ISA-2011B   Click here for help

GtoPdb Ligand ID: 8444

Compound class: Synthetic organic
Comment: Patent search with this structure reveals SCHEMBL10020974 ID matching a structure (Analogue 1) in patent WO2010149944 [3]. ISA-2011B is being evaluated pre-clinically as a potential anti-prostate cancer therapeutic [5].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 74.87
Molecular weight 423.1
XLogP 2.08
No. Lipinski's rules broken 0
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Canonical SMILES Clc1ccc2c(c1)c(c[nH]2)C1N2C(=O)CN(C(=O)C2Cc2c1cc1OCOc1c2)C
Isomeric SMILES Clc1ccc2c(c1)c(c[nH]2)[C@H]1N2C(=O)CN(C(=O)[C@@H]2Cc2c1cc1OCOc1c2)C
InChI InChI=1S/C22H18ClN3O4/c1-25-9-20(27)26-17(22(25)28)4-11-5-18-19(30-10-29-18)7-13(11)21(26)15-8-24-16-3-2-12(23)6-14(15)16/h2-3,5-8,17,21,24H,4,9-10H2,1H3/t17-,21-/m0/s1
Bioactivity Comments
Data from WO2010149944 indicates that ISA-2011B (eq. Analogue 1) causes apoptotic cell death in PC-3 cells (human prostate cells) with an EC50 of 36µM [3]. The compound downregulates the expression of PIP5K1A [5] and is active in vitro and in in vivo xenografted mice. Kinase profile screening of ISA-2011B across 460 kinases (covering >80% of the human catalytic protein kinome) identified several high affinity targets including PIP5K1A, MAP/microtubule affinity-regulating kinase 1 and 4 (MARK1 and MARK4) [5] and BR serine/threonine kinase 2 (BRSK2) [5].
We have tagged PIP5K1A as the primary molecular target of ISA-2011B based on the target validation experiments reported by Semenas et al (2014) [5].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphatidylinositol-4-phosphate 5-kinase type 1 alpha Primary target of this compound Hs Inhibitor Inhibition - - - 5