Details of the Drug Combination

General Information of Drug Combination (ID: DCESXKJ)

• Drug Combination Name: Lenalidomide + Cyclosporin A
• Indication: Myelodysplastic Syndrome; Status: Phase 1 [1]
• Component Drugs:
  Lenalidomide (DM6Q7U4): Small molecular drug
  Cyclosporin A (DMUYKBZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lenalidomide

Disease Entry	ICD 11	Status	REF
Adult T-cell leukemia/lymphoma	N.A.	Approved	[2]
Advanced cancer	2A00-2F9Z	Approved	[2]
Complex regional pain syndrome type 1	N.A.	Approved	[2]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[2]
Large granular lymphocytic leukemia	2A90.1	Approved	[2]
Leukemia	N.A.	Approved	[2]
MALT lymphoma	N.A.	Approved	[2]
Multiple myeloma	2A83	Approved	[3]
Nodal marginal zone lymphoma	2A85.0	Approved	[2]
Pain	MG30-MG3Z	Approved	[2]
Plasma cell myeloma	2A83.1	Approved	[2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[2]
Prolymphocytic leukaemia	2A82.1	Approved	[2]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[2]
Small intestine lymphoma	N.A.	Approved	[2]
Splenic marginal zone lymphoma	N.A.	Approved	[2]
Testicular lymphoma	N.A.	Approved	[2]
Urinary bladder neoplasm	N.A.	Approved	[2]
Waldenstrom macroglobulinemia	2A85.4	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Colon cancer	2B90.Z	Investigative	[2]

Lenalidomide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Inhibitor	[15]

Lenalidomide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[16]

Lenalidomide Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Fibroblast growth factor receptor 1 (FGFR1)	OT4GLCXW	FGFR1_HUMAN	Affects Expression	[17]
Interleukin-1 receptor type 1 (IL1R1)	OTTU8959	IL1R1_HUMAN	Decreases Expression	[18]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[18]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[18]
Fibroblast growth factor receptor 2 (FGFR2)	OTLOPACK	FGFR2_HUMAN	Decreases Expression	[17]
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Decreases Expression	[17]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Decreases Expression	[18]
TGF-beta receptor type-1 (TGFBR1)	OT40S1SJ	TGFR1_HUMAN	Decreases Expression	[18]
Interleukin-6 receptor subunit beta (IL6ST)	OT1N9C70	IL6RB_HUMAN	Decreases Expression	[18]
Angiopoietin-1 receptor (TEK)	OT78YN57	TIE2_HUMAN	Decreases Expression	[18]
DNA damage-binding protein 1 (DDB1)	OTTR2L3Z	DDB1_HUMAN	Affects Binding	[19]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[20]
Protein cereblon (CRBN)	OTXH9MDC	CRBN_HUMAN	Increases Response To Substance	[21]

Indication(s) of Cyclosporin A

Disease Entry	ICD 11	Status	REF
Adult acute monocytic leukemia	N.A.	Approved	[5]
Bronchiolitis obliterans syndrome	N.A.	Approved	[6]
Large granular lymphocytic leukemia	2A90.1	Approved	[7]
Leukemia	N.A.	Approved	[8]
Lupus nephritis	4A40.0Y	Approved	[9]
Myeloid leukaemia	2B33.1	Approved	[10]
Psoriasis	EA90	Approved	[11]
Xerophthalmia	5B55.Y	Approved	[12]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[13]
Corneal disease	9A78.Z	Investigative	[14]

References

• [1] ClinicalTrials.gov (NCT00840827) Efficacy and Safety of Lenalidomide in Combination With Cyclosporine A in Patients With Myelodysplastic Syndromes
• [2] Lenalidomide FDA Label
• [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: 7331).
• [4] Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
• [5] Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia. Haematologica. 2023 Jan 1;108(1):61-68.
• [6] Bronchiolitis obliterans syndrome is associated with increased senescent lymphocytes in the small airways. J Heart Lung Transplant. 2021 Feb;40(2):108-119.
• [7] Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series. Semin Arthritis Rheum. 2020 Oct;50(5):1109-1113.
• [8] Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways. Reprod Biol Endocrinol. 2020 Oct 12;18(1):100.
• [9] Efficacy and safety of Iguratimod as an add-on therapy for refractory lupus nephritis: A preliminary investigational study. Front Immunol. 2023 Mar 8;14:1062919.
• [10] Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e127-e135.
• [11] Pustular psoriasis. Cutis. 1993 Jan;51(1):29-32.
• [12] Cyclosporin A (CyA) in primary Sj?gren's syndrome: a double blind study. Ann Rheum Dis. 1986 Sep;45(9):732-5.
• [13] Why Choose Cyclosporin A as First-line Therapy in COVID-19 Pneumonia. Reumatol Clin. 2020 Apr 16;S1699-258X(20)30044-9.
• [14] Anti-inflammatory therapy of dry eye. Ocul Surf. 2003 Jan;1(1):31-6.
• [15] Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
• [16] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
• [17] Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
• [18] Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005 Apr 15;105(8):3286-94. doi: 10.1182/blood-2004-06-2101. Epub 2004 Dec 23.
• [19] Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014 Sep;21(9):803-9. doi: 10.1038/nsmb.2874. Epub 2014 Aug 10.
• [20] Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
• [21] A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.