Details of the Drug Combination

General Information of Drug Combination (ID: DCI41AE)

Drug Combination Name

RTB101 Trametinib

Indication

Disease Entry	Status	REF
Diffuse intrinsic pontine glioma	Investigative	[1]

Component Drugs

RTB101 DM62QTW

Trametinib DM2JGQ3

Small molecular drug

High-throughput Screening Result

Testing Cell Line: SU-DIPG-XIII

Zero Interaction Potency (ZIP) Score: 8.488

Bliss Independence Score: 8.307

Loewe Additivity Score: 11.715

LHighest Single Agent (HSA) Score: 14.407

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of RTB101

Disease Entry	ICD 11	Status	REF
Respiratory tract infection	CA45	Phase 3	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[3]

RTB101 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
CREB-regulated transcription coactivator 1 (TORC1)	TT4GO0F	CRTC1_HUMAN	Inhibitor	[7]
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Indication(s) of Trametinib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[4]
Metastatic melanoma	2E2Z	Approved	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[6]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[6]

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	[8]
HUMAN ERK activator kinase 1 (MEK1)	TTAW3TO	MP2K1_HUMAN	Inhibitor	[6]
HUMAN ERK activator kinase 2 (MEK2)	TTWX403	MP2K2_HUMAN	Inhibitor	[6]
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Trametinib Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[9]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[9]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[9]
Tumor necrosis factor receptor superfamily member 16 (NGFR)	OTPKSM49	TNR16_HUMAN	Increases Expression	[10]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[9]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[9]
Guanine nucleotide-binding protein subunit alpha-11 (GNA11)	OT0K99TO	GNA11_HUMAN	Increases Response To Substance	[9]
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ)	OTOODWTU	GNAQ_HUMAN	Increases Response To Substance	[9]
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⏷ Show the Full List of 8 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Embryonal rhabdomyosarcoma	DCMVQXP	Rh36	Investigative	[11]
Embryonal rhabdomyosarcoma	DCZXVQJ	CTR	Investigative	[11]
Embryonal rhabdomyosarcoma	DCZNA62	RD	Investigative	[11]
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References

1	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2	ClinicalTrials.gov (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
3	ClinicalTrials.gov (NCT04409327) Phase 2 Study to Determine if RTB101 Reduces the Severity of COVID-19 in Older Adults Residing in Nursing Homes. U.S. National Institutes of Health.
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: 6495).
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6	Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
7	Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
8	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
9	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.
10	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.
11	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976