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DRUG CLASS:

p53 reactivator

1d
A Study to Investigate the Effects of Acid Reducing Agents on Pharmacokinetics of PC14586 in Healthy Participants (clinicaltrials.gov)
P1, N=28, Completed, PMV Pharmaceuticals, Inc | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024
Trial completion • Trial completion date
|
rezatapopt (PC14586)
1d
Trial completion
|
itraconazole • rezatapopt (PC14586)
2ms
New P1 trial • Combination therapy
|
Venclexta (venetoclax) • azacitidine • rezatapopt (PC14586)
3ms
Astilbin Induces Apoptosis in Oral Squamous Cell Carcinoma through p53 Reactivation and Mdm-2 Inhibition. (PubMed, Dokl Biochem Biophys)
This was followed by the induction of mitochondrial intrinsic apoptosis via the activation of caspases 9 and 3, cleavage of PARP, and the suppression of pro-apoptotic Bid. Astilbin-induced p53-mediated apoptosis in OSCC cells as herbal medicinal ingredients.
Journal • PARP Biomarker
|
CASP9 (Caspase 9)
|
RITA
3ms
MiR-34b promotes oxidative stress and induces cellular senescence through TWIST1 in human cervical cancer. (PubMed, Transl Oncol)
MiR-34b promotes cellular senescence and oxidative stress by targeting TWIST1, a known oncogene and EMT regulator. This study delved into the mechanism of miR-34b-mediated tumor suppression and provided novel insights for development of miR-34b based therapeutics for cervical cancer.
Journal
|
TWIST1 (Twist Family BHLH Transcription Factor 1) • MIR34B (MicroRNA 34b)
|
RITA
5ms
APR-246 as a radiosensitization strategy for mutant p53 cancers treated with alpha-particles-based radiotherapy. (PubMed, Cell Death Dis)
Combining alpha-particles-based RT with p53 restoration via APR-246 triggered cell death, resulting in improved therapeutic outcomes. Further preclinical and clinical studies are needed to provide a promising approach for improving treatment outcomes in patients with mutant p53 tumors.
Journal • IO biomarker
|
TP53 (Tumor protein P53)
|
eprenetapopt (APR-246)
5ms
Structural basis of p53 inactivation by cavity-creating cancer mutations and its implications for the development of mutant p53 reactivators. (PubMed, Cell Death Dis)
Differential stabilization of the mutants upon treatment with the anticancer agent arsenic trioxide and stibogluconate revealed an interesting proximity effect...Intriguingly, our structural studies suggest a pronounced plasticity of the mutation-induced pocket in the frequently occurring Y163C mutant, which may be exploited for the development of small-molecule stabilizers. We point out general principles for reactivating thermolabile cancer mutants and highlight special cases where mutant-specific drugs are needed for the pharmacological rescue of p53 function in tumors.
Journal
|
TP53 (Tumor protein P53)
|
arsenic trioxide
6ms
Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis). (PubMed, Cell Death Dis)
Taken together, ARID1A loss significantly heightens sensitivity to RITA in CRC, revealing a novel synthetic lethal interaction between ARID1A and RITA. These findings present a promising therapeutic approach for colorectal cancer characterized by ARID1A loss-of-function mutations.
Journal
|
ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
RITA
6ms
Foundation Medicine and PMV Pharma Announce Collaboration to Develop Companion Diagnostic for Rezatapopt, a First-In-Class, Investigational, Selective p53 Y220C Reactivator (GlobeNewswire)
"Foundation Medicine, Inc. and PMV Pharmaceuticals, Inc...announced a partnership to develop Foundation Medicine’s tissue-based comprehensive genomic profiling test, FoundationOneCDx, as a companion diagnostic for PMV Pharma’s rezatapopt, a first-in-class, investigational therapy for patients with locally advanced or metastatic solid tumors that have a TP53 Y220C mutation."
Licensing / partnership
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FoundationOne® CDx
|
rezatapopt (PC14586)
6ms
Mutant p53 reactivators protect breast cancer cells from ferroptosis. (PubMed, Cell Biochem Funct)
One of these p53 reactivator molecules, NSC 59984, reduced expression of GPX4, which is unlikely to explain its ability to reduce sensitivity to ferroptosis. We suggest that these p53 reactivators function via an unknown, p53-independent manner to suppress ferroptosis.
Journal
|
TP53 (Tumor protein P53) • GPX4 (Glutathione Peroxidase 4)
|
NSC59984
6ms
TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates. (PubMed, Am Soc Clin Oncol Educ Book)
The most heavily investigated and targeted agent for patients with TP53-mutant MDS and AML has been APR-246 (eprenetapopt) a p53 reactivator, in combination with azacitidine, but also in triplets with venetoclax...Other agents, like magrolimab (anti-CD47 antibody), failed to demonstrate improved activity in TP53-mutant MDS and AML...Delivering prognostic information in a dismal disease like TP53-mutated MDS and AML is particularly challenging. The physician should balance hope and realism, describing the trajectory of possible treatments and at the same time indicating the poor outcome, together with promoting adaptive coping in patients and elaborating on the nature of the disease.
Review • Journal
|
TP53 (Tumor protein P53) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
TP53 mutation
|
Venclexta (venetoclax) • azacitidine • eprenetapopt (APR-246) • magrolimab (ONO-7913)
6ms
Mutant p53 reactivation restricts the protumorigenic consequences of wild type p53 loss of heterozygosity in Li-Fraumeni syndrome patient-derived fibroblasts. (PubMed, Cell Death Differ)
Furthermore, prolonged treatment with pCAP-250 significantly reduces DNA damage and restores long-term genomic stability. pCAPs may thus be contemplated as a potential preventive treatment to prevent or delay early onset cancer in carriers of mutant p53.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type • TP53 R248Q
7ms
Metabolic fingerprinting by nuclear magnetic resonance of hepatocellular carcinoma cells during p53 reactivation-induced senescence. (PubMed, NMR Biomed)
MRS studies with the cell perfusion system revealed elevated creatine levels in senescent cells on Day 4, confirming the 1H-NMR results. These senescence-associated changes in metabolism and ECM degradation strongly impact growth and redox metabolism and reveal potential MRS signals for detecting senescent cancer cells in vivo.
Journal
|
TP53 (Tumor protein P53)
|
TP53 expression
9ms
p53-dependent HIF-1α /autophagy mediated glycolysis to support Cr(VI)-induced cell growth and cell migration. (PubMed, Ecotoxicol Environ Saf)
RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis.
Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • ATG4B (Autophagy Related 4B Cysteine Peptidase)
|
HIF1A expression
|
RITA
11ms
TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment. (PubMed, Prostate)
DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.
Journal • Metastases
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type • TP53 R175H
|
eprenetapopt (APR-246)
12ms
Enhanced TP53 reactivation disrupts MYC transcriptional program and overcomes venetoclax resistance in acute myeloid leukemias. (PubMed, Sci Adv)
The triple inhibition of MDM2, XPO1, and BCL2 was highly effective against venetoclax-resistant AML in vivo. Our results propose a novel, highly translatable therapeutic approach leveraging p53 reactivation to overcome nongenetic, stress-adapted venetoclax resistance.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2)
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MYC expression
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Venclexta (venetoclax)
12ms
Altering relative metal-binding affinities in multifunctional Metallochaperones for mutant p53 reactivation. (PubMed, J Inorg Biochem)
High levels of ROS can result in off-target effects and general toxicity, and thus, careful tuning of ligand Zn affinity, in comparison to the affinity for other endogenous metals, is important for selective mutant p53 targeting. In this work we show that by using carboxylate donors in place of pyridine we can change the relative Zn/Cu binding ability in a series of ligands, and we investigate the impact of donor group changes on metallochaperone activity and overall cytotoxicity in two mutant p53 cancer cell lines (NUGC3 and SKGT2).
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation
12ms
Deep learning untangles the resistance mechanism of p53 reactivator in lung cancer cells. (PubMed, iScience)
We further discovered the positive feedback loop between THBS1 and the TGF-β pathway as the main source of resistance. This study enhances our understanding of p53 regulation and offers insights into overcoming drug resistance.
Journal
|
TGFB1 (Transforming Growth Factor Beta 1)
12ms
Establishment of ganglioside GD2-expressing extranodal NK/T cell lymphoma cell line with scRNA-seq analysis. (PubMed, Exp Hematol)
The molecular target agents eprenetapopt, tazemetostat, and vorinostat efficiently induced apoptosis in ENKL-J1 cells in vitro. Furthermore, GD2-directed chimeric antigen receptor T cells showed cytotoxicity against ENKL-J1 cells in vivo. These findings not only contribute to understanding the molecular and genomic characteristics of ENKL; they also suggest new treatment options for patients with advanced or relapsed ENKL.
Preclinical • Journal • IO biomarker
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PD-L1 (Programmed death ligand 1) • BCL2 (B-cell CLL/lymphoma 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • BCL2L1 (BCL2-like 1) • ABCC1 (ATP Binding Cassette Subfamily C Member 1) • HDAC2 (Histone deacetylase 2) • FOXO3 (Forkhead box O3) • ATG5 (Autophagy Related 5) • DDX3X (DEAD-Box Helicase 3 X-Linked)
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Zolinza (vorinostat) • eprenetapopt (APR-246) • Tazverik (tazemetostat)
12ms
Targeting mutant-p53 for cancer treatment: Are we there yet? (PubMed, Curr Mol Pharmacol)
The progress of developing a cancer treatment that may successfully and efficiently target mutant p53 is on the verge of development. Mutant p53 proteins not only initiate oncogenesis but also cause resistance in cancer cells to certain chemo or radiotherapies, further endorse cancer cell survival and promote migration as well as metastasis of cancerous cells. With this regard, many mutant p53 inhibitors have been developed, some of which are currently being evaluated at the pre-clinical level and have been identified and discussed. To date, APR-246 is the most prominent one that has progressed to the Phase III clinical trial.
Journal
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TP53 (Tumor protein P53)
|
TP53 mutation
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eprenetapopt (APR-246)
12ms
Mutant p53 gain-of-function stimulates canonical Wnt signaling via PI3K/AKT pathway in colon cancer. (PubMed, J Cell Commun Signal)
We also found that while wt-p53 expression contributes to 5-FU sensitivity in colon cancer cells, the RITA p53 reactivating molecule counteracted the resistance against 5-FU in cells expressing mut-p53. Our results indicate that mut-p53 GOF acts as a positive regulator of canonical Wnt signaling and participates in the induction of resistance to 5-FU in colon cancer cells.
Journal
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TP53 (Tumor protein P53)
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TP53 mutation • TP53 wild-type • TP53 overexpression
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5-fluorouracil • RITA
1year
Selective Targeting of TP53-Y220C Mutant AML By PC14586 Results in TP53 Wild-Type Conformation and Synergistical Apoptosis Induction By Concomitant Inhibition of Xpo-1, MDM2, or Bcl-2 (ASH 2023)
Mechanism-based combinations with XPO-1, MDM2, and Bcl-2 inhibitors induce massive apoptosis. PC14586 is presently in early clinical trials.
PARP Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD34 (CD34 molecule) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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TP53 mutation • TP53 wild-type • TP53 R175H • TP53 Y220C
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rezatapopt (PC14586)
1year
TP53 Y220C Mutations in Patients with Myeloid Malignancies (ASH 2023)
A novel Y220C-targeted small molecule (PC14586) has shown preliminary efficacy and safety in patients with solid tumors (Dumbrava, E., ASCO 2022)... TP53 Y220C mutations are present in malignant blood disorders and are particularly more common in myelodysplastic syndromes and acute myeloid leukemia, with associated poor outcomes. Novel targeted therapies for this TP53 variant (Y220C) would be of interest for this patient population.
Clinical
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TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
|
TP53 mutation • DNMT3A mutation • TET2 mutation • TP53 Y220C
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rezatapopt (PC14586)
1year
APR-246 increases tumor antigenicity independent of p53. (PubMed, Life Sci Alliance)
We propose that the immunogenic effect of MQ can be linked to its thiol-reactive alkylating ability as we observed similar immunogenic effects with the broad-spectrum cysteine-reactive compound, iodoacetamide. Our results thus indicate that combination of APR-246 with immunomodulatory agents may elicit effective antitumor immune response irrespective of the tumor's p53 mutation status.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • TLR4 (Toll Like Receptor 4) • CD40 (CD40 Molecule)
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TP53 mutation
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eprenetapopt (APR-246)
1year
Integrative analyses reveal outcome-associated and targetable molecular partnerships between TP53, BRD4, TNFRSF10B, and CDKN1A in diffuse large B-cell lymphoma. (PubMed, Ann Hematol)
Promisingly, in vitro MDM2 inhibition with Idasnutlin and TP53 reactivation via Eprenetapopt was able to renew TNFRSF10B protein expression. Additionally, applying the BRD4-degrading PROTAC ARV-825 and the CDK4/6 inhibitor Abemaciclib as single-agents and in synergistic combination significantly reduced TP53-altered DLBCL cell line viability. Our analysis presents key associations within a genomic network of actionable targets capable of providing clarity within the evolving precision CAR-T treatment landscape.
Licensing / partnership • Journal • IO biomarker
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TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • BRD4 (Bromodomain Containing 4) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
|
TP53 expression
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Verzenio (abemaciclib) • eprenetapopt (APR-246) • ARV-825
1year
The Impact of TP53 Mutations and Use of the TP53-Mutation-Reactivating Agent APR-246 on Metastatic Castrate-Sensitive Prostate Cancer. (PubMed, Int J Radiat Oncol Biol Phys)
DN TP53 mutations were associated with poorer survival outcomes for mCSPC patients. DN TP53 mutations also promoted prostate cancer pro-metastatic behaviors in vitro, which was effectively counteracted by APR-246, making it a promising treatment option that should be explored further in early-phase clinical studies.
Journal • Metastases
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type • TP53 R175H
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eprenetapopt (APR-246)
1year
TP53-mutated acute myeloid leukemia and myelodysplastic syndrome: biology, treatment challenges, and upcoming approaches. (PubMed, Ann Hematol)
The triple combination of azacitidine and venetoclax with either magrolimab or eprenetapopt have demonstrated safety in early trials, with phase III trials currently underway, and promising interim clinical results. This review compiles background on TP53 biology, available and emerging therapies along with their mechanisms of action for the TP53m disease entity, current treatment challenges, and recently published data and status of ongoing clinical trials for TP53m AML/MDS.
Review • Journal • IO biomarker
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TP53 (Tumor protein P53)
|
TP53 mutation
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Venclexta (venetoclax) • azacitidine • eprenetapopt (APR-246) • magrolimab (ONO-7913)
1year
Clinical • P1/2 data • Late-breaking abstract • Metastases
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TP53 (Tumor protein P53)
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TP53 mutation • TP53 Y220C
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rezatapopt (PC14586)
1year
The p53 reactivator PRIMA-1 synergises with 5-fluorouracil to induce apoptosis in pancreatic cancer cells. (PubMed, Invest New Drugs)
The synergism of the combination was associated with significant apoptosis induction through p53-dependent and p53-independent pathways. Preclinical confirmation of these data in in vivo models is highly recommended.
Journal
|
TP73 (Tumor Protein P73)
|
TP53 mutation • TP53 wild-type
|
5-fluorouracil • eprenetapopt (APR-246)
1year
The Impact of TP53 Mutations and Use of the TP53-Mutation-Reactivating Agent APR-246 on Metastatic Castrate-Sensitive Prostate Cancer (ASTRO 2023)
DN TP53 mutations were associated with poorer survival outcomes for mCSPC patients. DN TP53 mutations also promoted prostate cancer pro-metastatic behaviors in vitro , which was effectively counteracted by APR-246, making it a promising treatment option that should be explored further in early-phase clinical studies.
Metastases
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type • TP53 R175H
|
eprenetapopt (APR-246)
1year
Nucleolar phosphoprotein modifications as a marker of apoptosis induced by RITA treatment. (PubMed, Biochim Biophys Acta Mol Cell Res)
Simultaneously, inverse changes occurred at Serine S4 of the NPM. These new findings of RITA mechanism of action could establish the NPM pT199/pS4 ratio as a marker for suitability of RITA treatment of AML cells.
Journal
|
NPM1 (Nucleophosmin 1) • NCL (Nucleolin)
|
TP53 mutation • TP53 wild-type
|
RITA
over1year
APR-246 in Combination With Acalabrutinib or Venetoclax Based Therapy in Subjects With R/R Non Hodgkin Lymphomas (NHL) (clinicaltrials.gov)
P1/2, N=1, Terminated, Aprea Therapeutics | N=100 --> 1 | Suspended --> Terminated; Sponsor decision
Enrollment change • Trial termination • Combination therapy
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
Venclexta (venetoclax) • Rituxan (rituximab) • Calquence (acalabrutinib) • eprenetapopt (APR-246)
over1year
APR-246 enhances colorectal cancer sensitivity to radiotherapy. (PubMed, Mol Cancer Ther)
APR-246 mediated radio-sensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in rectal cancer patients.
Journal
|
TP53 mutation • TP53 wild-type
|
eprenetapopt (APR-246)
over1year
RITA selectively inhibits proliferation of BAP1-deficient cutaneous melanoma cells in vitro (PubMed, Nan Fang Yi Ke Da Xue Xue Bao)
Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Preclinical • Journal
|
BAP1 (BRCA1 Associated Protein 1)
|
BAP1 mutation • BAP1 deletion • TP53 expression
|
RITA
over1year
Restoring p53 activity as an approach to target aggressive stem-like childhood sarcomas (EACR 2023)
Drugs that target the p53 pathway (mutant p53 re-activator PRIMA-1MET, dual MDM2/MDMX inhibitor RO-5963, and LEM3, a new molecule targeting interactions of MDM2/p53 family proteins) markedly inhibited viability of tumorigenic Ewing's sarcoma cells, demonstrating their increased vulnerability to restoring the p53 activity compared with nontumorigenic cells. Treatment with RO-5963 and LEM3 in tumorigenic cells stabilized p53 and induced apoptosis in a dose-dependent manner.ConclusionSOX2 expression and the p53 pathway deregulation are associated with sarcoma stemness. Our results indicate that enhanced p53 activity might effectively target aggressive stem-like childhood sarcomas, therefore showing promising clinical potential for p53 pathway re-activation in sarcoma therapy.
Clinical
|
SOX2 • POU5F1 (POU Class 5 Homeobox 1) • NANOG (Nanog Homeobox)
|
TP53 mutation • TP53 expression • SOX2 expression
|
eprenetapopt (APR-246)
over1year
In silico and in vitro investigation of dual targeting Prima-1 as precision therapeutic against lungs cancer. (PubMed, J Biomol Struct Dyn)
A significant decrease in intracellular ROS was observed and resulted in disruption of mitochondrial transmembrane potential. This study uncovers the underlying mechanism of Prima-1 and could be helpful to design further leads against lung cancers.Communicated by Ramaswamy H. Sarma.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53)
|
TP53 expression
|
eprenetapopt (APR-246)
over1year
Degradation of MYC by the mutant p53 reactivator drug, COTI-2 in breast cancer cells. (PubMed, Invest New Drugs)
Proteasome-mediated degradation was determined using the proteasome, inhibitor MG-132, while MYC half-life was measured using pulse chase experiments in the presence of cycloheximide. Co-treatment with COTI-2 and the MYC inhibitor, MYCi975 resulted in synergistic growth inhibition in all 4 mutant p53 cell lines investigated. The dual ability of COTI-2 to reactivate mutant p53 and degrade MYC should enable this compound to have broad application as an anticancer drug.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
COTI-2 • MG132 • MYCi975
over1year
Therapeutic Targets in Myelodysplastic Neoplasms: Beyond Hypomethylating Agents. (PubMed, Curr Hematol Malig Rep)
Pevonedistat (NEDD-8 inhibitor) and APR-246 (TP53 reactivator) both did not meet trial endpoints. Due to intolerance, primary, and secondary resistance to HMA, there is a large unmet need to develop new safe and effective therapies for patients with MDS. In this review, we focus on the current management strategies and novel therapies in development for treatment of high-risk MDS.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
|
eprenetapopt (APR-246) • pevonedistat (MLN4924)
over1year
Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer. (PubMed, J Cancer Res Clin Oncol)
This discovery revealed the specific mechanism of ferroptosis induced by apatinib combined with olaparib in p53 wild-type ovarian cancer cells and provided a theoretical basis for the clinical combined use of apatinib and olaparib in p53 wild-type ovarian cancer patients.
Journal • BRCA Biomarker • PARP Biomarker
|
BRCA (Breast cancer early onset) • GPX4 (Glutathione Peroxidase 4)
|
TP53 mutation • TP53 wild-type • BRCA wild-type • GPX4 expression
|
Lynparza (olaparib) • AiTan (rivoceranib) • sirolimus • RITA • Skyclarys (omaveloxolone)
over1year
The impact of TP53 mutations and use of the TP53-mutation-reactivating agent APR-246 on metastatic castrate-sensitive prostate cancer. (ASCO 2023)
DN TP53 mutations were associated with poorer survival outcomes for mCSPC patients. DN TP53 mutations also promoted prostate cancer pro-metastatic behaviors in vitro, which was effectively counteracted by APR-246, making it a promising treatment option that should be explored further in early-phase clinical studies.
Metastases
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type • TP53 R175H
|
eprenetapopt (APR-246)
over1year
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation (PYNNACLE) (clinicaltrials.gov)
P1/2, N=181, Recruiting, PMV Pharmaceuticals, Inc | Trial completion date: Dec 2025 --> Jul 2026 | Trial primary completion date: Nov 2024 --> Mar 2026
Trial completion date • Trial primary completion date • Metastases
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 Y220C
|
Keytruda (pembrolizumab) • rezatapopt (PC14586)
over1year
The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells. (PubMed, Cell Death Differ)
The sensitivity of non-transformed cells to APR-246 also depended on the cell type. These findings reveal that the clinical testing of APR-246 should not be limited to cancers expressing mutant TP53 but expanded to cancers that express wt TP53 or are TP53-deficient.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type • MYC expression • TP53 expression
|
eprenetapopt (APR-246)