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

General Information of Drug (ID: DMZASMP)

• Drug Name: LY2784544 Drug Info
• Synonyms: LY2784544; 1229236-86-5; GANDOTINIB; LY 2784544; LY-2784544; Gandotinib (LY2784544); UNII-ANC71R916O; LY2784544(Gandotinib); ANC71R916O; 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine; C23H25ClFN7O; 3-[(4-Chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl)imidazo[1,2-b]pyridazin-6-amine; 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[1]
Myeloproliferative neoplasm	2A20	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 46213929
  ChEBI ID: CHEMBL2107823
  CAS Number: CAS 1229236-86-5
  TTD Drug ID: DMZASMP

Molecule-Related Drug Atlas

Drug(s) Targeting Janus kinase 2 (JAK-2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Momelotinib	DMF98Q0	Myelofibrosis	2A20.2	Approved	[4]
Baricitinib	DM4ONW5	Rheumatoid arthritis	FA20	Approved	[5]
Ruxolitinib	DM7Q98D	Essential thrombocythemia	3B63.1Z	Approved	[6]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[7]
Fedratinib	DM4ZBK6	Myelofibrosis	2A20.2	Approved	[8]
ITF2357	DMFZBNE	Duchenne dystrophy	8C70	Phase 3	[9]
XL019	DMJ6F5C	Solid tumour/cancer	2A00-2F9Z	Phase 3	[9]
Cerdulatinib	DMSCR2H	B-cell lymphoma	2A86	Phase 2	[10]
CTP-543	DM3SYOK	Alopecia	ED70	Phase 2	[11]
INCB039110	DMD9RV3	Malignant neoplasm	2A00-2F9Z	Phase 2	[12]

Drug(s) Affected By Myc proto-oncogene protein (MYC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[14]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[15]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[16]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[17]
Selenium	DM25CGV	N. A.	N. A.	Approved	[18]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[19]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[20]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[3]

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: 7909).
• [2] Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J. 2013 Apr 12;3:e109.
• [3] Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors. Eur J Pharmacol. 2015 Oct 15;765:188-97. doi: 10.1016/j.ejphar.2015.08.037. Epub 2015 Aug 20.
• [4] Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis.Leukemia.2015 Mar;29(3):741-4.
• [5] Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
• [6] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [7] National Cancer Institute Drug Dictionary (drug id 609888).
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [9] Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Sep;14(3):471-9.
• [10] Company report (Portola Pharmaceuticals)
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] 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: 2048).
• [13] Acetaminophen-induced proliferation of estrogen-responsive breast cancer cells is associated with increases in c-myc RNA expression and NF-kappaB activity. Toxicol Sci. 2002 Apr;66(2):233-43. doi: 10.1093/toxsci/66.2.233.
• [14] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [15] Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
• [16] ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Mol Cancer Ther. 2007 May;6(5):1579-87. doi: 10.1158/1535-7163.MCT-06-0814.
• [17] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [18] Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr. 2002 Apr;132(4):674-9. doi: 10.1093/jn/132.4.674.
• [19] Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
• [20] Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
• [21] Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Cancer Res. 2002 Nov 1;62(21):6006-10.
• [22] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.