PRIMA-1 Property

Melting point:

146-147 °C

Boiling point:

353.7±17.0 °C(Predicted)

Density 

1.32±0.1 g/cm3(Predicted)

storage temp. 

Inert atmosphere,2-8°C

solubility 

H2O: >10mg/mL

pka

13.68±0.10(Predicted)

form 

solid

color 

white to off-white

Water Solubility 

Soluble in water at 10mg/ml

Sensitive 

Light Sensitive

Safety

Hazard Codes 

Xn

Risk Statements 

22-43

Safety Statements 

36/37

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H334May cause allergy or asthma symptoms or breathing difficulties if inhaled

PRIMA-1 Chemical Properties,Usage,Production

Uses

PRIMA-1 is a reactivator of p53 and inducer of apoptosis.

Definition

ChEBI: 2,2-bis(hydroxymethyl)-1-azabicyclo[2.2.2]octan-3-one is a member of quinuclidines and a cyclic ketone.

Biological Activity

Selectively restores mutant p53 activity in tumor cells via activation of Bax and PUMA. Induces apoptosis and inhibits growth of human tumors with mutant p53.

in vitro

the substantial increase in saos-2-his-273-cells death could be noticed after being treated with 125 μm prima-1 for 48 hours. tunel staining revealed that such tumor-cell death was primarily triggered by apoptosis. prima-1 could also restore the transcriptional transactivation function to mutant p53 in vitro. [2]

in vivo

to assess the effect of prima-1 on human tumor xenografts, mice were inoculated with saos-2-his-273 cells expressing mutant p53. the mice then received prima-1 treatment at intra-tumor does of 20 mg/kg or i.v. doses of 20 and 100 mg/kg twice a day for three days. compared with the control group, the average tumor volume decreased from 555.7 mm3 to 11.7 (100 mg/kg) and 53 (20 mg/kg) mm3 after i.v. injections of prima-1. intra-tumor injections of prima-1 also decreased the average tumor volume to 5.3 mm3. [2]

IC 50

the value varied among different tumor type. in saos-2-his-273 cells, prima-1 induced cell death with an ic50 of over 15 m.

storage

Store at +4°C

References

[1] bykov v, issaeva n, zache n, shilov a, hultcrantz m, bergman j, selivanova g, wiman kg. reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs. j biol chem. 2005 aug; 280(34): 30384–91.
[2] bykov v, issaeva n, shilov a, hultcrantz m, pugacheva e, chumakov p, bergman j, wiman kg, selivanova g. restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. nat med. 2002 mar; 8(3):282-8.
[3] lehmann s, bykov v, ali d, andren o, cherif h, tidefelt u, uggla b, yachnin j, juliusson g, moshfegh a, paul c, wiman kg, andersson po. targeting p53 in vivo: a first-in-human study with p53-targeting compound apr-246 in refractory hematologic malignancies and prostate cancer. j clin oncol. 2012. doi: 10.1200/jco.2011.40.7783.