Details of the Drug Combination

General Information of Drug Combination (ID: DCMI35H)

• Drug Combination Name: AZD2014 + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  AZD2014 (DMOEARH): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 11.23
  Bliss Independence Score: 10.227
  Loewe Additivity Score: 5.805
  LHighest Single Agent (HSA) Score: 8.405

Molecular Interaction Atlas of This Drug Combination

Indication(s) of AZD2014

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]

AZD2014 Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Mammalian target of rapamycin complex 1 (mTORC1)	TTX4GLS	MTOR_HUMAN-RPTOR_HUMAN-LST8_HUMAN-AKTS1_HUMAN-DPTOR_HUMAN	Inhibitor	[9]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[10]
Target of rapamycin complex 2 MAPKAP1 (MTORC2)	TTWDKCL	SIN1_HUMAN	Inhibitor	[9]

AZD2014 Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[11]

AZD2014 Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[12]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[12]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[12]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Affects Expression	[12]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[12]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[3]
High-risk myelofibrosis	2A20.2	Approved	[4]
Myelofibrosis	2A22	Approved	[5]
Myeloproliferative neoplasm	2A20	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]
Pancreatic cancer	2C10	Phase 3	[4]
Atopic dermatitis	EA80	Phase 1/2	[8]
Vitiligo	ED63.0	Phase 1/2	[8]

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	[13]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[13]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[14]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[15]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[15]

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	[16]

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] 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: 7699).
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Ruxolitinib FDA Label
• [7] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12.
• [11] First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 inhibitor AZD2014. Clin Cancer Res. 2015 Aug 1;21(15):3412-9.
• [12] Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
• [13] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [14] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [15] 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.
• [16] 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.