PhiKan-083 Hydrochloride Property

Boiling point:

401.0±27.0 °C(Predicted)

Density 

1.09±0.1 g/cm3(Predicted)

storage temp. 

Store at 4°C

solubility 

<13.74mg/ml in H2O; <27.48mg/ml in DMSO

form 

solid

pka

9.71±0.10(Predicted)

color 

White

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P501Dispose of contents/container to..…

PhiKan-083 Hydrochloride Chemical Properties,Usage,Production

Uses

PhiKan-083 is a p53 stabilizing agent. PhiKan-083 preferentially binds mutated (Y220C) p53 over wild-type p53 at a site distinct from functional DNA/protein interaction regions. PhiKan-083 slows rate of thermal denaturation of p53-Y220C.

Biological Activity

ki: ≈ 150 mphikan 083 is a critical p53 stabilizing agent by bonding its mutation y220cthe mutation y220c of p53 exists a surface cavity that destabilizes the protein by 4 kcal/mol, at a site that is not functional. a p53 stabilizing agent binding it is able to slow rate of thermal denaturation [1].

in vitro

isothermal titration of phikan083 with t-p53c-y220c exhibited 1:1 stoichiometry and a kd of 125 ± 10 m. phikan083 stabilized t-p53c-y220c in a concentration-dependent manner. in a simple binding model for phikan083 (t-p53c-y220c at 310 k (37°c)), in the absence of ligand, the protein gave a half-life of 3.8 min, while it increased to 15.7 min at saturating concentrations of phikan083. this is a proposed anticancer drug that could be developed for the y220c mutant using p53 stabilizing agent. the site of mutation in the oncogenic y220c mutant phikan083 binds with reasonable affinity is a druggable target. interestingly, the site of mutation does not exist in a region of the protein that is functionally important, it will be an excellent target for drug stabilization therapy. this suggests the crystal structure of the complex will be a fresh start for further rounds of drug design and refinement [1].

References

[1] boeckler fm, joerger ac, jaggi g, rutherford tj, veprintsev db, fersht ar. targeted rescue of a destabilized mutant of p53 by an in silico screened drug. proc natl acad sci u s a. 2008 jul 29; 105(30):10360-5.