Details of the Drug Combination

General Information of Drug Combination (ID: DC1MHL3)

• Drug Combination Name: Ruxolitinib + Altretamine
• Indication: Adult T acute lymphoblastic leukemia; Status: Investigative [1]
• Component Drugs:
  Ruxolitinib (DM7Q98D): Small molecular drug
  Altretamine (DMKLAYG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MOLT-4
  Zero Interaction Potency (ZIP) Score: 26.1
  Bliss Independence Score: 23.87
  Loewe Additivity Score: 15.55
  LHighest Single Agent (HSA) Score: 21.54

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[2]
High-risk myelofibrosis	2A20.2	Approved	[3]
Myelofibrosis	2A22	Approved	[4]
Myeloproliferative neoplasm	2A20	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Pancreatic cancer	2C10	Phase 3	[3]
Atopic dermatitis	EA80	Phase 1/2	[7]
Vitiligo	ED63.0	Phase 1/2	[7]

Ruxolitinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[9]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[9]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[10]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[11]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[11]

Ruxolitinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[12]

Indication(s) of Altretamine

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Approved	[8]

Altretamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCNOVLZ	HL-60(TB)	Investigative	[1]
Astrocytoma	DC2JSB1	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCOW5N2	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCR3SZ1	K-562	Investigative	[1]
Glioma	DCD6CAV	SF-268	Investigative	[1]
Plasma cell myeloma	DCBYLK1	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DC6V8UW	SN12C	Investigative	[1]
Breast adenocarcinoma	DCQIMER	MDA-MB-468	Investigative	[14]
Carcinoma	DC2L4XL	MCF7	Investigative	[14]
Invasive ductal carcinoma	DCS7TW6	HS 578T	Investigative	[14]
Adenocarcinoma	DCZ4FBF	HCT116	Investigative	[15]
Adenocarcinoma	DC9WLA6	HT29	Investigative	[15]
Adenocarcinoma	DCE26VT	SW-620	Investigative	[15]
Amelanotic melanoma	DCRKJ26	MDA-MB-435	Investigative	[15]
High grade ovarian serous adenocarcinoma	DC20J8R	OVCAR-8	Investigative	[15]
High grade ovarian serous adenocarcinoma	DCAOAOK	OVCAR-5	Investigative	[15]
Large cell lung carcinoma	DCTO64E	NCI-H460	Investigative	[15]
Lung adenocarcinoma	DCFROKN	EKVX	Investigative	[15]
Malignant melanoma	DCRTI4G	LOX IMVI	Investigative	[15]
Melanoma	DCU2QMO	SK-MEL-2	Investigative	[15]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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: 5688).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Ruxolitinib FDA Label
• [6] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] 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: 7112).
• [9] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [10] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [11] The Use of Anti-Inflammatory Drugs in the Treatment of People With Severe Coronavirus Disease 2019 (COVID-19): The Perspectives of Clinical Immunologists From China. Clin Immunol. 2020 May;214:108393.
• [12] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [13] Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agen... Cancer Chemother Pharmacol. 2008 Dec;63(1):19-26.
• [14] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
• [15] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.