General Information of Drug Combination (ID: DC8529N)

Drug Combination Name
Uracil mustard Bendamustine hydrochloride
Indication
Disease Entry Status REF
Melanoma Investigative [1]
Component Drugs Uracil mustard   DMHL7OB Bendamustine hydrochloride   DMFH15Z
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: MALME-3M
Zero Interaction Potency (ZIP) Score: 12.43
Bliss Independence Score: 20.08
Loewe Additivity Score: 14.97
LHighest Single Agent (HSA) Score: 18.7

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Uracil mustard
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [2]
Chronic myelogenous leukaemia 2A20.0 Approved [3]
Polycythemia vera 2A20.4 Approved [3]
Small lymphocytic lymphoma 2A82.0 Approved [3]
Uracil mustard Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [5]
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Uracil mustard Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1) OT7FBG5W NAR1_HUMAN Increases ADR [6]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases ADR [6]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases ADR [6]
Poly polymerase 1 (PARP1) OTIESHK4 PARP1_ARATH Increases ADR [6]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases ADR [6]
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Indication(s) of Bendamustine hydrochloride
Disease Entry ICD 11 Status REF
leukaemia 2A60-2B33 Approved [4]
Bendamustine hydrochloride Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [4]
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Bendamustine hydrochloride Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
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Bendamustine hydrochloride Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Beta-galactosidase (GLB1) OTB0TKAG BGAL_HUMAN Increases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [7]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [7]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [7]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Increases Activity [7]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [7]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Expression [10]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [7]
PRKC apoptosis WT1 regulator protein (PAWR) OTKY7W52 PAWR_HUMAN Decreases Expression [7]
Diablo IAP-binding mitochondrial protein (DIABLO) OTHJ9MCZ DBLOH_HUMAN Increases Localization [7]
Death domain-associated protein 6 (DAXX) OTX6O7PL DAXX_HUMAN Decreases Expression [7]
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⏷ Show the Full List of 13 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCUDGLH MOLT-4 Investigative [11]
Anaplastic large cell lymphoma DCL4PCO SR Investigative [11]
Chronic myelogenous leukemia DCL956D K-562 Investigative [11]
Plasma cell myeloma DCNWNJG RPMI-8226 Investigative [11]
Adenocarcinoma DCSHQB6 A549 Investigative [1]
Adenocarcinoma DCNFXFN HT29 Investigative [1]
Adenocarcinoma DC5MI9A HCT116 Investigative [1]
Adenocarcinoma DCYP0H1 HCT-15 Investigative [1]
Large cell lung carcinoma DCT0K8M NCI-H460 Investigative [1]
Lung adenocarcinoma DCW04KT NCI-H522 Investigative [1]
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⏷ Show the Full List of 10 DrugCom(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
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: 7621).
3 Uracil mustard FDA Label
4 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
5 Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
6 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
7 Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol. 2003 Sep 1;66(5):711-24. doi: 10.1016/s0006-2952(03)00410-6.
8 Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54.
9 Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
10 Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. Leuk Lymphoma. 2004 Jul;45(7):1429-36. doi: 10.1080/1042819042000198858.
11 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.