,3a,4,7,8,9,10,11,12,12b-dodecahydro-3-(7-isoquinolinyl)-3a-methyl-, (3S,3aR,7R,8R,9S,10aR,12aS,12bR)-, (1S,2R,5S,6R,12R,13R,14S,16R)-14-(dimethylamino)-5-isoquinolin-7-yl-6-methyl-19-oxapentacyclo[14.2.1.01,9.02,6.011,16]nonadeca-8,10-diene-12,13-diol, 10a,12a-Epoxybenzo[4,5]cyclohept[1,2-e]indene-7,8-diol, 9-(dimethylamino)-1,2,3,3a,4,7,8,9,10,11,12,12b-dodecahydro-3-(7-isoquinolinyl)-3a-methyl-, (3S,3aR,7R,8R,9S,10aR,12aS,12bR)-, (1S,2R,5S,6R,12R,13R,14S,16R)-14-(dimethylamino)-5-isoquinolin-7-yl-6-methyl-19-oxapentacyclo(14.2.1.01,9.02,6.011,16)nonadeca-8,10-diene-12,13-diol, RefChem:906061, DTXCID00419436, Cortistatin A [MI], 17-epi-Cortistatin A, CHEMBL4080906, Cortistatin-A, (1R,2R,3S,5R,8alpha,17beta)-3-(dimethylamino)-17-(isoquinolin-7-yl)-5,8-epoxy-9,19-cyclo-9,10-secoandrosta-9(11),10-diene-1,2-diol, (3S,3aR,7R,8R,9S,10aR,12aS,12bR)-9-(Dimethylamino)-3-(isoquinolin-7-yl)-3a-methyl-1,2,3,3a,4,7,8,9,10,11,12,12b-dodecahydro-10a,12a-epoxybenzo[4,5]cyclohepta[1,2-e]indene-7,8-diol, UNII-6VG04XOV89, GTPL9885, orb1703583, SCHEMBL12431713, SCHEMBL31343248, BDBM50248631, AKOS040745681, Q5173335, (1R,2R,3S,5R)-3-(Dimethylamino)-17beta-(isoquinolin-7-yl)-5,8-epoxy-9,19-cyclo-9,10-secoandrosta-9(11),10-diene-1,2-diol, (1R,2R,3S,5R,17alpha)-3-(dimethylamino)-17-(isoquinolin-7-yl)-5,8-epoxy-9,19-cyclo-9,10-secoandrosta-9(11),10-diene-1,2-diol, C1I
Theoretical properties:
molecular_formula: C30H36N2O3
molecular_weight: 472.6 g/mol
exact_mass: 472.27259301 g/mol
formal_charge: 0
hydrogen_bond_donor_count: 2
hydrogen_bond_acceptor_count: 5
rotatable_bond_count: 2
heavy_atom_count: 35
topological_polar_surface_area: 65.8 Å²
isotope_atom_count: 0
covalently_bonded_unit_count: 1
Physical properties:
Descriptions:
{"pubchem": "Cortistatin A is a member of the class of cortistatins that is substituted by hydroxy groups at positions 1 and 2, a dimethylamino group at the 3alpha position and an isoquinolin-7-yl group at the 17 position, with double bonds at the 9-11 and 10-19 positions (the 1R,2R,17beta enantiomer). It is a diol, a secondary alcohol and a member of cortistatins.", "chebi": "A member of the class of cortistatins that is substituted by hydroxy groups at positions 1 and 2, a dimethylamino group at the 3\u03b1 position and an isoquinolin-7-yl group at the 17 position, with double bonds at the 9-11 and 10-19 positions (the 1<i>R</i>,2<i>R</i>,17\u03b2 enantiomer).", "chembl": null, "wikipedia": "The cortistatins are a group of steroidal alkaloids first isolated in 2006 from the marine sponge Corticium simplex.  The cortistatins were first discovered in a search for naturally occurring compounds that inhibit proliferation of human umbilical vein endothelial cells (HUVECs), with cortistatin A being the most potent compound in the class.\nThe Shair group at Harvard along with collaborators have shown that cortistatin A is a highly potent and selective inhibitor of CDK8 and CDK19, the kinases that associate with Mediator complex. Out of 386 kinases evaluated, cortistatin A only inhibited CDK8 and CDK19, revealing that it is among the most selective kinase inhibitors. It was also shown that cortistatin A potently inhibits growth of acute myeloid leukemia cells and AML in two in vivo mouse models. Identification of dominant drug-resistant alleles of CDK8 and CDK19 demonstrate that these kinases mediate the activity of cortistatin A in AML cells. Thus, inhibition of CDK8 and CDK19 is a new therapeutic approach to AML. Cortistatin A caused selective and disproportionate up-regulation of super-enhancer-associated genes in AML cells which contributed to its anti-leukemic activity. This work indicated that CDK8 and CDK19 are negative regulators of super-enhancer-associated genes in AML.\nDi-dehydrocortistatin A suppresses viral replication in cells infected with HIV via binding to the Tat protein.\nCortistatin A was synthesized first by Baran, thereafter by Shair, Myers,  and Nicolaou labs."}