Details of the Drug

General Information of Drug (ID: DMCMH7O)

Drug Name
JNJ-28312141
Synonyms JNJ 28312141
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): 0 Molecular Weight (mw) 460.6
Topological Polar Surface Area (xlogp) 3.1
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C26H32N6O2
IUPAC Name
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide
Canonical SMILES
CN(C)CC(=O)N1CCC(CC1)C2=CC(=C(C=C2)NC(=O)C3=NC=C(N3)C#N)C4=CCCCC4
InChI
InChI=1S/C26H32N6O2/c1-31(2)17-24(33)32-12-10-18(11-13-32)20-8-9-23(22(14-20)19-6-4-3-5-7-19)30-26(34)25-28-16-21(15-27)29-25/h6,8-9,14,16,18H,3-5,7,10-13,17H2,1-2H3,(H,28,29)(H,30,34)
InChIKey
GUBJNPWVIUFSTR-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11676971
CAS Number
885692-52-4
TTD ID
D0Y4BL

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
CSF1R messenger RNA (CSF1R mRNA) TTVW6QL CSF1R_HUMAN Inhibitor [2]
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Inhibitor [1]
LCK tyrosine protein kinase (LCK) TT860QF LCK_HUMAN Inhibitor [1]
NT-3 growth factor receptor (TrkC) TTXABCW NTRK3_HUMAN Inhibitor [1]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_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
NT-3 growth factor receptor (TrkC) DTT NTRK3 7.06E-04 -0.14 -0.43
Tyrosine-protein kinase Kit (KIT) DTT KIT 2.06E-01 -0.1 -0.14
CSF1R messenger RNA (CSF1R mRNA) DTT CSF1R 1.99E-05 0.39 0.56
Fms-like tyrosine kinase 3 (FLT-3) DTT FLT3 2.11E-01 -0.05 -0.16
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol Cancer Ther. 2009 Nov;8(11):3151-61.
2 Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
3 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
4 National Cancer Institute Drug Dictionary (drug id 596693).
5 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
6 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
7 Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
8 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
9 Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
11 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
12 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
13 Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
14 Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part II.Expert Opin Ther Pat. 2017 Jul;27(7):831-849.
15 Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosin... J Biol Chem. 2003 Aug 29;278(35):32892-8.
16 Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16078-83.
17 Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
18 New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
19 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
20 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
21 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
22 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
23 Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
24 National Cancer Institute Drug Dictionary (drug id 452042).
25 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. (Target id: 1807).
26 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
27 Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
28 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)