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

General Information of Drug (ID: DM9GDP5)

• Drug Name: JNJ-10198409 Drug Info
• Synonyms: JNJ-10198409; 627518-40-5; PDGFR Tyrosine Kinase Inhibitor IV; PDGF Receptor Tyrosine Kinase Inhibitor IV; CHEMBL120077; N-(3-fluorophenyl)-6,7-dimethoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-amine; 3-Fluoro-N-(6,7-dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamine; ZDNURMVOKAERHZ-UHFFFAOYSA-N; SCHEMBL3088170; GTPL6020; CTK8E8807; jnj10198409; DTXSID70430890; MolPort-009-019-131; HMS3650O03; HMS3229I11; ZINC13677843; BDBM50179207; AKOS030525202; RWJ 540973; CCG-206773; NCGC00343986-02; RT-014973; KB-274227; SR-01000946814

Indication

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

• Cross-matching ID:
  PubChem CID: 9797370
  CAS Number: CAS 627518-40-5
  TTD Drug ID: DM9GDP5

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	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 Fyn tyrosine protein kinase (FYN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	Approved	[3]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
Ro-4396686	DM5DMCH	Discovery agent	N.A.	Investigative	[11]
PMID15546730C2	DMOPUIH	Discovery agent	N.A.	Investigative	[12]
CEP-5104	DMV43GY	Discovery agent	N.A.	Investigative	[13]
CEP-6331	DMNXBTD	Discovery agent	N.A.	Investigative	[13]
1-Methoxy-2-[2-(2-Methoxy-Ethoxy]-Ethane	DMD7WNV	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting Platelet-derived growth factor receptor alpha (PDGFRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[15]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[16]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[17]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[18]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[19]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[20]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[24]

Drug(s) Targeting Platelet-derived growth factor receptor beta (PDGFRB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[25]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[15]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[26]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[19]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[27]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[28]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[29]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[30]

Drug(s) Targeting Tyrosine-protein kinase ABL1 (ABL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[31]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[3]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[32]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[33]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[34]
Flumatinib	DM0G5O6	Chronic myelogenous leukaemia	2A20.0	Phase 2	[35]
DCC-2036	DMJKFNU	Chronic myeloid leukaemia	2A20	Phase 1/2	[36]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[37]
KW-2449	DMFO7RP	Acute myeloid leukaemia	2A60	Phase 1	[38]
PMID27774824-Compound-Figure9Example2down	DMXAV42	N. A.	N. A.	Patented	[39]

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[3]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[32]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[40]
Al3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[41]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[41]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[42]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[43]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[34]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[44]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fyn tyrosine protein kinase (FYN)	TT2B9KF	FYN_HUMAN	Inhibitor	[2]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[2]
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[2]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[2]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[2]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[2]

References

• [1] 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: 6020).
• [2] (6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad ant... J Med Chem. 2005 Dec 29;48(26):8163-73.
• [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] National Cancer Institute Drug Dictionary (drug id 596693).
• [11] Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3.
• [12] Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6061-6.
• [13] Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-linea... J Med Chem. 2008 Sep 25;51(18):5680-9.
• [14] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [15] Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [17] A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):595-604.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [19] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [20] The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations.Invest New Drugs.2015 Apr;33(2):300-9.
• [21] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [22] National Cancer Institute Drug Dictionary (drug id 452042).
• [23] Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
• [24] Clinical pipeline report, company report or official report of MedImmune (2011).
• [25] 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.
• [26] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [27] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [28] Company report (Neuronova)
• [29] Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. Biochemistry. 2011 Feb 8;50(5):738-51.
• [30] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [31] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [32] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [33] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [34] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [35] Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
• [36] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [37] Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem. 2008 Mar 13;51(5):1252-9.
• [38] KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
• [39] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [40] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [41] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [42] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [43] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [44] Clinical pipeline report, company report or official report of Turning Point Therapeutics.