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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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key FSEZESVJDPKRDS-UWJYYQICSA-N
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
⤷ [5]