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
  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 3 (STAT3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[17]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[20]
Cladribine	DM3JDRP	Hairy cell leukaemia	2A82.2	Approved	[21]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[22]

Drug(s) Affected By Signal transducer and activator of transcription 5A (STAT5A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[27]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[28]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[29]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[28]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[30]
Tofacitinib	DMBS370	Rheumatoid arthritis	FA20	Approved	[31]

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	[32]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[33]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[34]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[29]
Tofacitinib	DMBS370	Rheumatoid arthritis	FA20	Approved	[31]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[35]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[36]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[37]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[38]

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 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Post-Translational Modifications	[3]
Signal transducer and activator of transcription 5A (STAT5A)	OTBSJGN3	STA5A_HUMAN	Post-Translational Modifications	[3]
Signal transducer and activator of transcription 5B (STAT5B)	OTZVPEBT	STA5B_HUMAN	Post-Translational Modifications	[3]

References

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• [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.
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• [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).
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• [14] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
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• [22] Quercetin exerts anti-melanoma activities and inhibits STAT3 signaling. Biochem Pharmacol. 2014 Feb 1;87(3):424-34. doi: 10.1016/j.bcp.2013.11.008. Epub 2013 Nov 23.
• [23] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [24] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [25] 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.
• [26] 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.
• [27] Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Mol Pharmacol. 2006 Apr;69(4):1486-91. doi: 10.1124/mol.105.018325. Epub 2006 Jan 24.
• [28] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [29] 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.
• [30] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [36] 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.
• [37] 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.
• [38] 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.