Details of the Drug Combination

General Information of Drug Combination (ID: DC0KFPH)

• Drug Combination Name: Picoplatin + Pomalidomide
• Indication: Clear cell renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Picoplatin (DM0PIY6): Small molecular drug
  Pomalidomide (DMTGBAX): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: CAKI-1
  Zero Interaction Potency (ZIP) Score: 9.96
  Bliss Independence Score: 14.96
  Loewe Additivity Score: 15.12
  LHighest Single Agent (HSA) Score: 15.12

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Picoplatin

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 3	[2]
Ovarian cancer	2C73	Phase 3	[2]
Prostate cancer	2C82.0	Phase 3	[2]
Small-cell lung cancer	2C25.Y	Phase 3	[2]

Indication(s) of Pomalidomide

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[3]
Systemic sclerosis	4A42	Approved	[4]

Pomalidomide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiogenesis/myeloma cell growth (AMCG)	TTDIBYJ	NOUNIPROTAC	Modulator	[5]

Pomalidomide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

Pomalidomide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]

Pomalidomide Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[9]
Erythroid transcription factor (GATA1)	OTX1R7O1	GATA1_HUMAN	Decreases Expression	[9]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Decreases Expression	[9]
Transcription factor PU.1 (SPI1)	OTVCA1D0	SPI1_HUMAN	Increases Expression	[9]
Endothelial transcription factor GATA-2 (GATA2)	OTBP2QQ2	GATA2_HUMAN	Decreases Expression	[9]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Increases Expression	[9]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[9]
CCAAT/enhancer-binding protein delta (CEBPD)	OTNBIPMY	CEBPD_HUMAN	Increases Expression	[9]
Krueppel-like factor 1 (KLF1)	OT1FK08U	KLF1_HUMAN	Decreases Expression	[9]
CCAAT/enhancer-binding protein epsilon (CEBPE)	OTKZA25M	CEBPE_HUMAN	Increases Expression	[9]
Transcription factor NF-E2 45 kDa subunit (NFE2)	OTLM94BI	NFE2_HUMAN	Decreases Expression	[9]
Zinc finger protein Gfi-1b (GFI1B)	OTRDW8YO	GFI1B_HUMAN	Decreases Expression	[9]
Zinc finger protein Gfi-1 (GFI1)	OT9HB9H8	GFI1_HUMAN	Increases Expression	[9]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[10]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Oxidation	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DCIJ7RC	U251	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DC1ZPM9	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCKSW38	786-0	Investigative	[1]
Glioblastoma	DCDGOP1	SNB-75	Investigative	[1]
Glioma	DC2FD0V	SF-539	Investigative	[1]
Glioma	DCZ71RP	SF-295	Investigative	[1]
Renal cell carcinoma	DCNPNEF	SN12C	Investigative	[1]
Colon carcinoma	DC9OD1Y	KM12	Investigative	[12]
Adenocarcinoma	DC4RO2Q	OVCAR3	Investigative	[13]
Adenocarcinoma	DCKIOHH	NCIH23	Investigative	[13]
Adenocarcinoma	DCX9MAV	HCT116	Investigative	[13]
Adenocarcinoma	DCKKTIO	HT29	Investigative	[13]
Amelanotic melanoma	DC9HBXB	M14	Investigative	[13]
Amelanotic melanoma	DCX110E	MDA-MB-435	Investigative	[13]
High grade ovarian serous adenocarcinoma	DCMC1M7	NCI\\/ADR-RES	Investigative	[13]
Lung adenocarcinoma	DCZHC1T	EKVX	Investigative	[13]
Lung adenocarcinoma	DCBTK9L	NCI-H522	Investigative	[13]
Malignant melanoma	DCD72RJ	UACC62	Investigative	[13]
Minimally invasive lung adenocarcinoma	DCK1I2O	NCI-H322M	Investigative	[13]
Mixed endometrioid and clear cell carcinoma	DCZ2YL3	IGROV1	Investigative	[13]
Non-small cell lung carcinoma	DCENK0E	HOP-92	Investigative	[13]
Ovarian serous cystadenocarcinoma	DCDY8F1	SK-OV-3	Investigative	[13]
Pleural epithelioid mesothelioma	DC40SUG	NCI-H226	Investigative	[13]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] ClinicalTrials.gov (NCT00465491) Study of Picoplatin Efficacy After Relapse. U.S. National Institutes of Health.
• [3] Pomalidomide FDA Label
• [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: 7348).
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
• [7] Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
• [8] Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
• [9] Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
• [10] 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.
• [11] Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.
• [12] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [13] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976