Details of the Drug Combination

General Information of Drug Combination (ID: DCOYZ54)

Drug Combination Name
Trametinib Venetoclax
Indication
Disease Entry Status REF
Recurrent Acute Myeloid Leukemia Phase 2 [1]
Component Drugs Trametinib   DM2JGQ3 Venetoclax   DM8I94Y
Small molecular drug 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 Trametinib
Disease Entry ICD 11 Status REF
Melanoma 2C30 Approved [2]
Metastatic melanoma 2E2Z Approved [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [4]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [4]
Trametinib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [5]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [4]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [4]
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Trametinib Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [6]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [6]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [6]
Tumor necrosis factor receptor superfamily member 16 (NGFR) OTPKSM49 TNR16_HUMAN Increases Expression [7]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [6]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [6]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [6]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [6]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Increases Phosphorylation [8]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [7]
Guanine nucleotide-binding protein subunit alpha-11 (GNA11) OT0K99TO GNA11_HUMAN Increases Response To Substance [6]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Response To Substance [9]
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) OTOODWTU GNAQ_HUMAN Increases Response To Substance [6]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Venetoclax
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [3]
Venetoclax Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
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Venetoclax Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Activity [12]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [13]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Folding [14]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [14]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [13]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [14]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Affects Folding [14]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Binding [15]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Affects Response To Substance [16]
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⏷ Show the Full List of 11 DOT(s)

References

1 ClinicalTrials.gov (NCT04487106) Azacitidine, Venetoclax, and Trametinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndrome
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: 6495).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
5 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
6 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
7 Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma. Br J Dermatol. 2019 Feb;180(2):346-356. doi: 10.1111/bjd.17333. Epub 2018 Nov 25.
8 Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway. Toxicol Appl Pharmacol. 2020 Dec 1;408:115273. doi: 10.1016/j.taap.2020.115273. Epub 2020 Oct 6.
9 Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis. Pediatr Blood Cancer. 2018 Sep;65(9):e27237. doi: 10.1002/pbc.27237. Epub 2018 May 16.
10 Venclexta FDA label
11 ZCL-082, a boron-containing compound, induces apoptosis of non-Hodgkin's lymphoma via targeting p90 ribosomal S6 kinase 1/NF-B signaling pathway. Chem Biol Interact. 2022 Jan 5;351:109770. doi: 10.1016/j.cbi.2021.109770. Epub 2021 Nov 30.
12 Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nat Genet. 2015 Sep;47(9):1020-1029. doi: 10.1038/ng.3362. Epub 2015 Jul 27.
13 HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia. Curr Issues Mol Biol. 2023 Aug 23;45(9):7011-7026. doi: 10.3390/cimb45090443.
14 Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells. Blood Cancer J. 2019 Jan 15;9(2):4. doi: 10.1038/s41408-018-0165-5.
15 Prospective Drug Candidates as Human Multidrug Transporter ABCG2 Inhibitors: an In Silico Drug Discovery Study. Cell Biochem Biophys. 2021 Jun;79(2):189-200. doi: 10.1007/s12013-021-00985-y. Epub 2021 May 5.
16 Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors. Cancer Res Commun. 2023 Dec 8;3(12):2497-2509. doi: 10.1158/2767-9764.CRC-23-0350.