General Information of Drug (ID: DMBMYKQ)

Drug Name
PMID22564207C25b
Synonyms CEP-28122; 1022958-60-6; GTPL8139; EX-A1541; ZINC84654307; BDBM50389154; CS-5176; NCGC00387821-03; HY-18030
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 539.1
Topological Polar Surface Area (xlogp) 4.1
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C28H35ClN6O3
IUPAC Name
(1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide
Canonical SMILES
COC1=C(C=CC2=C1CC[C@H](CC2)N3CCOCC3)NC4=NC=C(C(=N4)N[C@@H]5[C@@H]6C[C@H]([C@@H]5C(=O)N)C=C6)Cl
InChI
InChI=1S/C28H35ClN6O3/c1-37-25-20-8-7-19(35-10-12-38-13-11-35)6-4-16(20)5-9-22(25)32-28-31-15-21(29)27(34-28)33-24-18-3-2-17(14-18)23(24)26(30)36/h2-3,5,9,15,17-19,23-24H,4,6-8,10-14H2,1H3,(H2,30,36)(H2,31,32,33,34)/t17-,18+,19+,23+,24-/m1/s1
InChIKey
LAJAFFLJAJMYLK-CVOKMOJFSA-N
Cross-matching ID
PubChem CID
57325421
CAS Number
1431697-87-8
TTD ID
D09AID

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
ALK tyrosine kinase receptor (ALK) TTPMQSO ALK_HUMAN Inhibitor [1]
Omphalocele kinase 1 (NUAK1) TT65FL0 NUAK1_HUMAN Inhibitor [1]
Proto-oncogene c-Fer (FER) TTRA9G0 FER_HUMAN Inhibitor [1]
Proto-oncogene c-Fes (FES) TTLBY21 FES_HUMAN Inhibitor [1]
Ribosomal protein S6 kinase alpha-2 (RSK2) TT0ZW9O KS6A2_HUMAN Inhibitor [1]
Ribosomal protein S6 kinase alpha-3 (RSK3) TTUM2ZR KS6A3_HUMAN Inhibitor [1]
Ribosomal protein S6 kinase alpha-6 (RSK6) TT3KYWB KS6A6_HUMAN Inhibitor [1]
Serine/threonine-protein kinase Chk2 (RAD53) TT9ABMF CHK2_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
ALK tyrosine kinase receptor (ALK) DTT ALK 7.19E-15 0.18 0.61
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
3 BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007 Jan 1;401(1):29-38.
4 The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
5 Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg Med Chem Lett. 2012 Jan 1;22(1):738-42.
6 Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib. J Med Chem.> 2014 Feb 27;57(4):1170-87.
7 Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25.
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9 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
10 Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.
11 Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem. 2005 Mar 24;48(6):1873-85.
12 Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Ther. 2009 Dec;331(3):816-26.
13 CCT241533 Is a Potent and Selective Inhibitor of CHK2 that Potentiates the Cytotoxicity of PARP Inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
14 A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
15 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
16 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
17 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
18 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
19 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7397).
20 CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
21 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
22 PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81.
23 Substituted tetrahydropyrido[3,2:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamides as RSK inhibitors. US9771366.