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

General Information of Drug (ID: DMQ8E9R)

• Drug Name: SKI-758 Drug Info
• Synonyms: SCHEMBL3992463; CHEMBL219557; BDBM13047; SKI-758; 3-quinolinecarbonitrile analog 10; ANUHLKPVOXDYSK-UHFFFAOYSA-N; 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{5-[(4-methylpiperazin-1-yl)methyl]furan-3-yl}quinoline-3-carbonitrile; 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6 methoxy-7-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}-3-quinolinecarbonitrile

Indication

Disease Entry	ICD 11	Status	REF
Ischemia	8B10-8B11	Approved	[1] , [2]

• Cross-matching ID:
  PubChem CID: 11341869
  TTD Drug ID: DMQ8E9R

Molecule-Related Drug Atlas

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	[4]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[5]
Gefitinib	DM15F0X	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Erlotinib	DMCMBHA	Non-small-cell lung cancer	2C25.Y	Approved	[7]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[9]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[10]
Epidermal growth factor	DMVONE6	Vulnerary	ND56.Z	Approved	[9]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[11]
Nitroglycerin	DMQ2491	Angina pectoris	BA40	Approved	[12]

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	[2]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[8]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[13]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[14]
Flumatinib	DM0G5O6	Chronic myelogenous leukaemia	2A20.0	Phase 2	[15]
DCC-2036	DMJKFNU	Chronic myeloid leukaemia	2A20	Phase 1/2	[16]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[17]
KW-2449	DMFO7RP	Acute myeloid leukaemia	2A60	Phase 1	[18]
PMID27774824-Compound-Figure9Example2down	DMXAV42	N. A.	N. A.	Patented	[19]
PMID27774824-Compound-Figure9Example2up	DME3TMS	N. A.	N. A.	Patented	[19]

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	[8]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[8]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[20]
Al3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[21]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[21]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[22]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[23]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[14]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[24]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[25]

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	[3]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[3]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[3]

References

• [1] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] 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.
• [4] Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
• [5] 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.
• [6] Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
• [7] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [8] 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.
• [9] 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).
• [10] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [11] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [12] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [13] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [14] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [15] 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.
• [16] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [24] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [25] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.