Details of the Drug Combination

General Information of Drug Combination (ID: DC49UIQ)

• Drug Combination Name: Ruxolitinib + Selinexor
• Indication: Myelofibrosis; Status: Phase 3 [1]
• Component Drugs:
  Ruxolitinib (DM7Q98D): Small molecular drug
  Selinexor (DMBD4K3): Small molecular drug

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	[11]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[11]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[12]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[13]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[13]

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	[14]

Indication(s) of Selinexor

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Approved	[4]
Liposarcoma	2B59	Phase 3	[8]
Neuroendocrine cancer	2B72.1	Phase 3	[8]
Acute myeloid leukaemia	2A60	Phase 2	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[9]
Diffuse large B-cell lymphoma	2A81	Phase 2	[2]
Recurrent glioblastoma	2A00.00	Phase 2	[8]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]

Selinexor Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Exportin-1 (XPO1)	TTCJUR4	XPO1_HUMAN	Inhibitor	[15]

Selinexor Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[16]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[16]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[16]

Selinexor Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor protein p73 (TP73)	OT0LUO47	P73_HUMAN	Increases Expression	[17]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[17]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[17]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[17]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[17]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[17]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Multiple Myeloma in Relapse	DC5W7CV	N. A.	Phase 1	[18]

References

• [1] ClinicalTrials.gov (NCT04562389) Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
• [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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] ClinicalTrials.gov (NCT04349098) Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection. U.S. National Institutes of Health.
• [10] ClinicalTrials.gov (NCT02025985) Phase II Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies. U.S. National Institutes of Health.
• [11] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [12] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [13] 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.
• [14] 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.
• [15] Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin Cancer Biol. 2014 August; 0: 62-73.
• [16] FDA label of Selinexor. The 2020 official website of the U.S. Food and Drug Administration.
• [17] The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression. Sci Rep. 2023 Oct 29;13(1):18554. doi: 10.1038/s41598-023-45721-z.
• [18] ClinicalTrials.gov (NCT06225310) A Trial of Selinexor, Ruxolitinib and Methylprednisolone