Details of the Drug Combination

General Information of Drug Combination (ID: DCSFEUK)

Drug Combination Name

Trametinib INCB039110

Indication

Disease Entry	Status	REF
Melanoma	Phase 1	[1]

Component Drugs

Trametinib DM2JGQ3

INCB039110 DMD9RV3

Small molecular drug

2D MOL

3D MOL

3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Trametinib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]
Metastatic melanoma	2E2Z	Approved	[3]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[4]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[4]

Trametinib Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Modulator	[7]
HUMAN ERK activator kinase 1 (MEK1)	TTAW3TO	MP2K1_HUMAN	Inhibitor	[4]
HUMAN ERK activator kinase 2 (MEK2)	TTWX403	MP2K2_HUMAN	Inhibitor	[4]
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Trametinib Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[8]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[8]
Tumor necrosis factor receptor superfamily member 16 (NGFR)	OTPKSM49	TNR16_HUMAN	Increases Expression	[9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[8]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[8]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[8]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[8]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Increases Phosphorylation	[10]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[9]
Guanine nucleotide-binding protein subunit alpha-11 (GNA11)	OT0K99TO	GNA11_HUMAN	Increases Response To Substance	[8]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Decreases Response To Substance	[11]
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ)	OTOODWTU	GNAQ_HUMAN	Increases Response To Substance	[8]
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⏷ Show the Full List of 13 DOT(s)

Indication(s) of INCB039110

Disease Entry	ICD 11	Status	REF
Malignant neoplasm	2A00-2F9Z	Phase 2	[5]
Non-small-cell lung cancer	2C25.Y	Phase 2	[6]

INCB039110 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Inhibitor	[12]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Inhibitor	[13]
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References

1	ClinicalTrials.gov (NCT03272464) INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors.
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: 6495).
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4	Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
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: 8364).
6	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
8	Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
9	Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma. Br J Dermatol. 2019 Feb;180(2):346-356. doi: 10.1111/bjd.17333. Epub 2018 Nov 25.
10	Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway. Toxicol Appl Pharmacol. 2020 Dec 1;408:115273. doi: 10.1016/j.taap.2020.115273. Epub 2020 Oct 6.
11	Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis. Pediatr Blood Cancer. 2018 Sep;65(9):e27237. doi: 10.1002/pbc.27237. Epub 2018 May 16.
12	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: 2048).
13	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: 2047).