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

General Information of Drug (ID: DMSCQ9U)

• Drug Name: PD-0173952 Drug Info
• Synonyms: PD173952; PD-173952; TCMDC-137156; 305820-75-1; CHEMBL106772; SCHEMBL3458816; BDBM4213; AC1NS580; DTXSID00416167; HMS3263E07; Tox21_500983; ZINC13812765; NSC735422; CCG-222287; NSC-735422; NCGC00261668-01; PD 173952; FT-0673541; PD173952, > 2-(4-morpholinophenylamino)-6-(2,3-d]pyrimidin-7(8H)-one; 6-(2,6-dichlorophenyl)-8-methyl-2-(4-morpholin-4-ylanilino)pyrido[2,3-d]pyrimidin-7-one; 6-(2,6-Dichlorophenyl)-8-methyl-2-(4-morpholin-4-ylphenylamino)-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: 5328733
  CAS Number: CAS 305820-75-1
  TTD Drug ID: DMSCQ9U

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 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]
Infigratinib	DMNKBEC	Cholangiocarcinoma	2C12.10	Approved	[13]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[14]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	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]
AM-001	DMGVQI8	Actinic keratosis	EK90.0	Phase 2	[19]

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	[20]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[21]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[22]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[23]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[14]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[24]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[26]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[27]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[28]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[29]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[20]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[30]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[14]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[26]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[31]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[32]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[33]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[34]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[3]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[3]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[35]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[36]
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	[37]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[38]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[39]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[40]

Drug(s) Affected By Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (PKMYT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[41]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[42]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[43]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[44]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[45]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[46]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[47]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[47]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[48]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[2]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor 1 (FGFR1)	TTRLW2X	FGFR1_HUMAN	Inhibitor	[1]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[1]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (PKMYT1)	OTYRXD2T	PMYT1_HUMAN	Gene/Protein Processing	[2]

References

• [1] 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.
• [2] Identification of PKMYT1 inhibitors by screening the GSK published protein kinase inhibitor set I and II. Bioorg Med Chem. 2018 Aug 7;26(14):4014-4024. doi: 10.1016/j.bmc.2018.06.027. Epub 2018 Jun 20.
• [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] Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
• [14] 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.
• [15] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029917)
• [20] 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.
• [21] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [22] 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.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [24] 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.
• [25] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [26] National Cancer Institute Drug Dictionary (drug id 452042).
• [27] 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.
• [28] Clinical pipeline report, company report or official report of MedImmune (2011).
• [29] 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.
• [30] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [31] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [32] Company report (Neuronova)
• [33] 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.
• [34] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [35] 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.
• [36] 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.
• [37] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [38] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [39] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [40] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [41] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [42] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [43] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [44] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [45] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [46] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [47] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [48] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.