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

General Information of Drug (ID: DM8RW92)

• Drug Name: PD-0173956 Drug Info
• Synonyms: UNII-YR2DP5GJ1Y; YR2DP5GJ1Y; PD173956; PD-173956; AC1NS9BQ; PD-0173956; 305820-76-2; SCHEMBL1334768; BDBM6569; CHEMBL574059; Pyrido(2,3-d)pyrimidin-7(8H)-one, 6-(2,6-dichlorophenyl)-2-((4-fluorophenyl)amino)-8-methyl-; 6-(2,6-dichlorophenyl)-2-(4-fluoroanilino)-8-methylpyrido[2,3-d]pyrimidin-7-one; 6-(2,6-dichlorophenyl)-2-[(4-fluorophenyl)amino]-8-methyl-7H,8H-pyrido[2,3-d]pyrimidin-7-one

Indication

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

• Cross-matching ID:
  PubChem CID: 5330524
  CAS Number: CAS 305820-76-2
  TTD Drug ID: DM8RW92

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 Fibroblast growth factor receptor 1 (FGFR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[10]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[11]
Pemigatinib	DM819JF	Cholangiocarcinoma	2C12.10	Approved	[12]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[13]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[14]
Rosiglitazone + metformin	DMPIDXT	Diabetic complication	5A2Y	Phase 3	[3]
BGJ398	DMNKBEC	Cholangiocarcinoma	2C12.10	Phase 3	[15]
ARQ-087	DM02BVQ	Intrahepatic cholangiocarcinoma	2C12.10	Phase 3	[16]
AZD4547	DM3827C	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[17]
Debio 1347	DMZW50O	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]

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	[19]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[20]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[21]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[22]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[13]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[23]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[26]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[27]

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	Hepatocellular carcinoma	2C12.02	Approved	[28]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[29]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[30]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[31]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[32]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[20]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]

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	[28]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[19]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[33]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[13]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[34]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[35]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[36]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[37]

Drug(s) Targeting Epidermal growth factor receptor (EGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[38]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[39]
Gefitinib	DM15F0X	Solid tumour/cancer	2A00-2F9Z	Approved	[40]
Erlotinib	DMCMBHA	Non-small-cell lung cancer	2C25.Y	Approved	[41]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[42]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[43]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[44]
Epidermal growth factor	DMVONE6	Vulnerary	ND56.Z	Approved	[42]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[45]

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	[30]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[3]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[44]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[46]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[47]
Flumatinib	DM0G5O6	Chronic myelogenous leukaemia	2A20.0	Phase 2	[48]
DCC-2036	DMJKFNU	Chronic myeloid leukaemia	2A20	Phase 1/2	[49]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[50]
KW-2449	DMFO7RP	Acute myeloid leukaemia	2A60	Phase 1	[51]
PMID27774824-Compound-Figure9Example2down	DMXAV42	N. A.	N. A.	Patented	[52]

Drug(s) Targeting Stress-activated protein kinase 2a (p38 alpha)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[45]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[45]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[53]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[54]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[45]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[55]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[55]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[55]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[55]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[55]

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	[44]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[56]
Al3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[18]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[18]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[57]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[58]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[47]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[59]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[2]
Fibroblast growth factor receptor 1 (FGFR1)	TTRLW2X	FGFR1_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	[1]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]

References

• [1] Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6.
• [2] Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98.
• [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] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [11] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [13] 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.
• [14] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [15] Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
• [16] 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: 1808).
• [17] AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012 Apr 15;72(8):2045-56.
• [18] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [19] 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.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [21] 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.
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [23] 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.
• [24] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [25] National Cancer Institute Drug Dictionary (drug id 452042).
• [26] 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.
• [27] Clinical pipeline report, company report or official report of MedImmune (2011).
• [28] 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.
• [29] 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.
• [30] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [31] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [32] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [33] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [34] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [35] Company report (Neuronova)
• [36] 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.
• [37] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [38] Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
• [39] Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
• [40] Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
• [41] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [42] 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: 1797).
• [43] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [44] 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.
• [45] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [46] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [47] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [48] 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.
• [49] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [50] 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.
• [51] 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.
• [52] 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.
• [53] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
• [54] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [55] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [56] 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.
• [57] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [58] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [59] Clinical pipeline report, company report or official report of Turning Point Therapeutics.