Details of the Drug Combination

General Information of Drug Combination (ID: DCS5M9R)

• Drug Combination Name: Dorsomorphin + RTB101
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Dorsomorphin (DMKYXJW): Small molecular drug
  RTB101 (DM62QTW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 4.574
  Bliss Independence Score: 8.615
  Loewe Additivity Score: 6.619
  LHighest Single Agent (HSA) Score: 7.306

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dorsomorphin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Dorsomorphin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
AMP-activated protein kinase (AMPK)	TTLAFZV	AAPK1_HUMAN; AAKB1_HUMAN; AAKG1_HUMAN	Inhibitor	[6]

Dorsomorphin Interacts with 39 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclic AMP-responsive element-binding protein 1 (CREB1)	OT1MDLA1	CREB1_HUMAN	Increases Phosphorylation	[7]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[7]
Forkhead box protein O1 (FOXO1)	OTPJRB6D	FOXO1_HUMAN	Decreases Expression	[8]
Bone morphogenetic protein receptor type-1B (BMPR1B)	OTGFN0OD	BMR1B_HUMAN	Increases Expression	[9]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[10]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[11]
Transferrin receptor protein 1 (TFRC)	OT8ZPBDL	TFR1_HUMAN	Decreases Expression	[9]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[12]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[11]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[10]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[10]
Bone morphogenetic protein receptor type-1A (BMPR1A)	OTQOA4ZH	BMR1A_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[11]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Increases Phosphorylation	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[11]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[10]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Increases Phosphorylation	[10]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Decreases Expression	[9]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[11]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[10]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[10]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Decreases Expression	[13]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Decreases Expression	[10]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[11]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[10]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Decreases Expression	[14]
Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1)	OT1QHOS2	NF2L1_HUMAN	Decreases Expression	[13]
Methylcytosine dioxygenase TET2 (TET2)	OTKKT03T	TET2_HUMAN	Decreases Expression	[10]
Hemojuvelin (HJV)	OT4235J2	RGMC_HUMAN	Decreases Expression	[9]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[15]
Forkhead box protein P3 (FOXP3)	OTA9Z9OC	FOXP3_HUMAN	Decreases Expression	[10]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Decreases Lipidation	[14]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[16]
Transferrin receptor protein 2 (TFR2)	OTMYCCEO	TFR2_HUMAN	Decreases Expression	[9]
Krueppel-like factor 2 (KLF2)	OTIP1UFX	KLF2_HUMAN	Decreases Expression	[17]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[11]

Indication(s) of RTB101

Disease Entry	ICD 11	Status	REF
Respiratory tract infection	CA45	Phase 3	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

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	[18]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Primitive neuroectodermal tumor	DCPY0K2	TC-32	Investigative	[1]

References

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• [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: 4907).
• [3] ClinicalTrials.gov (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
• [4] 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.
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• [11] p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells. Toxicol Appl Pharmacol. 2013 Feb 15;267(1):113-24. doi: 10.1016/j.taap.2012.12.016. Epub 2012 Dec 27.
• [12] Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle cells. Diabetologia. 2012 Nov;55(11):3051-60. doi: 10.1007/s00125-012-2691-1. Epub 2012 Aug 17.
• [13] Metformin leads to accumulation of reactive oxygen species by inhibiting the NFE2L1 expression in human hepatocellular carcinoma cells. Toxicol Appl Pharmacol. 2021 Jun 1;420:115523. doi: 10.1016/j.taap.2021.115523. Epub 2021 Apr 8.
• [14] -amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes. Toxicol Lett. 2023 Jul 1;383:89-97. doi: 10.1016/j.toxlet.2023.06.004. Epub 2023 Jun 16.
• [15] Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway. Mol Nutr Food Res. 2015 Aug;59(8):1443-57. doi: 10.1002/mnfr.201500016. Epub 2015 May 28.
• [16] A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
• [17] Activation of SIRT1 by resveratrol induces KLF2 expression conferring an endothelial vasoprotective phenotype. Cardiovasc Res. 2010 Feb 1;85(3):514-9. doi: 10.1093/cvr/cvp337. Epub 2009 Oct 8.
• [18] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.