Details of the Drug Combination

General Information of Drug Combination (ID: DCTOJ27)

• Drug Combination Name: Bafilomycin A1 + Atovaquone
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Bafilomycin A1 (DMUNK59): Small molecular drug
  Atovaquone (DMY4UMW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 10.868
  Bliss Independence Score: 8.9
  Loewe Additivity Score: 8.931
  LHighest Single Agent (HSA) Score: 9.725

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Bafilomycin A1

Disease Entry	ICD 11	Status	REF
B-cell acute lymphoblastic leukaemia	2B33.3	Investigative	[2]

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	[5]

Bafilomycin A1 Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Expression	[6]
Steroidogenic factor 1 (NR5A1)	OTOULYR4	STF1_HUMAN	Decreases Expression	[7]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Increases Expression	[4]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Decreases Uptake	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[9]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Increases Expression	[10]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Increases Cleavage	[11]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[12]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[4]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Cleavage	[13]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A)	OTPMGIU4	MLP3A_HUMAN	Increases Expression	[14]
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2)	OTLS7C99	LRRK2_HUMAN	Increases Response To Substance	[15]

Indication(s) of Atovaquone

Disease Entry	ICD 11	Status	REF
Fungal infection	1F29-1F2F	Approved	[3]

Atovaquone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[16]

Atovaquone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[17]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica. 2015 Mar;100(3):345-56.
• [3] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [4] 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.
• [5] Molecular basis of V-ATPase inhibition by bafilomycin A1. Nat Commun. 2021 Mar 19;12(1):1782.
• [6] 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.
• [7] Autophagy as a compensation mechanism participates in ethanol-induced fetal adrenal dysfunction in female rats. Toxicol Appl Pharmacol. 2018 Apr 15;345:36-47.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells. Cells. 2019 Mar 12;8(3):235. doi: 10.3390/cells8030235.
• [15] 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.
• [16] Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42.
• [17] Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis. Eur J Clin Pharmacol. 2002 Apr;58(1):19-27.