Details of the Drug Combination

General Information of Drug Combination (ID: DCW428S)

Drug Combination Name
AL3818 MK-4827
Indication
Disease Entry Status REF
Platinum-resistant Ovarian Cancer Phase 2 [1]
Component Drugs AL3818   DM3WP0N MK-4827   DMLYGH4
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AL3818
Disease Entry ICD 11 Status REF
Alveolar soft part sarcoma 2A60-2C35 Phase 3 [2]
Leiomyosarcoma 2B58 Phase 3 [2]
Synovial sarcoma 2B5A Phase 3 [2]
Cervical cancer 2C77.0 Phase 1/2 [2]
Endometrial cancer 2C76 Phase 1/2 [2]
Fallopian tube cancer 2C74 Phase 1/2 [2]
Ovarian cancer 2C73 Phase 1/2 [2]
Peritoneal cavity cancer 2C51.Z Phase 1/2 [2]
AL3818 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proto-oncogene c-Src (SRC) TT6PKBN SRC_HUMAN Inhibitor [2]
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AL3818 Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [4]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [4]
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Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [3]
Breast cancer 2C60-2C65 Phase 2 [2]
Ewing sarcoma 2B52 Phase 1 [2]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [5]
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MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [6]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [7]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [7]
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MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [8]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
HER2-negative Breast Cancer DCSZQXT N. A. Phase 1 [9]
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References

1 ClinicalTrials.gov (NCT04376073) Anlotinib and Niraparib Dual Therapy Evaluation in Platinum-resistant Recurrent Ovarian Cancer
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
4 Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018 Sep 19;11(1):120.
5 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
6 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
7 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
8 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
9 ClinicalTrials.gov (NCT04764084) Niraparib Combined With Anlotinib in Homologous Recombination Repair (HRR) Gene-mutated Advanced Solid Tumors