Details of the Drug Combination

General Information of Drug Combination (ID: DCJED06)

Drug Combination Name
Alvespimycin hydrochloride Omacetaxine mepesuccinate
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Alvespimycin hydrochloride   DM6KU93 Omacetaxine mepesuccinate   DMPU2WX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 13.02
Bliss Independence Score: 10.036
Loewe Additivity Score: 9.136
LHighest Single Agent (HSA) Score: 12.743

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Alvespimycin hydrochloride
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 1 [2]
Refractory hematologic malignancy 2A85.5 Phase 1 [2]
Alvespimycin hydrochloride Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Heat shock protein 90 alpha (HSP90A) TT78R5H HS90A_HUMAN Inhibitor [5]
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Indication(s) of Omacetaxine mepesuccinate
Disease Entry ICD 11 Status REF
Adult acute monocytic leukemia N.A. Approved [3]
Chronic myelogenous leukaemia 2A20.0 Approved [3]
Chronic myeloid leukaemia 2A20 Approved [4]
Leukemia N.A. Approved [3]
Omacetaxine mepesuccinate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ribosome A (hRA) TTA4FIU NOUNIPROTAC Modulator [6]
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Omacetaxine mepesuccinate Interacts with 29 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK) OTLF4ZB1 IKKA_HUMAN Increases Phosphorylation [7]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [7]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Increases Expression [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [9]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [8]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [8]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Increases Expression [8]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
Hematopoietic progenitor cell antigen CD34 (CD34) OT1MOFLZ CD34_HUMAN Decreases Expression [7]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38) OTG0TTX7 CD38_HUMAN Increases Expression [7]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Expression [8]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [8]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [8]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Increases Expression [7]
Ephrin type-B receptor 4 (EPHB4) OTKLPVXJ EPHB4_HUMAN Decreases Expression [8]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Cleavage [8]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [8]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [8]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [7]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [7]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [9]
Jouberin (AHI1) OT8K2YWY AHI1_HUMAN Increases Expression [10]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [8]
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⏷ Show the Full List of 29 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 (NCT00089271) 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas. U.S. National Institutes of Health.
3 Omacetaxine mepesuccinate FDA Label
4 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: 7454).
5 Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jul;51(1):34-41.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
8 Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem Toxicol. 2020 Feb;136:110960. doi: 10.1016/j.fct.2019.110960. Epub 2019 Nov 11.
9 [Homoharringtonine combined arsenic trioxide induced apoptosis in human multiple myeloma cell line RPMI 8226: an experimental research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Jun;33(6):834-9.
10 [Expression and function of Ahi-1 gene in Jurkat cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):445-9.