General Information of Drug Combination (ID: DCD8JE3)

Drug Combination Name
BMS-754807 GSK618334
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs BMS-754807   DMPK32V GSK618334   DMJPXZ4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SU-DIPG-XIII
Zero Interaction Potency (ZIP) Score: 3.877
Bliss Independence Score: 6.812
Loewe Additivity Score: 0.534
LHighest Single Agent (HSA) Score: 1.308

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [4]
------------------------------------------------------------------------------------
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 [5]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Phosphorylation [5]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [5]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Response To Substance [5]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Response To Substance [5]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [5]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DOT(s)
Indication(s) of GSK618334
Disease Entry ICD 11 Status REF
Drug abuse 6C4G.1Z Phase 1 [2]
Nasopharyngeal carcinoma 2B6B Investigative [3]
GSK618334 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D3 receptor (D3R) TT4C8EA DRD3_HUMAN Antagonist [6]
Sphingosine kinase 1 (SPHK1) TTOHFIY SPHK1_HUMAN Inhibitor [3]
------------------------------------------------------------------------------------
GSK618334 Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 4F2 (CYP4F2) DE3GT9C CP4F2_HUMAN Metabolism [7]
------------------------------------------------------------------------------------
GSK618334 Interacts with 47 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [8]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [8]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1) OTGM06VJ IDI1_HUMAN Increases Expression [8]
Squalene monooxygenase (SQLE) OT0GGRDO ERG1_HUMAN Increases Expression [8]
Cyclin-G2 (CCNG2) OTII38K2 CCNG2_HUMAN Increases Expression [8]
Programmed cell death protein 4 (PDCD4) OTZ6NXUX PDCD4_HUMAN Increases Expression [8]
Kelch-like protein 24 (KLHL24) OTWZSX5C KLH24_HUMAN Increases Expression [8]
Protein FAM200C (FAM200C) OTZOXUEK F200C_HUMAN Increases Expression [8]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [9]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Expression [9]
Catechol O-methyltransferase (COMT) OTPWKTQG COMT_HUMAN Increases Expression [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [9]
C-X-C chemokine receptor type 4 (CXCR4) OTUFSBX2 CXCR4_HUMAN Decreases Expression [9]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [9]
Estrogen receptor beta (ESR2) OTXNR2WQ ESR2_HUMAN Decreases Expression [9]
NPC intracellular cholesterol transporter 1 (NPC1) OTRIPICX NPC1_HUMAN Increases Expression [10]
Ubiquitin-like protein ATG12 (ATG12) OTJRO09Y ATG12_HUMAN Increases Expression [11]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) OTVT4YA1 ATG7_HUMAN Increases Expression [11]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [10]
T-cell surface glycoprotein CD8 alpha chain (CD8A) OTDWQJXK CD8A_HUMAN Decreases Expression [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Phosphorylation [11]
T-cell surface glycoprotein CD3 epsilon chain (CD3E) OT13LE5J CD3E_HUMAN Decreases Expression [12]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [12]
T-cell-specific surface glycoprotein CD28 (CD28) OTT5XJST CD28_HUMAN Decreases Expression [12]
B-lymphocyte antigen CD19 (CD19) OTCPF9NF CD19_HUMAN Decreases Expression [12]
Transcription factor E3 (TFE3) OTM99ZWH TFE3_HUMAN Decreases Phosphorylation [13]
Sphingosine 1-phosphate receptor 1 (S1PR1) OTLTXDQT S1PR1_HUMAN Decreases Activity [14]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [11]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [11]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [11]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Decreases Expression [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [11]
C-C chemokine receptor type 7 (CCR7) OTHFUOYE CCR7_HUMAN Decreases Expression [12]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [11]
C-C chemokine receptor type 4 (CCR4) OT68KZ9B CCR4_HUMAN Decreases Expression [12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [15]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [11]
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) OTC41R1E RIPK1_HUMAN Increases Expression [11]
Histone deacetylase 1 (HDAC1) OTQDNOXZ HDAC1_HUMAN Affects Binding [16]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [11]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Decreases Expression [12]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [11]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3) OT28VBVK ATG3_HUMAN Increases Expression [11]
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) OTL1D484 RIPK3_HUMAN Increases Expression [11]
Sphingosine kinase 2 (SPHK2) OTNFG52M SPHK2_HUMAN Increases Phosphorylation [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 47 DOT(s)

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 ClinicalTrials.gov (NCT00513279) To Investigate If Single Doses Of GSK618334 Are Safe And To Investigate Blood Levels Of GSK618334. U.S. National Institutes of Health.
3 Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma.Oncotarget. 2016 Dec 6;7(49):80586-80598.
4 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.
5 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.
6 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
7 Product information - Gilenya.
8 Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
9 Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells. Toxicol Lett. 2018 Jul;291:77-85.
10 FTY720 stimulates 27-hydroxycholesterol production and confers atheroprotective effects in human primary macrophages. Circ Res. 2010 Mar 5;106(4):720-9. doi: 10.1161/CIRCRESAHA.109.204396. Epub 2010 Jan 7.
11 FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma cells. Toxicol Lett. 2015 Jul 2;236(1):43-59. doi: 10.1016/j.toxlet.2015.04.015. Epub 2015 May 1.
12 Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability. Muscle Nerve. 2017 Dec;56(6):1077-1084. doi: 10.1002/mus.25733. Epub 2017 Aug 29.
13 Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress. J Biol Chem. 2018 Aug 10;293(32):12525-12534. doi: 10.1074/jbc.RA118.003471. Epub 2018 Jun 26.
14 Ceramide in the molecular mechanisms of neuronal cell death. The role of sphingosine-1-phosphate. Mol Neurobiol. 2014 Aug;50(1):26-37. doi: 10.1007/s12035-013-8606-4. Epub 2014 Jan 14.
15 Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation. Toxicol Appl Pharmacol. 2014 Nov 15;281(1):39-47. doi: 10.1016/j.taap.2014.09.006. Epub 2014 Sep 16.
16 Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory. Nat Neurosci. 2014 Jul;17(7):971-80. doi: 10.1038/nn.3728. Epub 2014 May 25.