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MedKoo Cat#: 205945 | Name: Eprenetapopt
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Eprenetapop, also known as PRIMA-1MET and APR-246 is p53 activator. Eprenetapopt is a methylated derivative and structural analog of PRIMA-1 (p53 re-activation and induction of massive apoptosis), with potential antineoplastic activity. Upon administration, eprenetapopt covalently modifies the core domain of mutated forms of cellular tumor antigen p53 (p53) through the alkylation of thiol groups. These modifications restore both the wild-type conformation and function to mutant p53, which reconstitutes endogenous p53 activity, leading to cell cycle arrest and apoptosis in tumor cells. This agent may work synergistically with other antineoplastic agents.

Chemical Structure

Eprenetapopt
Eprenetapopt
CAS#5291-32-7

Theoretical Analysis

MedKoo Cat#: 205945

Name: Eprenetapopt

CAS#: 5291-32-7

Chemical Formula: C10H17NO3

Exact Mass: 199.1208

Molecular Weight: 199.25

Elemental Analysis: C, 60.28; H, 8.60; N, 7.03; O, 24.09

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,650.00 Ready to ship
1g USD 2,950.00 Ready to ship
2g USD 5,250.00 Ready to ship
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Related CAS #
No Data
Synonym
APR246; APR-246; APR 246. PRIMA-1MET; Eprenetapopt;
IUPAC/Chemical Name
2-(hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one
InChi Key
BGBNULCRKBVAKL-UHFFFAOYSA-N
InChi Code
InChI=1S/C10H17NO3/c1-14-7-10(6-12)9(13)8-2-4-11(10)5-3-8/h8,12H,2-7H2,1H3
SMILES Code
O=C1C(COC)(CO)N2CCC1CC2
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, DMF, PBS, and EtOH
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
APR-246 is a first-in-class, small molecule that restores wild-type p53 functions in TP53-mutant cells.
In vitro activity:
Since APR-246 depletes GSH (glutathione) and system xC− blockade leads to cystine starvation, which in turn impairs GSH synthesis, it was examined whether their therapeutic combination would synergistically target mut-p53 cancer cells. APR-246 was applied to esophageal cell lines following SLC7A11 knockdown. Inhibiting SLC7A11 expression significantly enhanced the efficacy of APR-246, particularly against cancer cells with mut-p53 accumulation (Fig. 7a), resulting in synergistic induction of ROS and apoptosis (Fig. 7b,c; Supplementary Fig. 7a). Mechanistically, system xC− blockade in conjunction with APR-246 synergistically depleted intracellular GSH, resulting in mitochondrial ROS (reactive oxygen species) accumulation, lipid peroxidation and ultimately apoptotic cell death (Fig. 7h–k; Supplementary Fig. 7e–h). Reference: Nat Commun. 2017 Mar 28;8:14844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379068/
In vivo activity:
In FLO-1 xenografts, SLC7A11 knockdown significantly enhanced the anti-tumour activity of APR-246 (Fig. 8b,c; Supplementary Fig. 8k), leading to synergistic reduction of intratumoral GSH levels and improved animal survival (Fig. 8d,e). Consistent with this, the combination of SAS (sulfasalazine) with APR-246 at tolerated doses (Supplementary Fig. 8l,m) also conferred greater anti-tumour activity than single agents alone (Fig. 8f). Importantly, these findings were reproduced in a PDX model of mut-p53 high-expressing oesophageal cancer (Fig. 8g–i; Supplementary Fig. 8n–o). Analysis of these tumours revealed markedly reduced proliferation and increased apoptosis (Fig. 8j). These results demonstrate the therapeutic potential of combining system xC− inhibitors with APR-246 to synergistically target cancer cells with mut-p53 accumulation. Reference: Nat Commun. 2017 Mar 28;8:14844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379068/
Solvent mg/mL mM
Solubility
DMSO 53.3 267.65
Water 45.0 225.85
Ethanol 32.5 163.11
DMF 30.0 150.56
PBS (pH 7.2) 5.0 25.09
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 199.25 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Liu DS, Duong CP, Haupt S, Montgomery KG, House CM, Azar WJ, Pearson HB, Fisher OM, Read M, Guerra GR, Haupt Y, Cullinane C, Wiman KG, Abrahmsen L, Phillips WA, Clemons NJ. Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation. Nat Commun. 2017 Mar 28;8:14844. doi: 10.1038/ncomms14844. PMID: 28348409; PMCID: PMC5379068.
In vitro protocol:
1. Liu DS, Duong CP, Haupt S, Montgomery KG, House CM, Azar WJ, Pearson HB, Fisher OM, Read M, Guerra GR, Haupt Y, Cullinane C, Wiman KG, Abrahmsen L, Phillips WA, Clemons NJ. Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation. Nat Commun. 2017 Mar 28;8:14844. doi: 10.1038/ncomms14844. PMID: 28348409; PMCID: PMC5379068.
In vivo protocol:
1. Liu DS, Duong CP, Haupt S, Montgomery KG, House CM, Azar WJ, Pearson HB, Fisher OM, Read M, Guerra GR, Haupt Y, Cullinane C, Wiman KG, Abrahmsen L, Phillips WA, Clemons NJ. Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation. Nat Commun. 2017 Mar 28;8:14844. doi: 10.1038/ncomms14844. PMID: 28348409; PMCID: PMC5379068.
1: Michaeli O, Luz I, Vatarescu M, Manko T, Weizman N, Korotinsky Y, Tsitrina A, Braiman A, Arazi L, Cooks T. APR-246 as a radiosensitization strategy for mutant p53 cancers treated with alpha-particles-based radiotherapy. Cell Death Dis. 2024 Jun 18;15(6):426. doi: 10.1038/s41419-024-06830-3. PMID: 38890278; PMCID: PMC11189442. 2: Strandgren C, Wiman KG. Therapeutic targeting of TP53 nonsense mutations in cancer. Ups J Med Sci. 2024 May 27;129. doi: 10.48101/ujms.v129.10719. PMID: 38863730; PMCID: PMC11165251. 3: Santini V, Stahl M, Sallman DA. TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates. Am Soc Clin Oncol Educ Book. 2024 Jun;44(3):e432650. doi: 10.1200/EDBK_432650. PMID: 38768424. 4: Zhang L-B, Qiu T-T, Qiu X-G, Yang W-W-J, Ye X-Y, Meng C. Transcriptomic and metabolomic analysis unveils a negative effect of glutathione metabolism on laccase activity in Cerrena unicolor 87613. Microbiol Spectr. 2024 Feb 6;12(2):e0340523. doi: 10.1128/spectrum.03405-23. Epub 2024 Jan 17. PMID: 38230929; PMCID: PMC10846260. 5: Palomar-Siles M, Yurevych V, Bykov VJN, Wiman KG. Pharmacological induction of translational readthrough of nonsense mutations in the retinoblastoma (RB1) gene. PLoS One. 2023 Nov 2;18(11):e0292468. doi: 10.1371/journal.pone.0292468. PMID: 37917619; PMCID: PMC10621805. 6: Michels J, Venkatesh D, Liu C, Budhu S, Zhong H, George MM, Thach D, Yao ZK, Ouerfelli O, Liu H, Stockwell BR, Campesato LF, Zamarin D, Zappasodi R, Wolchok JD, Merghoub T. APR-246 increases tumor antigenicity independent of p53. Life Sci Alliance. 2023 Oct 27;7(1):e202301999. doi: 10.26508/lsa.202301999. PMID: 37891002; PMCID: PMC10610029. 7: Hoang T, Sutera P, Nguyen T, Chang J, Jagtap S, Song Y, Shetty AC, Chowdhury DD, Chan A, Carrieri FA, Hathout L, Ennis R, Jabbour SK, Parikh R, Molitoris J, Song DY, DeWeese T, Marchionni L, Ren L, Sawant A, Simone N, Lafargue A, Van Der Eecken K, Bunz F, Ost P, Tran PT, Deek MP. TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment. Prostate. 2024 Jan;84(1):87-99. doi: 10.1002/pros.24629. Epub 2023 Oct 9. PMID: 37812042. 8: Lim DV, Woo WH, Lim JX, Loh XY, Soh HT, Lim SYA, Lee ZY, Yow HY, Hamzah SB, Sellappans R, Foo JB. Targeting Mutant-p53 for Cancer Treatment: Are We There Yet? Curr Mol Pharmacol. 2024;17(1):e140923221042. doi: 10.2174/1874467217666230914090621. PMID: 37711005. 9: Brahme A. TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology. Cancers (Basel). 2023 Aug 27;15(17):4286. doi: 10.3390/cancers15174286. PMID: 37686565; PMCID: PMC10487030. 10: Heldin A, Cancer M, Palomar-Siles M, Öhlin S, Zhang M, Sun-Zhang A, Mariani A, Liu J, Bykov VJN, Wiman KG. Novel compounds that synergize with aminoglycoside G418 or eRF3 degraders for translational readthrough of nonsense mutant TP53 and PTEN. RNA Biol. 2023 Jan;20(1):368-383. doi: 10.1080/15476286.2023.2222250. PMID: 37339263; PMCID: PMC10283442. 11: Xie X, Fan C, Luo B, Zhang J, Jensen LD, Burman J, Jönsson C, Ljusberg A, Larsson P, Zhao Z, Sun XF. APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy. Mol Cancer Ther. 2023 Aug 1;22(8):947-961. doi: 10.1158/1535-7163.MCT-22-0275. PMID: 37216282; PMCID: PMC10390889. 12: Pophali P, Desai SR, Shastri A. Therapeutic Targets in Myelodysplastic Neoplasms: Beyond Hypomethylating Agents. Curr Hematol Malig Rep. 2023 Jun;18(3):56-67. doi: 10.1007/s11899-023-00693-9. Epub 2023 Apr 13. PMID: 37052811. 13: Garcia-Manero G, Goldberg AD, Winer ES, Altman JK, Fathi AT, Odenike O, Roboz GJ, Sweet K, Miller C, Wennborg A, Hickman DK, Kanagal-Shamanna R, Kantarjian H, Lancet J, Komrokji R, Attar EC, Sallman DA. Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. Lancet Haematol. 2023 Apr;10(4):e272-e283. doi: 10.1016/S2352-3026(22)00403-3. PMID: 36990622. 14: Nagourney AJ, Gipoor JB, Evans SS, D'Amora P, Duesberg MS, Bernard PJ, Francisco F, Nagourney RA. Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants. Genes (Basel). 2023 Mar 19;14(3):747. doi: 10.3390/genes14030747. PMID: 36981018; PMCID: PMC10048363. 15: Wang Z, Hu H, Heitink L, Rogers K, You Y, Tan T, Suen CLW, Garnham A, Chen H, Lieschke E, Diepstraten ST, Chang C, Chen T, Moujalled D, Sutherland K, Lessene G, Sieber OM, Visvader J, Kelly GL, Strasser A. Correction to: The anti- cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells. Cell Death Differ. 2023 Apr;30(4):1096. doi: 10.1038/s41418-023-01137-w. Erratum for: Cell Death Differ. 2023 Apr;30(4):1033-1046. doi: 10.1038/s41418-023-01122-3. PMID: 36828917; PMCID: PMC10070347. 16: Wang Z, Hu H, Heitink L, Rogers K, You Y, Tan T, Suen CLW, Garnham A, Chen H, Lieschke E, Diepstraten ST, Chang C, Chen T, Moujalled D, Sutherland K, Lessene G, Sieber OM, Visvader J, Kelly GL, Strasser A. The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells. Cell Death Differ. 2023 Apr;30(4):1033-1046. doi: 10.1038/s41418-023-01122-3. Epub 2023 Feb 4. Erratum in: Cell Death Differ. 2023 Apr;30(4):1096. doi: 10.1038/s41418-023-01137-w. PMID: 36739334; PMCID: PMC10070280. 17: Byskata K, Lukoseviciute M, Tuti F, Zupancic M, Kostopoulou ON, Holzhauser S, Dalianis T. Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited. Cancers (Basel). 2022 Dec 23;15(1):93. doi: 10.3390/cancers15010093. PMID: 36612094; PMCID: PMC9818008. 18: Palomar-Siles M, Heldin A, Zhang M, Strandgren C, Yurevych V, van Dinter JT, Engels SAG, Hofman DA, Öhlin S, Meineke B, Bykov VJN, van Heesch S, Wiman KG. Translational readthrough of nonsense mutant TP53 by mRNA incorporation of 5-Fluorouridine. Cell Death Dis. 2022 Nov 25;13(11):997. doi: 10.1038/s41419-022-05431-2. PMID: 36433934; PMCID: PMC9700717. 19: Roszkowska KA, Piecuch A, Sady M, Gajewski Z, Flis S. Gain of Function (GOF) Mutant p53 in Cancer-Current Therapeutic Approaches. Int J Mol Sci. 2022 Oct 31;23(21):13287. doi: 10.3390/ijms232113287. PMID: 36362074; PMCID: PMC9654280. 20: Barutello G, Di Lorenzo A, Gasparetto A, Galiazzi C, Bolli E, Conti L, Cavallo F. Immunotherapy against the Cystine/Glutamate Antiporter xCT Improves the Efficacy of APR-246 in Preclinical Breast Cancer Models. Biomedicines. 2022 Nov 8;10(11):2843. doi: 10.3390/biomedicines10112843. PMID: 36359363; PMCID: PMC9688020.