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

General Information of Drug (ID: DMLK59M)

• Drug Name: AZD1480 Drug Info
• Synonyms: RET inhibitors

Indication

Disease Entry	ICD 11	Status	REF
Myeloproliferative syndrome	2A22	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 16659841
  ChEBI ID: CHEMBL1231124
  CAS Number: CAS 935666-88-9
  TTD Drug ID: DMLK59M

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 Signal transducer and activator of transcription 5B (STAT5B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[16]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[17]
Tofacitinib	DMBS370	Rheumatoid arthritis	FA20	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[20]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[21]
Progesterone	DMUY35B	Amenorrhea	GA20.0	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
Signal transducer and activator of transcription 5B (STAT5B)	OTZVPEBT	STA5B_HUMAN	Post-Translational Modifications	[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: 5933).
• [2] The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009 Dec 8;16(6):487-97.
• [3] Discovery of 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the Jak/Stat pathway. J Med Chem. 2011 Jan 13;54(1):262-76. doi: 10.1021/jm1011319. Epub 2010 Dec 7.
• [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] Oxidative stress triggers STAT3 tyrosine phosphorylation and nuclear translocation in human lymphocytes. J Biol Chem. 1999 Jun 18;274(25):17580-6. doi: 10.1074/jbc.274.25.17580.
• [14] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [15] Arsenic trioxide down-regulates antiapoptotic genes and induces cell death in mycosis fungoides tumors in a mouse model. Ann Oncol. 2008 Aug;19(8):1488-1494. doi: 10.1093/annonc/mdn056. Epub 2008 Mar 17.
• [16] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [17] BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD. Mol Cancer Ther. 2014 Oct;13(10):2315-27. doi: 10.1158/1535-7163.MCT-14-0258. Epub 2014 Jul 22.
• [18] Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov. 2012 Jul;2(7):591-7. doi: 10.1158/2159-8290.CD-12-0028. Epub 2012 Jun 15.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis. Br J Haematol. 2003 Dec;123(5):933-41. doi: 10.1046/j.1365-2141.2003.04700.x.
• [21] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [22] Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75. Breast Cancer Res Treat. 2005 Nov;94(2):171-83. doi: 10.1007/s10549-005-7726-6.