Details of the Drug Combination

General Information of Drug Combination (ID: DCB26XH)

Drug Combination Name
OSI-027 Acalabrutinib
Indication
Disease Entry Status REF
Diffuse large B cell lymphoma Investigative [1]
Component Drugs OSI-027   DMJX3O8 Acalabrutinib   DM7GCVW
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TMD8
Zero Interaction Potency (ZIP) Score: 8.13
Bliss Independence Score: 8.05
Loewe Additivity Score: 8.8
LHighest Single Agent (HSA) Score: 11.49

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of OSI-027
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Phase 2 [2]
OSI-027 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [7]
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Indication(s) of Acalabrutinib
Disease Entry ICD 11 Status REF
leukaemia 2A60-2B33 Approved [3]
Mantle cell lymphoma 2A85.5 Approved [4]
Chronic lymphocytic leukaemia 2A82.0 Phase 3 [5]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [6]
Acalabrutinib Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase BTK (ATK) TTGM6VW BTK_HUMAN Inhibitor [4]
HUMAN bruton tyrosine kinase (BTK) TTOWPER BTK_HUMAN Inhibitor [8]
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Acalabrutinib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [9]
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Acalabrutinib Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Affects Expression [10]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [10]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Metabolism [11]
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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 Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol Cancer Ther. 2011 Aug;10(8):1394-406.
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 210259
4 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 ClinicalTrials.gov (NCT04346199) Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.. U.S. National Institutes of Health.
7 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
8 AstraZeneca initiates CALAVI clinical trial with Calquence against COVID-19
9 FDA label of Acalabrutinib. The 2020 official website of the U.S. Food and Drug Administration.
10 Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol. 2020 Jun 5;5(48):eabd0110. doi: 10.1126/sciimmunol.abd0110. Epub 2020 Jun 5.
11 Functional assessment of the effects of CYP3A4 variants on acalabrutinib metabolism in vitro. Chem Biol Interact. 2021 Aug 25;345:109559. doi: 10.1016/j.cbi.2021.109559. Epub 2021 Jun 18.