MLN0905   Click here for help

GtoPdb Ligand ID: 9402

Synonyms: compound 12c [PMID: 22070629]
Compound class: Synthetic organic
Comment: MLN0905 is an orally bioavailable inhibitor of Polo-like kinase 1 (PLK1) with in vivo antitumour activity [1]. Despite apparent off-target binding in a kinase profile screen, none of these targets would be expected to produce the cellular and pharmacodynamic effects associated with MLN0905, and in fact the phenotype observed with MLN0905 inhibition is consistent with that observed with PLK1 knockdown by RNAi and other PLK1 inhibitors.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 98.06
Molecular weight 486.18
XLogP 3.61
No. Lipinski's rules broken 0
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Canonical SMILES CN(CCCc1cnc(c(c1)Nc1ncc2c(n1)c1ccc(cc1NC(=S)C2)C(F)(F)F)C)C
Isomeric SMILES CN(CCCc1cnc(c(c1)Nc1ncc2c(n1)c1ccc(cc1NC(=S)C2)C(F)(F)F)C)C
InChI InChI=1S/C24H25F3N6S/c1-14-19(9-15(12-28-14)5-4-8-33(2)3)31-23-29-13-16-10-21(34)30-20-11-17(24(25,26)27)6-7-18(20)22(16)32-23/h6-7,9,11-13H,4-5,8,10H2,1-3H3,(H,30,34)(H,29,31,32)
Bioactivity Comments
In an Ambit kinase profile screen of 359 kinases MLN0905 (1μM) inhibited 9 other kinases by ≥90% (PLK3, DCAMKL1, FLT4, LTK, MERTK, PDGFRB, PRKD3, RPS6KA4, ULK2) and many other kinases by ≥65%- see Supporting Information Table 2 for reference [1].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
polo like kinase 1 Hs Inhibitor Inhibition 8.7 pIC50 - 1
pIC50 8.7 (IC50 2x10-9 M) [1]