Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMCMH7O)

• Drug Name: JNJ-28312141 Drug Info
• Synonyms: JNJ 28312141

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 11676971
  CAS Number: CAS 885692-52-4
  TTD Drug ID: DMCMH7O

Molecule-Related Drug Atlas

Drug(s) Targeting LCK tyrosine protein kinase (LCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[3]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[5]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[6]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[6]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[6]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[8]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting NT-3 growth factor receptor (TrkC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Entrectinib	DMMPTLH	Non-small-cell lung cancer	2C25	Approved	[10]
Larotrectinib	DM26CQR	Solid tumour/cancer	2A00-2F9Z	Approved	[11]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[12]
Altiratinib	DMUJCBT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
PMID28270021-Compound-WO2016054807Example1	DMD5QEL	Chronic pain	MG30	Patented	[14]
PMID28270010-Compound-Figure24-b	DM0QHLK	N. A.	N. A.	Patented	[13]
Pyrrolo[2,3-d]pyrimidine derivative 4	DME0WSR	Chronic pain	MG30	Patented	[14]
3-amino-5-benzyl-substituted indazole derivative 1	DMFDURZ	Chronic pain	MG30	Patented	[14]
PMID28270010-Compound-Figure5-1	DM2YAPJ	N. A.	N. A.	Patented	[13]
PMID28270021-Compound-WO2015042088Example4	DM6KXOQ	Chronic pain	MG30	Patented	[14]

Drug(s) Targeting CSF1R messenger RNA (CSF1R mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ki-20227	DM9M3VC	Discovery agent	N.A.	Investigative	[2]
GTP-14564	DMW23Y9	Discovery agent	N.A.	Investigative	[15]
GW-2580	DMTW9GM	Discovery agent	N.A.	Investigative	[16]

Drug(s) Targeting Tyrosine-protein kinase Kit (KIT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[3]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[17]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[18]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[19]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[20]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[21]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[22]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]

Drug(s) Targeting Fms-like tyrosine kinase 3 (FLT-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[25]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[26]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[3]
Gilteritinib	DMTI0ZO	Acute myeloid leukaemia	2A60	Approved	[11]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[21]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[25]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[27]
Lestaurtinib	DMQ2AIJ	Acute myeloid leukaemia	2A60	Approved (orphan drug)	[28]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]

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]

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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [28] 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.