CAS NO: | 5608-24-2 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 185.22 |
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Formula | C9H15NO3 |
CAS No. | 5608-24-2 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 37 mg/mL (199.8 mM) |
Water: 37 mg/mL (199.8 mM) | |
Ethanol: N/A | |
Solubility (In vivo) | Prima 1; Prima1; Prima-1 |
Synonyms | 2,2-Bis(hydroxymethyl)-3-quinuclidinone |
In Vitro | In vitro activity: PRIMA-1 is converted to compounds that form adducts with thiols in mutant p53. Modification of thiol groups in mutant p53 by PRIMA-1 conversion products is sufficient to restore its tumor suppressor activity. PRIMA-1 inhibits the growth of pancreatic cancer cell lines and induces cell cycle arrest and decreases DNA synthesis. It selectively induces apoptosis and cell death in mutant p53-expressing pancreatic cancer cells and also leads to activation of p53-dependent apoptotic pathways. PRIMA-1 enhances the cytotoxicity of chemotherapeutic agents active against mutant p53 pancreatic cancer cells. PRIMA-1 has antileukemic properties in acute promyelocytic leukemia-derived NB4 cells. PRIMA-1-triggered apoptosis is in a dose-dependent and time-dependent manner as indicated by the MTT assay and annexin-V staining. Apoptosis induction by PRIMA-1 is associated with caspase-9, caspase-7 activation and PARP cleavage. PRIMA-1 does not show any significant apoptotic effect in normal human peripheral blood mononuclear cells. Kinase Assay: PRIMA-1 is a mutant p53 reactivator, restores the sensitivity of TP53 mutant-type thyroid cancer cells to the histone methylation inhibitor 3-Deazaneplanocin A. Cell Assay: Cells [mutant p53 expressing pancreatic cancer cell lines PANC-1 (p.R273H) and BxPC-3 (p.Y220C) and the wild type p53-expressing Capan-2 cells (wtp53)] are kept at a temperature of 37 °C, a minimum relative humidity of 95 %, and an atmosphere of 5 % CO2 in air. Cell viability is measured by MTT assay after treatment with PRIMA-1. Briefly, cells are seeded in each well of 96-well plates in 100 μl culture medium and incubated overnight at 37 °C in an atmosphere of 5 % CO2. The next day, the medium is removed and cells washed with PBS and treated with vehicle control(DMSO, dimethylsulfoxide) or different concentrations of PRIMA-1 for 12 to 48 h; the medium is replaced with MTT solution diluted in medium once the treatment is completed. The plates are further incubated at 37 °C under 5 % CO2 for 4 h and then left at room temperature until completely dry. DMSO was then added and the absorbance is read at 492 nm using a microplate enzyme-linked immunoassay reader (ELISA). The relative growth activity is determined as the percentage absorbance of treated cells compared to that of vehicle treated cells (control). |
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In Vivo | PRIMA-1 (Prima-1) is a p53-modulating agent. 150 or 300 ppm PRIMA-1 significantly suppresses (P < 0.0001) lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Administration of 150 or 300 ppm PRIMA-1 significantly suppresses NNK-induced total lung adenocarcinoma formation by 57% or 62% (P<0.0001), respectively, after 17 weeks of exposure and by 39% or 56% (P < 0.0001), respectively, after 34 weeks of exposure. As with administration of the lower (50 ppm) dose of CP-31398, administration of the lower (150 ppm) dose of PRIMA-1also slightly increases the number of NNK-induced lung adenomas. Intravenous (i.v.) injections of PRIMA-1 in mice does not cause any obvious changes in weight or behavior compared with untreated animals. PRIMA-1 has in vivo antitumor activity in this animal tumor model. It suppresses in vivo tumor growth in a mutant p53-dependent manner. |
Animal model | SCID mice |
Formulation & Dosage | Dissolved in PBS; 1, 10, 20 and 100 mg/kg; i.v. injection |
References | Invest New Drugs. 2014 Oct;32(5):783-94; Cancer Cell. 2009 May 5;15(5):376-88; Nat Med. 2002 Mar;8(3):282-8; Neoplasia. 2013 Sep;15(9):1018-27. |