Details of the Drug Combination

General Information of Drug Combination (ID: DCGU65J)

• Drug Combination Name: Venetoclax + APR-246
• Indication: Recurrent Mantle Cell Lymphoma; Status: Phase 2 [1]
• Component Drugs:
  Venetoclax (DM8I94Y): Small molecular drug
  APR-246 (DMNFADH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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]

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]

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]

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]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Myeloid Malignancy	DCVHB79	N. A.	Phase 1	[18]

References

• [1] ClinicalTrials.gov (NCT04990778) Venetoclax and Eprenetapopt for the Treatment of Relapsed of Refractory Mantle Cell Lymphoma
• [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 (NCT04214860) APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies