Details of the Drug Combination

General Information of Drug Combination (ID: DC5QY71)

• Drug Combination Name: Dorsomorphin + BMS-754807
• Indication: Primitive neuroectodermal tumor; Status: Investigative [1]
• Component Drugs:
  Dorsomorphin (DMKYXJW): Small molecular drug
  BMS-754807 (DMPK32V): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-32
  Zero Interaction Potency (ZIP) Score: 11.72
  Bliss Independence Score: 11.1
  Loewe Additivity Score: 11.5
  LHighest Single Agent (HSA) Score: 19.65

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	[4]

Dorsomorphin Interacts with 23 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bone morphogenetic protein receptor type-1B (BMPR1B)	OTGFN0OD	BMR1B_HUMAN	Increases Expression	[5]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[6]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[7]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[7]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[7]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[6]
Bone morphogenetic protein receptor type-1A (BMPR1A)	OTQOA4ZH	BMR1A_HUMAN	Decreases Expression	[5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[7]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Increases Phosphorylation	[6]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[6]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Decreases Expression	[9]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Decreases Expression	[6]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[7]
Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1)	OT1QHOS2	NF2L1_HUMAN	Decreases Expression	[9]
Methylcytosine dioxygenase TET2 (TET2)	OTKKT03T	TET2_HUMAN	Decreases Expression	[6]
Hemojuvelin (HJV)	OT4235J2	RGMC_HUMAN	Decreases Expression	[5]
Forkhead box protein P3 (FOXP3)	OTA9Z9OC	FOXP3_HUMAN	Decreases Expression	[6]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Decreases Lipidation	[10]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[11]
Transferrin receptor protein 2 (TFR2)	OTMYCCEO	TFR2_HUMAN	Decreases Expression	[5]
Krueppel-like factor 2 (KLF2)	OTIP1UFX	KLF2_HUMAN	Decreases Expression	[12]

BMS-754807 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[13]

BMS-754807 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Response To Substance	[14]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Response To Substance	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Diffuse intrinsic pontine glioma	DCLBIKJ	SU-DIPG-XIII	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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] Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation. Autophagy. 2016 Nov;12(11):2085-2097. doi: 10.1080/15548627.2016.1226733. Epub 2016 Sep 14.
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• [8] 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.
• [9] 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.
• [10] -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.
• [11] 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.
• [12] 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.
• [13] Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in cli... J Med Chem. 2009 Dec 10;52(23):7360-3.
• [14] CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014 Jul 15;74(14):3947-58. doi: 10.1158/0008-5472.CAN-13-2923. Epub 2014 Jul 1.