Details of the Drug Combination

General Information of Drug Combination (ID: DC1Z5DE)

• Drug Combination Name: Cabazitaxel + Lenalidomide
• Indication: Renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Lenalidomide (DM6Q7U4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SN12C
  Zero Interaction Potency (ZIP) Score: 8.82
  Bliss Independence Score: 9.89
  Loewe Additivity Score: 3.6
  LHighest Single Agent (HSA) Score: 12.47

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Metastatic prostate carcinoma	N.A.	Investigative	[3]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[7]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[9]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[9]

Indication(s) of Lenalidomide

Disease Entry	ICD 11	Status	REF
Adult T-cell leukemia/lymphoma	N.A.	Approved	[4]
Advanced cancer	2A00-2F9Z	Approved	[4]
Complex regional pain syndrome type 1	N.A.	Approved	[4]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[4]
Large granular lymphocytic leukemia	2A90.1	Approved	[4]
Leukemia	N.A.	Approved	[4]
MALT lymphoma	N.A.	Approved	[4]
Multiple myeloma	2A83	Approved	[5]
Nodal marginal zone lymphoma	2A85.0	Approved	[4]
Pain	MG30-MG3Z	Approved	[4]
Plasma cell myeloma	2A83.1	Approved	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[4]
Prolymphocytic leukaemia	2A82.1	Approved	[4]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[4]
Small intestine lymphoma	N.A.	Approved	[4]
Splenic marginal zone lymphoma	N.A.	Approved	[4]
Testicular lymphoma	N.A.	Approved	[4]
Urinary bladder neoplasm	N.A.	Approved	[4]
Waldenstrom macroglobulinemia	2A85.4	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Colon cancer	2B90.Z	Investigative	[4]

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	[10]

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	[11]

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	[12]
Interleukin-1 receptor type 1 (IL1R1)	OTTU8959	IL1R1_HUMAN	Decreases Expression	[13]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[13]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[13]
Fibroblast growth factor receptor 2 (FGFR2)	OTLOPACK	FGFR2_HUMAN	Decreases Expression	[12]
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Decreases Expression	[12]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Decreases Expression	[13]
TGF-beta receptor type-1 (TGFBR1)	OT40S1SJ	TGFR1_HUMAN	Decreases Expression	[13]
Interleukin-6 receptor subunit beta (IL6ST)	OT1N9C70	IL6RB_HUMAN	Decreases Expression	[13]
Angiopoietin-1 receptor (TEK)	OT78YN57	TIE2_HUMAN	Decreases Expression	[13]
DNA damage-binding protein 1 (DDB1)	OTTR2L3Z	DDB1_HUMAN	Affects Binding	[14]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[15]
Protein cereblon (CRBN)	OTXH9MDC	CRBN_HUMAN	Increases Response To Substance	[16]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCSXHMV	HT29	Investigative	[1]
Anaplastic large cell lymphoma	DCZFRF4	SR	Investigative	[1]
Clear cell renal cell carcinoma	DCI6H51	TK-10	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCA18F5	OVCAR-5	Investigative	[1]
Large cell lung carcinoma	DCM369C	NCI-H460	Investigative	[1]
Prostate carcinoma	DCEJIQP	PC-3	Investigative	[1]
Invasive ductal carcinoma	DCPZ4RQ	BT-549	Investigative	[17]

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: 6798).
• [3] Cabazitaxel FDA Label
• [4] Lenalidomide FDA Label
• [5] 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).
• [6] Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
• [7] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [8] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [9] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
• [10] Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
• [11] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.