Details of the Drug Combination

General Information of Drug Combination (ID: DCCFYMI)

Drug Combination Name
LY2835219 MK-4827
Indication
Disease Entry Status REF
Anatomic Stage I Breast Cancer AJCC v8 Phase 1 [1]
Component Drugs LY2835219   DM93VBZ MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of LY2835219
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Solid tumour/cancer 2A00-2F9Z Phase 3 [3]
LY2835219 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [7]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [7]
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LY2835219 Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [8]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [8]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [8]
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LY2835219 Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
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LY2835219 Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tripeptidyl-peptidase 1 (TPP1) OT2LQ771 TPP1_HUMAN Increases Expression [6]
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Increases Expression [6]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [6]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Expression [6]
G1/S-specific cyclin-E2 (CCNE2) OTBBUKQQ CCNE2_HUMAN Decreases Expression [10]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases Expression [6]
Fibrinogen beta chain (FGB) OT6RKLI9 FIBB_HUMAN Decreases Expression [6]
Fibrinogen gamma chain (FGG) OT5BJSEX FIBG_HUMAN Decreases Expression [6]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Decreases Expression [6]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [10]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [11]
Gamma-enolase (ENO2) OTRODL0T ENOG_HUMAN Increases Expression [6]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [6]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Affects Expression [12]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [10]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Affects Expression [12]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [12]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Decreases Expression [6]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [6]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Expression [12]
Ephrin-B3 (EFNB3) OT12WTXQ EFNB3_HUMAN Decreases Expression [6]
Insulin growth factor-like family member 2 (IGFL2) OT64M0K7 IGFL2_HUMAN Increases Expression [6]
BRCA1-associated RING domain protein 1 (BARD1) OTTC0Z9Y BARD1_HUMAN Decreases Expression [6]
Fanconi anemia group E protein (FANCE) OTKRPBW1 FANCE_HUMAN Decreases Expression [6]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [11]
Transforming acidic coiled-coil-containing protein 3 (TACC3) OTRNEZTA TACC3_HUMAN Decreases Expression [6]
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⏷ Show the Full List of 27 DOT(s)
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [4]
Breast cancer 2C60-2C65 Phase 2 [5]
Ewing sarcoma 2B52 Phase 1 [5]
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 [7]
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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 [13]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [14]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [14]
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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 [15]
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References

1 ClinicalTrials.gov (NCT04481113) Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor Positive HER2 Negative Breast Cancer
2 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
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: 7382).
4 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.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
7 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
8 Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
9 LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]-Abemaciclib.
10 CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1. J Urol. 2016 Mar;195(3):771-9. doi: 10.1016/j.juro.2015.08.082. Epub 2015 Aug 28.
11 Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42. doi: 10.1016/j.bcp.2016.10.015. Epub 2016 Nov 2.
12 In vitro therapeutic effects of abemaciclib on triple-negative breast cancer cells. J Biochem Mol Toxicol. 2021 Sep;35(9):e22858. doi: 10.1002/jbt.22858. Epub 2021 Jul 26.
13 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.
14 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
15 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.