General Information of Drug Combination (ID: DCCEXIL)

Drug Combination Name
Evacetrapib Bafilomycin A1
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Evacetrapib   DMCDZ15 Bafilomycin A1   DMUNK59
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 1.91
Bliss Independence Score: 3.1
Loewe Additivity Score: 2.96
LHighest Single Agent (HSA) Score: 5.15

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Evacetrapib
Disease Entry ICD 11 Status REF
Cardiovascular disease BA00-BE2Z Phase 3 [2]
Evacetrapib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cholesteryl ester transfer protein (CETP) TTFQAYR CETP_HUMAN Inhibitor [4]
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Evacetrapib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [5]
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Indication(s) of Bafilomycin A1
Disease Entry ICD 11 Status REF
B-cell acute lymphoblastic leukaemia 2B33.3 Investigative [3]
Bafilomycin A1 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vacuolar-type proton ATPase (v-ATPase) TTTK3BH NOUNIPROTAC Inhibitor [7]
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Bafilomycin A1 Interacts with 24 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptotic protease-activating factor 1 (APAF1) OTJWIVY0 APAF_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Expression [8]
Steroidogenic factor 1 (NR5A1) OTOULYR4 STF1_HUMAN Decreases Expression [9]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [10]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Increases Expression [6]
Albumin (ALB) OTVMM513 ALBU_HUMAN Decreases Uptake [11]
Cathepsin D (CTSD) OTQZ36F3 CATD_HUMAN Decreases Cleavage [12]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Decreases Cleavage [12]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Decreases Expression [13]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [14]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Increases Expression [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Activity [16]
Caspase-4 (CASP4) OTVQTV1L CASP4_HUMAN Increases Activity [17]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Increases Expression [18]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Decreases Activity [16]
BH3-interacting domain death agonist (BID) OTOSHSHU BID_HUMAN Increases Cleavage [19]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) OT4SO7J4 BNIP3_HUMAN Increases Expression [16]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [20]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [16]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) OTZM6MHU NLRP3_HUMAN Increases Expression [6]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Cleavage [21]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) OTPMGIU4 MLP3A_HUMAN Increases Expression [22]
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) OTLS7C99 LRRK2_HUMAN Increases Response To Substance [23]
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⏷ Show the Full List of 24 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 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: 8401).
3 Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica. 2015 Mar;100(3):345-56.
4 The dyslipidaemia market. Nat Rev Drug Discov. 2014 Nov;13(11):807-8.
5 Identification of cytochrome P450 enzymes involved in the metabolism of 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomes. Xenobiotica. 2003 Oct;33(10):989-98.
6 Autophagy mediates bronchial cell malignant transformation induced by chronic arsenic exposure via MEK/ERK1/2 pathway. Toxicol Lett. 2020 Oct 10;332:155-163. doi: 10.1016/j.toxlet.2020.06.006. Epub 2020 Jul 6.
7 Molecular basis of V-ATPase inhibition by bafilomycin A1. Nat Commun. 2021 Mar 19;12(1):1782.
8 Nano-sized iron particles may induce multiple pathways of cell death following generation of mistranscripted RNA in human corneal epithelial cells. Toxicol In Vitro. 2017 Aug;42:348-357.
9 Autophagy as a compensation mechanism participates in ethanol-induced fetal adrenal dysfunction in female rats. Toxicol Appl Pharmacol. 2018 Apr 15;345:36-47.
10 Vitamin D protects against particles-caused lung injury through induction of autophagy in an Nrf2-dependent manner. Environ Toxicol. 2019 May;34(5):594-609.
11 Chronic high glucose inhibits albumin reabsorption by lysosomal alkalinization in cultured porcine proximal tubular epithelial cells (LLC-PK1). Diabetes Res Clin Pract. 2006 Jun;72(3):223-30. doi: 10.1016/j.diabres.2005.10.019. Epub 2005 Nov 28.
12 Berbamine Hydrochloride inhibits lysosomal acidification by activating Nox2 to potentiate chemotherapy-induced apoptosis via the ROS-MAPK pathway in human lung carcinoma cells. Cell Biol Toxicol. 2023 Aug;39(4):1297-1317. doi: 10.1007/s10565-022-09756-8. Epub 2022 Sep 7.
13 SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. Oncotarget. 2018 May 1;9(33):23149-23163. doi: 10.18632/oncotarget.25234. eCollection 2018 May 1.
14 5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells. Toxicol Appl Pharmacol. 2011 Aug 1;254(3):288-98. doi: 10.1016/j.taap.2011.05.003. Epub 2011 May 15.
15 GJA1 reverses arsenic-induced EMT via modulating MAPK/ERK signaling pathway. Toxicol Appl Pharmacol. 2022 Sep 1;450:116138. doi: 10.1016/j.taap.2022.116138. Epub 2022 Jun 21.
16 Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells. Toxicol Appl Pharmacol. 2015 Aug 15;287(1):17-25. doi: 10.1016/j.taap.2015.05.001. Epub 2015 May 14.
17 Autophagy induction by capsaicin in malignant human breast cells is modulated by p38 and extracellular signal-regulated mitogen-activated protein kinases and retards cell death by suppressing endoplasmic reticulum stress-mediated apoptosis. Mol Pharmacol. 2010 Jul;78(1):114-25. doi: 10.1124/mol.110.063495. Epub 2010 Apr 6.
18 Cadmium induces triglyceride levels via microsomal triglyceride transfer protein (MTTP) accumulation caused by lysosomal deacidification regulated by endoplasmic reticulum (ER) Ca(2+) homeostasis. Chem Biol Interact. 2021 Oct 1;348:109649. doi: 10.1016/j.cbi.2021.109649. Epub 2021 Sep 10.
19 Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
20 Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease. Neurosignals. 2011;19(3):163-74. doi: 10.1159/000328516. Epub 2011 Jul 22.
21 LncRNA UCA1 attenuates autophagy-dependent cell death through blocking autophagic flux under arsenic stress. Toxicol Lett. 2018 Mar 1;284:195-204. doi: 10.1016/j.toxlet.2017.12.009. Epub 2017 Dec 15.
22 Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells. Cells. 2019 Mar 12;8(3):235. doi: 10.3390/cells8030235.
23 G2019S LRRK2 mutant fibroblasts from Parkinson's disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy. Toxicology. 2014 Oct 3;324:1-9. doi: 10.1016/j.tox.2014.07.001. Epub 2014 Jul 10.