Details of the Drug Combination

General Information of Drug Combination (ID: DCHAIVG)

• Drug Combination Name: Selinexor + RG7388
• Indication: Rhabdoid Tumor; Status: Phase 1 [1]
• Component Drugs:
  Selinexor (DMBD4K3): Small molecular drug
  RG7388 (DMF5GZI): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Selinexor

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Approved	[2]
Liposarcoma	2B59	Phase 3	[3]
Neuroendocrine cancer	2B72.1	Phase 3	[3]
Acute myeloid leukaemia	2A60	Phase 2	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
Diffuse large B-cell lymphoma	2A81	Phase 2	[4]
Recurrent glioblastoma	2A00.00	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]

Selinexor Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Exportin-1 (XPO1)	TTCJUR4	XPO1_HUMAN	Inhibitor	[10]

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	[11]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[11]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[11]

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	[12]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[12]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[12]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[12]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[12]

Indication(s) of RG7388

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 3	[7]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
Polycythemia vera	2A20.4	Phase 2	[3]
Haematological malignancy	2B33.Y	Phase 1	[9]

RG7388 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ubiquitin-protein ligase E3 Mdm2 (MDM2)	TT08GJW	MDM2_HUMAN	Modulator	[13]
Erbb4 tyrosine kinase receptor (Erbb-4)	TT0JESD	ERBB4_HUMAN	Inhibitor	[14]

References

• [1] ClinicalTrials.gov (NCT05952687) Trial of Idasanutlin and Selinexor Therapy for Children With Progressive/Relapsed AT/RT or Extra-CNS Malignant Rhabdoid Tumors
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT04349098) Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection. U.S. National Institutes of Health.
• [6] ClinicalTrials.gov (NCT02025985) Phase II Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies. U.S. National Institutes of Health.
• [7] ClinicalTrials.gov (NCT02545283) A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (MIRROS). U.S. National Institutes of Health.
• [8] Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
• [9] ClinicalTrials.gov (NCT02407080) Open Label Study of Single Agent Oral RG7388 in Patients With Polycythemia Vera and Essential Thrombocythemia. U.S. National Institutes of Health.
• [10] Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin Cancer Biol. 2014 August; 0: 62-73.
• [11] FDA label of Selinexor. The 2020 official website of the U.S. Food and Drug Administration.
• [12] 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.
• [13] Pre-clinical evaluation of the MDM2-p53 antagonist RG7388 alone and in combination with chemotherapy in neuroblastoma. Oncotarget. 2015 Apr 30;6(12):10207-21.
• [14] 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: 1799).