compound 51 [Mallinger et al., 2016]   Click here for help

GtoPdb Ligand ID: 9170

Compound class: Synthetic organic
Comment: Compound 51 is a potent and selective CDK8/19 inhibitor [3]. It is one of the compounds claimed in patent WO2016009076 [4]. Compound 51 hasa similar inhibitory potency as CCT251545, but is built on a modified chemical scaffold [3]. This is a type I inhibitor, binding in a DMG-in mode.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 99.16
Molecular weight 414.18
XLogP 2.43
No. Lipinski's rules broken 0
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Canonical SMILES COC1CN(C1)C(=O)c1ccc2c(n1)c(cnc2N)c1ccc(cc1)c1cnn(c1)C
Isomeric SMILES COC1CN(C1)C(=O)c1ccc2c(n1)c(cnc2N)c1ccc(cc1)c1cnn(c1)C
InChI InChI=1S/C23H22N6O2/c1-28-11-16(9-26-28)14-3-5-15(6-4-14)19-10-25-22(24)18-7-8-20(27-21(18)19)23(30)29-12-17(13-29)31-2/h3-11,17H,12-13H2,1-2H3,(H2,24,25)
1. Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S et al.. (2008)
CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity.
Nature, 455 (7212): 547-51. [PMID:18794900]
2. Kapoor A, Goldberg MS, Cumberland LK, Ratnakumar K, Segura MF, Emanuel PO, Menendez S, Vardabasso C, Leroy G, Vidal CI et al.. (2010)
The histone variant macroH2A suppresses melanoma progression through regulation of CDK8.
Nature, 468 (7327): 1105-9. [PMID:21179167]
3. Mallinger A, Schiemann K, Rink C, Sejberg J, Honey MA, Czodrowski P, Stubbs M, Poeschke O, Busch M, Schneider R et al.. (2016)
2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19.
ACS Med Chem Lett, 7 (6): 573-8. [PMID:27326329]
4. Schiemann K, Blagg J, Mallinger A, Rink C, Sejberg J, Honey M. (2016)
Novel naphthryidines and isoquinolines and their use as cdk8/19 inhibitors.
Patent number: WO2016009076. Assignee: Merck Patent Gmbh, Cancer Research Technology Limited. Priority date: 17/07/2014. Publication date: 21/01/2016.