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Type HazMat fee for 500 gram (Estimated)
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Accessible (Haz class 3, 4, 5 or 8), International USD 200+
Chemical Structure| 5608-24-2 Chemical Structure| 5608-24-2

Structure of PRIMA-1
CAS No.: 5608-24-2

Chemical Structure| 5608-24-2

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PRIMA-1 is a mutant p53 reactivator. It induces apoptosis and inhibits growth of human tumors with mutant p53.

Synonyms: NSC-281668

4.5 *For Research Use Only !

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Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

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Product Details of PRIMA-1

CAS No. :5608-24-2
Formula : C9H15NO3
M.W : 185.22
SMILES Code : O=C1C(CO)(CO)N2CCC1CC2
Synonyms :
NSC-281668
MDL No. :MFCD04974196
InChI Key :RFBVBRVVOPAAFS-UHFFFAOYSA-N
Pubchem ID :322968

Safety of PRIMA-1

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H334
Precautionary Statements:P261-P342+P311
Class:6.1
UN#:2811
Packing Group:

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
OVCAR-3 ovarian cancer cells 2-30 μM 72 hours APR-246 increased the sensitivity of OVCAR-3 cells to cisplatin and reduced the survival index plateau at higher concentrations. PMC4669826
A2780-CP20 ovarian cancer cells 8-60 μM 72 hours APR-246 completely restored the sensitivity of ovarian cancer cells to cisplatin at clinically relevant concentrations. PMC4669826
T24 cells 100-125 μM 24 hours Inhibited RSK4 activation, resulting in decreased cellular cIAP1 and cIAP2 expression PMC4511243
Human GBM cell lines (LN215) 10, 20 μM 7 weeks To assess the impact of sustained versus intermittent exposure to PRIMA-1 on cell proliferation. Results indicated that cells under intermittent exposure remained responsive to PRIMA-1 upon reintroduction, whereas sustained exposure led to resistance. PMC3631679
Human GBM cell lines (LN215) 5, 10, 20 μM 1, 3, 5 days To evaluate the growth inhibitory effect of PRIMA-1 on glioblastoma cells harboring mutant p53 and retaining CDKN2A(ARF) functionality. Results showed significant growth inhibition (98% reduction in cell proliferation) and induction of p53 target genes. PMC3631679

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
CD-1 Nu/Nu mice A2780-CP20 ovarian cancer xenograft model 400 mg/kg/day Intravenous injection APR-246 for 7 consecutive days, cisplatin on days 2 and 6 Combination treatment with APR-246 and cisplatin significantly inhibited tumor growth by 56% and was well tolerated. PMC4669826

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02999893 Oesophageal Carcinoma Phase 1 Phase 2 Recruiting April 30, 2023 Australia, Victoria ... More >> Monash Medical Centre Recruiting Clayton, Victoria, Australia, 3000 Contact: Benjamin Markman          Principal Investigator: Benjamin Markman, MBBS, FRACP          Austin Health Not yet recruiting Heidelberg, Victoria, Australia, 3000 Contact: Niall Tebbutt          Principal Investigator: Niall Tebbutt, MBBS, FRACP          Peter MacCallum Cancer Centre Recruiting Melbourne, Victoria, Australia, 3002 Contact: Lara Lipton, MSc       lara.lipton@petermac.org    Principal Investigator: Lara Lipton, MBBS, FRACP          Sub-Investigator: Michael Michael, MBBS, FRACP          Alfred Hospital Not yet recruiting Prahran, Victoria, Australia, 3000 Contact: Andrew Haydon          Principal Investigator: Andrew Haydon, MBBS, FRACP          Sunshine Hospital Western Health Not yet recruiting Sunshine, Victoria, Australia, 3000 Contact: Lara Lipton       lara.lipton@petermac.org    Principal Investigator: Lara Lipton, MBBS, FRACP Less <<
NCT03588078 Myelodysplastic Syndrome With ... More >>Gene Mutation Acute Myeloid Leukemia With Gene Mutations Myeloproliferative Neoplasm Chronic Myelomonocytic Leukemia Less << Phase 1 Phase 2 Recruiting May 15, 2021 France ... More >> Hôpital Archet 1 Recruiting Nice, France, 06200 Contact: Thomas CLUZEAU, Prof    33492035844    cluzeau.t@chu-nice.fr    Principal Investigator: Pierre Fenaux, Pr          Hôpital Saint Louis - Hématologie Séniors Recruiting Paris, France, 75010 Contact: Pierre Fenaux, MD    033170207022    pierre.fenaux@sls.aphp.fr    Principal Investigator: Pierre Fenaux, MD Less <<
NCT03072043 Myelodysplastic Syndrome ... More >> Acute Myeloid Leukemia Myeloproliferative Neoplasm Chronic Myelomonocytic Leukemia Less << Phase 1 Phase 2 Recruiting May 2021 United States, Florida ... More >> H. Lee Moffitt Cancer Center and Research Institute Recruiting Tampa, Florida, United States, 33612 Contact: Lisa Nardelli    813-745-4731    lisa.nardelli@moffitt.org    Contact: David Sallman, M.D.    813-745-4673    david.sallman@moffit.org    Principal Investigator: David Sallman, M.D.          Sub-Investigator: Rami Komrokji, M.D.          Sub-Investigator: Jeffrey Lancet, M.D.          Sub-Investigator: Alan List, M.D.          Sub-Investigator: Kathy McGraw, Ph.D.          Sub-Investigator: Eric Padron, M.D.          Sub-Investigator: Kendra Sweet, M.D.          Sub-Investigator: Ling Zhang, M.D.          Sub-Investigator: Rachid Baz, M.D.          United States, Maryland The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting Baltimore, Maryland, United States, 21231 Contact: Amy DeZern, M.D.    410-502-7208    adezern1@jhmi.edu    Principal Investigator: Amy DeZern, M.D.          United States, Massachusetts Dana-Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 Contact: David Steensma, M.D.    617-632-5202    dsteensma@partners.org    Principal Investigator: David Steensma, M.D.          United States, New York Weill Medical College of Cornell University Recruiting New York, New York, United States, 10065 Contact: Finola Goudy    212-746-4447    fig4001@med.cornell.edu    Principal Investigator: Gail Roboz, MD          Sub-Investigator: Ellen Ritchie, MD          Sub-Investigator: Sangmin Lee, MD          Sub-Investigator: Pinkal Desai, MD          Sub-Investigator: Michael Samuel, MD          Sub-Investigator: Jeffrey Ball, MD          Sub-Investigator: Sandra Allen-Bard, PA          Sub-Investigator: Natalie Tafel, PA          United States, Ohio Cleveland Clinic Taussig Cancer Center Recruiting Cleveland, Ohio, United States, 44195 Contact: Mikkael A. Sekeres, M.D.    216-445-9353    sekerem@ccf.org    Principal Investigator: Mikkael A. Sekeres, M.D.          United States, Texas University of Texas M.D. Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Heather Schneider, RN    713-792-4478    HNSchneider@mdanderson.or    Principal Investigator: Guillermo Garcia-Manero, MD Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

5.40mL

1.08mL

0.54mL

26.99mL

5.40mL

2.70mL

53.99mL

10.80mL

5.40mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

[1]Izetti P, Hautefeuille A, et al. PRIMA-1, a mutant p53 reactivator, induces apoptosis and enhances chemotherapeutic cytotoxicity in pancreatic cancer cell lines. Invest New Drugs. 2014 Oct;32(5):783-94.

[2]Lambert JM, Gorzov P, et al. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell. 2009 May 5;15(5):376-88.

[3]Izetti P, Hautefeuille A, Abujamra AL, de Farias CB, Giacomazzi J, Alemar B, Lenz G, Roesler R, Schwartsmann G, Osvaldt AB, Hainaut P, Ashton-Prolla P. PRIMA-1, a mutant p53 reactivator, induces apoptosis and enhances chemotherapeutic cytotoxicity in pancreatic cancer cell lines. Invest New Drugs. 2014 Oct;32(5):783-94. doi: 10.1007/s10637-014-0090-9. Epub 2014 May 20. PMID: 24838627.

[4]Furukawa H, Makino T, Yamasaki M, Tanaka K, Miyazaki Y, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mori M, Doki Y. PRIMA-1 induces p53-mediated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation. Cancer Sci. 2018 Feb;109(2):412-421. doi: 10.1111/cas.13454. Epub 2017 Dec 28. PMID: 29168598; PMCID: PMC5797815.

[5]Teoh PJ, Bi C, Sintosebastian C, Tay LS, Fonseca R, Chng WJ. PRIMA-1 targets the vulnerability of multiple myeloma of deregulated protein homeostasis through the perturbation of ER stress via p73 demethylation. Oncotarget. 2016 Sep 20;7(38):61806-61819. doi: 10.18632/oncotarget.11241. PMID: 27533450; PMCID: PMC5308692.

[6]Russo D, Ottaggio L, Foggetti G, Masini M, Masiello P, Fronza G, Menichini P. PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53. Biochim Biophys Acta. 2013 Aug;1833(8):1904-13. doi: 10.1016/j.bbamcr.2013.03.020. Epub 2013 Mar 29. PMID: 23545415.

 

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