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

General Information of Drug (ID: DMQDUG4)

• Drug Name: ISIS-CRP Drug Info
• Synonyms: 1-(Tert-butyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; 172889-27-9; pp2; PP 2; 1-(tert-butyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; AG 1879; 1-tert-butyl-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; PP2; 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine; AG-1879; CHEMBL406845; CHEBI:78331; AK-60369; 1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine; 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; C15H16ClN5; 1qpe; 4few; PBBRWFOVCUAONR-UHFFFAOYSA-N; AG1879; PP 2 (AG 1879)

Indication

Disease Entry	ICD 11	Status	REF
Cardiovascular disease	BA00-BE2Z	Phase 1	[1]
Inflammation	1A00-CA43.1	Phase 1	[1]

• Cross-matching ID: TTD Drug ID: DMQDUG4

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	[6]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[8]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[8]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[9]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[8]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[10]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[11]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[8]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS-CRPRx	DML84CN	Coronary artery disease	BA80	Phase 2	[12]
ISIS 133726	DMJ56XU	Discovery agent	N.A.	Investigative	[13]
ISIS 133712	DMDZ3FU	Discovery agent	N.A.	Investigative	[13]
ISIS 140180	DMP9WOZ	Discovery agent	N.A.	Investigative	[13]
ISIS 330031	DM35WFL	Discovery agent	N.A.	Investigative	[13]
ISIS 330012	DMWIVS9	Discovery agent	N.A.	Investigative	[13]
ISIS 329956	DMA96KW	Discovery agent	N.A.	Investigative	[13]
Phosphocholine	DMIZLVW	Discovery agent	N.A.	Investigative	[14]

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	[15]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[6]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[16]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[17]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[18]
Flumatinib	DM0G5O6	Chronic myelogenous leukaemia	2A20.0	Phase 2	[19]
DCC-2036	DMJKFNU	Chronic myeloid leukaemia	2A20	Phase 1/2	[20]
KW-2449	DMFO7RP	Acute myeloid leukaemia	2A60	Phase 1	[21]
PMID27774824-Compound-Figure9Example2down	DMXAV42	N. A.	N. A.	Patented	[22]
PMID27774824-Compound-Figure9Example2up	DME3TMS	N. A.	N. A.	Patented	[22]

Drug(s) Targeting Tyrosine-protein kinase BRK (PTK6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID21855335C19a	DMTKJA9	Discovery agent	N.A.	Investigative	[23]

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	[6]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[6]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[16]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[24]
Al3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[25]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[25]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[26]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[27]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[18]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[28]

Drug(s) Targeting RIP2 messenger RNA (RIP2 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NM-PP1	DMS8H5Q	Discovery agent	N.A.	Investigative	[3]
ISIS 104258	DMUC3L0	Discovery agent	N.A.	Investigative	[29]
ISIS 104254	DMDEI9X	Discovery agent	N.A.	Investigative	[29]
ISIS 104211	DMPKQ61	Discovery agent	N.A.	Investigative	[29]
ISIS 104257	DMSDCGV	Discovery agent	N.A.	Investigative	[29]
ISIS 104256	DMHUX9A	Discovery agent	N.A.	Investigative	[29]
ISIS 104255	DMAI5B8	Discovery agent	N.A.	Investigative	[29]
ISIS 104253	DMME8JP	Discovery agent	N.A.	Investigative	[29]
Src kinase inhibitor I	DMUZP9V	Discovery agent	N.A.	Investigative	[3]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CRP messenger RNA (CRP mRNA)	TTWRN6M	CRP_HUMAN	Not Available	[2] , [1]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[3]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[3]
RIP2 messenger RNA (RIP2 mRNA)	TTCQ2E5	RIPK2_HUMAN	Inhibitor	[3]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[4]
Tyrosine-protein kinase BRK (PTK6)	TT6TH8V	PTK6_HUMAN	Inhibitor	[5]

References

• [1] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
• [2] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
• [3] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [4] 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.
• [5] Inhibition of SRC tyrosine kinase impairs inherent and acquired gemcitabine resistance in human pancreatic adenocarcinoma cells. Clin Cancer Res. 2004 Apr 1;10(7):2307-18.
• [6] 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.
• [7] National Cancer Institute Drug Dictionary (drug id 596693).
• [8] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [9] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [10] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [11] 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.
• [12] Antisense oligonucleotides on neurobehavior, respiratory, and cardiovascular function, and hERG channel current studies. J Pharmacol Toxicol Methods. 2014 Jan-Feb;69(1):49-60.
• [13] US patent application no. 7,425,545, Modulation of C-reactive protein expression.
• [14] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] 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.
• [17] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [18] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [19] 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.
• [20] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [21] 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.
• [22] 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.
• [23] Discovery of novel imidazo[1,2-a]pyrazin-8-amines as Brk/PTK6 inhibitors. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5870-5.
• [24] 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.
• [25] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [26] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [27] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [28] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [29] US patent application no. 6,426,221, Antisense modulation of RIP2 expression.