General Information of Drug Combination (ID: DC5QY71)

Drug Combination Name
Dorsomorphin BMS-754807
Indication
Disease Entry Status REF
Primitive neuroectodermal tumor Investigative [1]
Component Drugs Dorsomorphin   DMKYXJW BMS-754807   DMPK32V
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
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

Molecular Interaction Atlas (MIA)
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]
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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 [5]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [5]
Forkhead box protein O1 (FOXO1) OTPJRB6D FOXO1_HUMAN Decreases Expression [6]
Bone morphogenetic protein receptor type-1B (BMPR1B) OTGFN0OD BMR1B_HUMAN Increases Expression [7]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) OTVT4YA1 ATG7_HUMAN Increases Expression [8]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [9]
Transferrin receptor protein 1 (TFRC) OT8ZPBDL TFR1_HUMAN Decreases Expression [7]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [8]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [9]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
Bone morphogenetic protein receptor type-1A (BMPR1A) OTQOA4ZH BMR1A_HUMAN Decreases Expression [7]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [9]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Increases Phosphorylation [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [9]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [8]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Increases Phosphorylation [8]
Hepcidin (HAMP) OT607RBL HEPC_HUMAN Decreases Expression [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [9]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [8]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Decreases Expression [11]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) OT7TNF0L AAPK1_HUMAN Decreases Expression [8]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [9]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [8]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Decreases Expression [12]
Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1) OT1QHOS2 NF2L1_HUMAN Decreases Expression [11]
Methylcytosine dioxygenase TET2 (TET2) OTKKT03T TET2_HUMAN Decreases Expression [8]
Hemojuvelin (HJV) OT4235J2 RGMC_HUMAN Decreases Expression [7]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [13]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Decreases Expression [8]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Decreases Lipidation [12]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [14]
Transferrin receptor protein 2 (TFR2) OTMYCCEO TFR2_HUMAN Decreases Expression [7]
Krueppel-like factor 2 (KLF2) OTIP1UFX KLF2_HUMAN Decreases Expression [15]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [9]
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⏷ Show the Full List of 39 DOT(s)
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 [16]
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BMS-754807 Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [17]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Phosphorylation [17]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [17]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Response To Substance [17]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Response To Substance [17]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [17]
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⏷ Show the Full List of 6 DOT(s)

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]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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.
4 The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular a... Bioorg Med Chem Lett. 2010 Nov 15;20(22):6394-9.
5 Reversal of P-glycoprotein-mediated multidrug resistance is induced by mollugin in MCF-7/adriamycin cells. Phytomedicine. 2013 May 15;20(7):622-31.
6 AMP-activated protein kinase mediates the antioxidant effects of resveratrol through regulation of the transcription factor FoxO1. FEBS J. 2014 Oct;281(19):4421-38.
7 A HAMP promoter bioassay system for identifying chemical compounds that modulate hepcidin expression. Exp Hematol. 2015 May;43(5):404-413.e5. doi: 10.1016/j.exphem.2015.01.005. Epub 2015 Jan 26.
8 Compound C induces autophagy and apoptosis in parental and hydroquinone-selected malignant leukemia cells through the ROS/p38 MAPK/AMPK/TET2/FOXP3 axis. Cell Biol Toxicol. 2020 Aug;36(4):315-331. doi: 10.1007/s10565-019-09495-3. Epub 2020 Jan 3.
9 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.
10 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.
11 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.
12 -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.
13 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.
14 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.
15 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.
16 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.
17 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.