Details of the Drug Combination

General Information of Drug Combination (ID: DC23AQP)

• Drug Combination Name: Everolimus + Carboplatin
• Indication: Metastatic Melanoma; Status: Phase 2 [1]
• Component Drugs:
  Everolimus (DM8X2EH): Small molecular drug
  Carboplatin (DMG281S): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Everolimus

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[2]
Advanced/metastatic breast cancer	2C60	Approved	[3]
Brainstem neoplasm	N.A.	Approved	[2]
Breast carcinoma	N.A.	Approved	[2]
Graft-versus-host disease	4B24	Approved	[2]
Intracranial meningioma	N.A.	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Mucosal melanoma	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Plasma cell myeloma	2A83.1	Approved	[2]
Prostate cancer	2C82.0	Approved	[2]
Renal cell carcinoma	2C90	Approved	[4]
Salivary gland squamous cell carcinoma	N.A.	Approved	[2]
Tuberous sclerosis	LD2D.2	Approved	[2]
Kidney cancer	2C90.0	Phase 3	[4]
Castration-resistant prostate carcinoma	N.A.	Investigative	[2]
Colon cancer	2B90.Z	Investigative	[2]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[5]
Neuroblastoma	2D11.2	Investigative	[2]
Pancreatic acinar cell carcinoma	N.A.	Investigative	[2]
Polycystic kidney disease	GB8Y	Investigative	[2]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[5]

Everolimus Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[8]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[5]

Everolimus Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Everolimus Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Indication(s) of Carboplatin

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[6]
Carcinoma	2A00-2F9Z	Approved	[6]
Cholangiocarcinoma	2C12.10	Approved	[6]
Cutaneous melanoma	2C30	Approved	[6]
Epithelial ovarian cancer	2B5D	Approved	[6]
Fallopian tube neoplasm	N.A.	Approved	[6]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[6]
Lung adenocarcinoma	N.A.	Approved	[6]
Lung cancer	2C25.0	Approved	[6]
Non-small-cell lung cancer	2C25.Y	Approved	[6]
Ovarian cancer	2C73	Approved	[7]
Ovarian disorder	N.A.	Approved	[6]
Ovarian neoplasm	N.A.	Approved	[6]
Ovarian serous cystadenocarcinoma	N.A.	Approved	[6]
Small-cell lung cancer	2C25.Y	Approved	[6]
Lung large cell carcinoma	N.A.	Investigative	[6]
Neuroblastoma	2D11.2	Investigative	[6]

Carboplatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[11]

Carboplatin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
High affinity copper uptake protein 1 (SLC31A1)	DTP8L4F	COPT1_HUMAN	Substrate	[12]

Carboplatin Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[13]
Glutathione S-transferase theta-1 (GSTT1)	DE3PKUG	GSTT1_HUMAN	Metabolism	[13]
Metallothionein-1A (MT1A)	DE5ME8A	MT1A_HUMAN	Metabolism	[13]
Metallothionein-2A (MT2A)	DEFKGT7	MT2_HUMAN	Metabolism	[13]
Myeloperoxidase (MPO)	DEA3U9Y	PERM_HUMAN	Metabolism	[13]
Quinone reductase 1 (NQO1)	DENP5RY	NQO1_HUMAN	Metabolism	[13]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast Cancer	DCXB8EB	N. A.	Phase 2	[14]
Breast Cancer	DC23FCZ	N. A.	Phase 1	[15]

References

• [1] ClinicalTrials.gov (NCT01014351) Study of Everolimus With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
• [2] Everolimus FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 5889).
• [5] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [6] Carboplatin FDA Label
• [7] 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: 7624).
• [8] Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
• [9] Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
• [10] The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
• [11] Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
• [12] Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
• [13] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [14] ClinicalTrials.gov (NCT02531932) Comparison of Single-Agent Carboplatin vs the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer
• [15] ClinicalTrials.gov (NCT01127763) RAD001 Plus Carboplatin in Breast Cancer Patients