CDK inhibitor 4.35   Click here for help

GtoPdb Ligand ID: 10357

Synonyms: LGR4455
PDB Ligand
Compound class: Synthetic organic
Comment: Compound 4.35 is a selective inhibitor of CDKs 2, 5 and 9 [1]. It was designed for potential anti-lymphoma activity. Its cytotoxic effects on lymphoma cell lines are achieved via promotion of apoptosis. The co-crystal structure of 4.35 bound to CDK2/cyclin A2 has been submitted to the PBD with ID 6GVA [2] and this shows that the ligand binds to the kinase active site.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 130.7
Molecular weight 419.19
XLogP 3.52
No. Lipinski's rules broken 0
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Canonical SMILES NCCSc1nc(NCc2ccc(cc2)c2ccccn2)c2c(n1)c(n[nH]2)C(C)C
Isomeric SMILES NCCSc1nc(NCc2ccc(cc2)c2ccccn2)c2c(n1)c(n[nH]2)C(C)C
InChI InChI=1S/C22H25N7S/c1-14(2)18-19-20(29-28-18)21(27-22(26-19)30-12-10-23)25-13-15-6-8-16(9-7-15)17-5-3-4-11-24-17/h3-9,11,14H,10,12-13,23H2,1-2H3,(H,28,29)(H,25,26,27)
Bioactivity Comments
Compound 4.35 exhibits anti-tumour activity in vivo, in cell line xenograft and patient-derived xenograft mouse models [1]. Significant off-target activity was detected at CK1δ and CHK2, and weak inhibition of PAK4, CAMK1 and RSK1 kinases was measured.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
cyclin dependent kinase 1 Hs Inhibitor Inhibition 7.1 pKi - 1
pKi 7.1 (Ki 9x10-8 M) [1]
Description: Inhibition of CDK1/cyclin B1 complex.
cyclin dependent kinase 2 Hs Inhibitor Inhibition 8.2 – 8.7 pIC50 - 1
pIC50 8.7 (IC50 2x10-9 M) [1]
Description: Inhibition of CDK2/cyclin E1 complex.
pIC50 8.2 (IC50 6x10-9 M) [1]
Description: Inhibition of CDK2/cyclin A2 complex.
cyclin dependent kinase 5 Hs Inhibitor Inhibition 7.8 pIC50 - 1
pIC50 7.8 (IC50 1.5x10-8 M) [1]
Description: Inhibition of CDK5/cyclin p25 complex.
cyclin dependent kinase 9 Hs Inhibitor Inhibition 7.6 pIC50 - 1
pIC50 7.6 (IC50 2.5x10-8 M) [1]
Description: Inhibition of CDK9/cyclin T1 complex.
casein kinase 1 delta Hs Inhibitor Inhibition 7.3 pIC50 - 1
pIC50 7.3 (IC50 4.5x10-8 M) [1]
checkpoint kinase 2 Hs Inhibitor Inhibition 6.3 pIC50 - 1
pIC50 6.3 (IC50 5.25x10-7 M) [1]
cyclin dependent kinase 4 Hs Inhibitor Inhibition 6.2 pIC50 - 1
pIC50 6.2 (IC50 6.03x10-7 M) [1]
Description: Inhibition of CDK4/cyclin D1 complex.