JAK3 Inhibitor Property

Melting point:

230 °C

Boiling point:

470.3±45.0 °C(Predicted)

Density 

1.576±0.06 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

DMSO: soluble1mg/mL, clear (warmed)

pka

8.57±0.31(Predicted)

form 

powder

color 

white to brown

InChIKey

CBIAKDAYHRWZCU-UHFFFAOYSA-N

CAS DataBase Reference

211555-04-3

Safety

Hazard Codes 

Xn

Risk Statements 

22-36/37/38

Safety Statements 

26

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

3

HS Code 

2933.59.8000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

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

JAK3 Inhibitor Chemical Properties,Usage,Production

Description

WHI-P154 is a quinazoline derivative that exhibits immunosuppressive effects by selectively inhibiting JAK3 (IC₅₀ = 1.8 μM versus IC₅₀s > 10 μM for JAK1 and JAK2). It has been reported to inhibit additional kinases including EGFR (IC₅₀ = 4 nM) and VEGFR as well as the non-receptor tyrosine kinases, Abl, Lck, and Src. WHI-P154 is cytotoxic to human glioblastoma cells (IC₅₀ = 813 nM) and has been used to induce the differentiation of neuronal precursor cells.

Uses

WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM and also inhibits EGFR with IC50 of 4 nM.

Uses

WHI-P154 can act as antileukemic agent with apoptosis inducing activity.

Biochem/physiol Actions

WHI-P154 is a specific inhibitor of JAK3 (IC50 = 1.8 μM) with no inhibitory activity against JAK1 or JAK2. WHI-P154 enhances myogenic differentiation of C2C12 mouse myoblast cells, and induces differentiation of neural progenitor cells. The compound WHI-P154 dose dependently inhibits expression of iNOS and NO production in LPS-challenged macrophages.

in vitro

kinase assays show that whi-p154 is not a specific inhibitor. besides jak3, it also inhibits many other kinases, including egfr, abl, lck, src and vegfr. whi-p154 inhibits egfr with ic50 value of 4nm. the specificity of whi-p154 has not been shown in cell-based assays either [1].

storage

Store at RT

References

[1] changelian ps, moshinsky d, kuhn cf, flanagan me, munchhof mj, harris tm, whipple da, doty jl, sun j, kent cr, magnuson ks, perregaux dg, sawyer ps, kudlacz em. the specificity of jak3 kinase inhibitors. blood. 2008 feb 15;111(4):2155-7.
[2] narla rk, liu xp, myers de, uckun fm. 4-(3'-bromo-4'hydroxylphenyl)-amino-6,7-dimethoxyquinazoline: a novel quinazoline derivative with potent cytotoxic activity against human glioblastoma cells. clin cancer res. 1998 jun;4(6):1405-14.