General Information of Drug Combination (ID: DCY02OX)

Drug Combination Name
Bafilomycin A1 Crizotinib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Bafilomycin A1   DMUNK59 Crizotinib   DM4F29C
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: 2.57
Bliss Independence Score: 6.39
Loewe Additivity Score: 1.98
LHighest Single Agent (HSA) Score: 3.8

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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]
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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]
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⏷ Show the Full List of 14 DOT(s)
Indication(s) of Crizotinib
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [3]
Crizotinib Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proto-oncogene c-Met (MET) TTNDSF4 MET_HUMAN Modulator [19]
ALK tyrosine kinase receptor (ALK) TTPMQSO ALK_HUMAN Modulator [19]
Proto-oncogene c-Ros (ROS1) TTSZ6Y3 ROS1_HUMAN Modulator [19]
HGF/Met signaling pathway (HGF/Met pathway) TTKA5LP NOUNIPROTAC Inhibitor [20]
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Crizotinib Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [21]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [22]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [22]
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Crizotinib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [23]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [23]
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Crizotinib Interacts with 24 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [24]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Response To Substance [17]
CD44 antigen (CD44) OT9TTJ41 CD44_HUMAN Decreases Expression [16]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Decreases Expression [16]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Increases Expression [25]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [25]
Sterol regulatory element-binding protein 2 (SREBF2) OTBXUNPL SRBP2_HUMAN Increases Expression [25]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [25]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C) OT6KFNMS CAC1C_HUMAN Decreases Activity [25]
Sodium channel protein type 5 subunit alpha (SCN5A) OTGYZWR6 SCN5A_HUMAN Decreases Activity [25]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [17]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [17]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Decreases Secretion [26]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Decreases Secretion [26]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Activity [27]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [28]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [28]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [29]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [29]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1) OTZRWTGA IQGA1_HUMAN Decreases Phosphorylation [30]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [31]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Expression [17]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [24]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Response To Substance [32]
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⏷ Show the Full List of 24 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica. 2015 Mar;100(3):345-56.
3 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: 4903).
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.
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16 Enhancement of the antiproliferative activity of gemcitabine by modulation of c-Met pathway in pancreatic cancer. Curr Pharm Des. 2013;19(5):940-50.
17 Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
18 Aberrant expression of the transcriptional factor Twist1 promotes invasiveness in ALK-positive anaplastic large cell lymphoma. Cell Signal. 2012 Apr;24(4):852-8. doi: 10.1016/j.cellsig.2011.11.020. Epub 2011 Dec 8.
19 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
20 Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma.Drug Des Devel Ther. 2015 Aug 26;9:4897-907.
21 Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Int J Cancer. 2014 Mar 15;134(6):1484-94.
22 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
23 Crizotinib for the treatment of non-small-cell lung cancer. Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7.
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25 Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):245-55.
26 Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012 Nov 1;118(21):5302-9. doi: 10.1002/cncr.27450. Epub 2012 Apr 4.
27 Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem. 2011 Sep 22;54(18):6342-63. doi: 10.1021/jm2007613. Epub 2011 Aug 18.
28 ROS-dependent DNA damage contributes to crizotinib-induced hepatotoxicity via the apoptotic pathway. Toxicol Appl Pharmacol. 2019 Nov 15;383:114768. doi: 10.1016/j.taap.2019.114768. Epub 2019 Oct 19.
29 Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. doi: 10.1073/pnas.1019559108. Epub 2011 Apr 18.
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32 Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17. doi: 10.1126/scitranslmed.3003316. Epub 2012 Jan 25.