Details of the Drug Combination

General Information of Drug Combination (ID: DCVHB79)

Drug Combination Name
Venetoclax APR-246
Indication
Disease Entry Status REF
Myeloid Malignancy Phase 1 [1]
Component Drugs Venetoclax   DM8I94Y APR-246   DMNFADH
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 Venetoclax
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [2]
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 [6]
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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 [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Activity [8]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Folding [10]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [10]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [9]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [10]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Affects Folding [10]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Binding [11]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Affects Response To Substance [12]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of APR-246
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [3]
Bladder cancer 2C94 Phase 1/2 [4]
Gastric adenocarcinoma 2B72 Phase 1/2 [4]
Esophageal cancer 2B70 Phase 1 [3]
Myelodysplastic syndrome 2A37 Phase 1 [3]
Solid tumour/cancer 2A00-2F9Z Preclinical [5]
APR-246 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cellular tumor antigen p53 (TP53) TT7SBF5 P53_HUMAN Stimulator [15]
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APR-246 Interacts with 134 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Response To Substance [13]
RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1) OTLKVFWV RIMC1_HUMAN Affects Expression [13]
Uncharacterized membrane protein C3orf80 (C3ORF80) OTJ16ATH CC080_HUMAN Affects Expression [13]
Splicing regulator ARVCF (ARVCF) OT78DKOU ARVC_HUMAN Affects Expression [13]
DNA fragmentation factor subunit alpha (DFFA) OTFPFMT8 DFFA_HUMAN Affects Expression [13]
F-BAR domain only protein 1 (FCHO1) OTDNDGI9 FCHO1_HUMAN Affects Expression [13]
Chromodomain-helicase-DNA-binding protein 2 (CHD2) OTRKL6YC CHD2_HUMAN Affects Expression [13]
Transcription factor MafG (MAFG) OTBQFUZH MAFG_HUMAN Affects Expression [13]
U4/U6 small nuclear ribonucleoprotein Prp4 (PRPF4) OTK0XRQN PRP4_HUMAN Affects Expression [13]
Eukaryotic translation initiation factor 1b (EIF1B) OTMXLD6F EIF1B_HUMAN Affects Expression [13]
Frizzled-7 (FZD7) OTTK3F6E FZD7_HUMAN Increases Expression [13]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [13]
Leucine-rich repeat and calponin homology domain-containing protein 4 (LRCH4) OTJFA4AV LRCH4_HUMAN Affects Expression [13]
E3 SUMO-protein ligase PIAS2 (PIAS2) OTJLSC3V PIAS2_HUMAN Affects Expression [13]
Transmembrane and coiled-coil domains protein 1 (TMCC1) OTRXDL86 TMCC1_HUMAN Affects Expression [13]
Ferritin light chain (FTL) OTYQA8A6 FRIL_HUMAN Affects Expression [13]
F-box/SPRY domain-containing protein 1 (FBXO45) OTD4D2OP FBSP1_HUMAN Affects Expression [13]
Platelet glycoprotein Ib beta chain (GP1BB) OTD7XNLL GP1BB_HUMAN Increases Expression [13]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [14]
Transcription factor E3 (TFE3) OTM99ZWH TFE3_HUMAN Affects Expression [13]
DnaJ homolog subfamily B member 2 (DNAJB2) OTZHPV5M DNJB2_HUMAN Increases Expression [13]
Microtubule-associated protein 4 (MAP4) OT78YX9J MAP4_HUMAN Increases Expression [13]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Expression [13]
HLA class I histocompatibility antigen, alpha chain F (HLA-F) OT76CM19 HLAF_HUMAN Affects Expression [13]
High affinity cationic amino acid transporter 1 (SLC7A1) OTR2ZVA8 CTR1_HUMAN Affects Expression [13]
ER lumen protein-retaining receptor 2 (KDELR2) OT9QW7Q0 ERD22_HUMAN Affects Expression [13]
Myosin-9 (MYH9) OT94Z706 MYH9_HUMAN Affects Expression [13]
Amiloride-sensitive sodium channel subunit alpha (SCNN1A) OTE2KVZV SCNNA_HUMAN Increases Expression [13]
Interleukin-15 (IL15) OTQSYWQS IL15_HUMAN Affects Expression [13]
Eukaryotic translation initiation factor 1 (EIF1) OTB4GZ0V EIF1_HUMAN Affects Expression [13]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [16]
Neutral amino acid transporter A (SLC1A4) OTVODHAE SATT_HUMAN Affects Expression [13]
Translocon-associated protein subunit alpha (SSR1) OTQ6GDL2 SSRA_HUMAN Affects Expression [13]
Ran GTPase-activating protein 1 (RANGAP1) OTZGD3LJ RAGP1_HUMAN Increases Expression [13]
Protein PRRC2A (PRRC2A) OTBX6FM5 PRC2A_HUMAN Affects Expression [13]
LIM domain kinase 2 (LIMK2) OTRJD7VZ LIMK2_HUMAN Increases Expression [13]
Smoothelin (SMTN) OT4R2TYK SMTN_HUMAN Affects Expression [13]
UV excision repair protein RAD23 homolog A (RAD23A) OTBPAWHX RD23A_HUMAN Affects Expression [13]
UV excision repair protein RAD23 homolog B (RAD23B) OT0PGOG3 RD23B_HUMAN Affects Expression [13]
Eukaryotic translation initiation factor 5 (EIF5) OT79PQUN IF5_HUMAN Increases Expression [13]
Period circadian protein homolog 3 (PER3) OTVKYVJA PER3_HUMAN Affects Expression [13]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Affects Expression [13]
AP-3 complex subunit sigma-2 (AP3S2) OTN8P9OE AP3S2_HUMAN Affects Expression [13]
CD81 antigen (CD81) OTQFXNAZ CD81_HUMAN Increases Expression [13]
Signal peptidase complex subunit 3 (SPCS3) OTAPFSUQ SPCS3_HUMAN Affects Expression [13]
DDB1- and CUL4-associated factor 7 (DCAF7) OT3W5DYL DCAF7_HUMAN Affects Expression [13]
Disks large homolog 4 (DLG4) OTD9E2LU DLG4_HUMAN Affects Expression [13]
Small ribosomal subunit protein uS10m (MRPS10) OTXF7D9J RT10_HUMAN Affects Expression [13]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Increases Activity [17]
Large neutral amino acids transporter small subunit 1 (SLC7A5) OT2WPVXD LAT1_HUMAN Increases Expression [13]
Protein Dr1 (DR1) OTR081M4 NC2B_HUMAN Affects Expression [13]
Transducin-like enhancer protein 4 (TLE4) OT4QEH6T TLE4_HUMAN Affects Expression [13]
Cytoskeleton-associated protein 4 (CKAP4) OTDUC9ME CKAP4_HUMAN Affects Expression [13]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [13]
Golgin subfamily A member 2 (GOLGA2) OT5S9KYM GOGA2_HUMAN Affects Expression [13]
AP-1 complex subunit beta-1 (AP1B1) OTY0K84R AP1B1_HUMAN Affects Expression [13]
HMG domain-containing protein 3 (HMGXB3) OTTZ1AS6 HMGX3_HUMAN Affects Expression [13]
Glutamate receptor ionotropic, NMDA 2A (GRIN2A) OTTP0KN8 NMDE1_HUMAN Affects Expression [13]
Forkhead box protein C1 (FOXC1) OTOWZGYO FOXC1_HUMAN Affects Expression [13]
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D) OTJ5XLVU KCC2D_HUMAN Affects Expression [13]
Protein patched homolog 1 (PTCH1) OTMG07H5 PTC1_HUMAN Decreases Expression [13]
Trophoblast glycoprotein (TPBG) OTU2OTLL TPBG_HUMAN Affects Expression [13]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [13]
HUWE1-associated protein modifying stress responses 1 (HAPSTR1) OTWCI7ZA HAPR1_HUMAN Affects Expression [13]
Astrocytic phosphoprotein PEA-15 (PEA15) OTKCKTSX PEA15_HUMAN Increases Expression [13]
Serine/threonine-protein kinase STK11 (STK11) OT1YZSP3 STK11_HUMAN Increases Expression [13]
Insulin-like growth factor-binding protein 7 (IGFBP7) OT1D416P IBP7_HUMAN Increases Expression [13]
Sister chromatid cohesion protein PDS5 homolog A (PDS5A) OT34P56Z PDS5A_HUMAN Increases Expression [13]
Sprouty-related, EVH1 domain-containing protein 3 (SPRED3) OTPM9N4T SPRE3_HUMAN Affects Expression [13]
Protein FAM161A (FAM161A) OTF5ZRYJ F161A_HUMAN Affects Expression [13]
Transmembrane protein 119 (TMEM119) OT0HFEIC TM119_HUMAN Affects Expression [13]
Sigma intracellular receptor 2 (TMEM97) OTH76ZWK SGMR2_HUMAN Affects Expression [13]
DnaJ homolog subfamily C member 21 (DNAJC21) OT8C14QA DJC21_HUMAN Affects Expression [13]
Meckelin (TMEM67) OTME92T5 MKS3_HUMAN Affects Expression [13]
Spindlin-3 (SPIN3) OT5PTQSH SPIN3_HUMAN Affects Expression [13]
Ceramide-1-phosphate transfer protein (CPTP) OTX3QJIS CPTP_HUMAN Affects Expression [13]
Protein GPR107 (GPR107) OTX5VURU GP107_HUMAN Affects Expression [13]
Cytosolic phospholipase A2 zeta (PLA2G4F) OT8MUO5U PA24F_HUMAN Affects Expression [13]
DENN domain-containing protein 5A (DENND5A) OT0QNNY1 DEN5A_HUMAN Affects Expression [13]
Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (JMJD6) OTILR7E4 JMJD6_HUMAN Affects Expression [13]
DENN domain-containing protein 1B (DENND1B) OT3VCNPE DEN1B_HUMAN Affects Expression [13]
RNA demethylase ALKBH5 (ALKBH5) OT3PW10X ALKB5_HUMAN Affects Expression [13]
Interleukin-34 (IL34) OTZ15VVK IL34_HUMAN Affects Expression [13]
Autophagy-related protein 9A (ATG9A) OTAZWZH7 ATG9A_HUMAN Affects Expression [13]
Cadherin-24 (CDH24) OTNS0BWU CAD24_HUMAN Affects Expression [13]
Centrosomal protein of 57 kDa (CEP57) OTPOHLIX CEP57_HUMAN Affects Expression [13]
Purine nucleoside phosphorylase LACC1 (LACC1) OT4SBHI8 LACC1_HUMAN Affects Expression [13]
Sperm-associated antigen 16 protein (SPAG16) OTIFUPYD SPG16_HUMAN Affects Expression [13]
Protein shisa-5 (SHISA5) OT64VOCE SHSA5_HUMAN Increases Expression [13]
Cytochrome P450 4X1 (CYP4X1) OTMTEUNE CP4X1_HUMAN Affects Expression [13]
Refilin-B (RFLNB) OTI7ZM75 RFLB_HUMAN Affects Expression [13]
Solute carrier family 66 member 3 (SLC66A3) OT8IEN62 S66A3_HUMAN Affects Expression [13]
Procollagen galactosyltransferase 1 (COLGALT1) OTVG0P58 GT251_HUMAN Affects Expression [13]
Reticulophagy regulator 2 (RETREG2) OT5CJTMK RETR2_HUMAN Affects Expression [13]
Hemicentin-2 (HMCN2) OTJK9CGG HMCN2_HUMAN Affects Expression [13]
ATP-dependent RNA helicase DDX54 (DDX54) OTVOJU6G DDX54_HUMAN Affects Expression [13]
Oxoeicosanoid receptor 1 (OXER1) OTQJEAJK OXER1_HUMAN Affects Expression [13]
Probable glutathione peroxidase 8 (GPX8) OTTH80PN GPX8_HUMAN Affects Expression [13]
Ubiquitin carboxyl-terminal hydrolase BAP1 (BAP1) OTS8G0EN BAP1_HUMAN Affects Expression [13]
Run domain Beclin-1-interacting and cysteine-rich domain-containing protein (RUBCN) OTF1UIZC RUBIC_HUMAN Affects Expression [13]
Protein TMEPAI (PMEPA1) OTY8Z9UF PMEPA_HUMAN Affects Expression [13]
Protein shisa-4 (SHISA4) OTJ8H832 SHSA4_HUMAN Affects Expression [13]
OTU domain-containing protein 5 (OTUD5) OTMCR6JM OTUD5_HUMAN Affects Expression [13]
Protein N-terminal glutamine amidohydrolase (NTAQ1) OTY72TPO NTAQ1_HUMAN Affects Expression [13]
RNA-binding protein 41 (RBM41) OTL5WUHE RBM41_HUMAN Affects Expression [13]
Calponin-2 (CNN2) OTH3CSXA CNN2_HUMAN Affects Expression [13]
Retinoic acid receptor responder protein 2 (RARRES2) OT1BJE8K RARR2_HUMAN Affects Expression [13]
A-kinase anchor protein 9 (AKAP9) OT7Z2YRP AKAP9_HUMAN Decreases Expression [13]
Nucleolar protein 10 (NOL10) OTC4R5O7 NOL10_HUMAN Affects Expression [13]
Tubulin-specific chaperone D (TBCD) OTS4JKNQ TBCD_HUMAN Affects Expression [13]
Deoxyhypusine hydroxylase (DOHH) OTDRAT3F DOHH_HUMAN Affects Expression [13]
Spindlin interactor and repressor of chromatin-binding protein (SPINDOC) OTJHLBLA SPNDC_HUMAN Affects Expression [13]
Single-stranded DNA-binding protein 4 (SSBP4) OTTK1ZHQ SSBP4_HUMAN Affects Expression [13]
Caspase recruitment domain-containing protein 10 (CARD10) OT2RPM4I CAR10_HUMAN Increases Expression [13]
E3 ubiquitin-protein ligase RNF26 (RNF26) OTPXA60S RNF26_HUMAN Affects Expression [13]
Tripartite motif-containing protein 5 (TRIM5) OTMZH7EJ TRIM5_HUMAN Affects Expression [13]
Talin rod domain-containing protein 1 (TLNRD1) OTNOLROI TLRN1_HUMAN Affects Expression [13]
A disintegrin and metalloproteinase with thrombospondin motifs 10 (ADAMTS10) OTNJ9VSU ATS10_HUMAN Affects Expression [13]
Pleckstrin homology domain-containing family A member 4 (PLEKHA4) OTNOCQTF PKHA4_HUMAN Affects Expression [13]
Protein bicaudal C homolog 1 (BICC1) OTYRKIJ1 BICC1_HUMAN Affects Expression [13]
Vasculin-like protein 1 (GPBP1L1) OTSSORWC GPBL1_HUMAN Affects Expression [13]
RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72) OTW9L6S4 SSU72_HUMAN Affects Expression [13]
Anillin (ANLN) OTXJY54C ANLN_HUMAN Affects Expression [13]
Midasin (MDN1) OTNBSPTW MDN1_HUMAN Affects Expression [13]
Protein eva-1 homolog B (EVA1B) OTDNAKQD EVA1B_HUMAN Affects Expression [13]
Protein AATF (AATF) OT1QOKLD AATF_HUMAN Increases Expression [13]
Short coiled-coil protein (SCOC) OTPJ3RQ4 SCOC_HUMAN Affects Expression [13]
F-box/LRR-repeat protein 4 (FBXL4) OTZECCIQ FBXL4_HUMAN Affects Expression [13]
Histone chaperone ASF1A (ASF1A) OT4S44GP ASF1A_HUMAN Affects Expression [13]
Nischarin (NISCH) OTTMT8UD NISCH_HUMAN Affects Expression [13]
Tudor and KH domain-containing protein (TDRKH) OTV21BN1 TDRKH_HUMAN Affects Expression [13]
Malignant fibrous histiocytoma-amplified sequence 1 (MFHAS1) OTS922CJ MFHA1_HUMAN Affects Expression [13]
E3 ubiquitin-protein ligase RNF115 (RNF115) OT35B6L5 RN115_HUMAN Affects Expression [13]
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⏷ Show the Full List of 134 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Recurrent Mantle Cell Lymphoma DCGU65J N. A. Phase 2 [18]
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References

1 ClinicalTrials.gov (NCT04214860) APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 ClinicalTrials.gov (NCT04383938) Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies. U.S. National Institutes of Health.
5 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030246)
6 Venclexta FDA label
7 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.
8 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.
9 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.
10 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.
11 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.
12 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.
13 Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
14 PARP-1 inhibitors sensitize HNSCC cells to APR-246 by inactivation of thioredoxin reductase 1 (TrxR1) and promotion of ROS accumulation. Oncotarget. 2017 Sep 26;9(2):1885-1897. doi: 10.18632/oncotarget.21277. eCollection 2018 Jan 5.
15 APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis. 2013 Oct 24;4:e881.
16 Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1 and Mutant p53 and Can Be Overcome by Induction of Oxidative Stress. Cancers (Basel). 2018 Apr 21;10(4):126. doi: 10.3390/cancers10040126.
17 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
18 ClinicalTrials.gov (NCT04990778) Venetoclax and Eprenetapopt for the Treatment of Relapsed of Refractory Mantle Cell Lymphoma