K-Ras(G12C) inhibitor 9 Property

Boiling point:

656.3±65.0 °C(Predicted)

Density 

1.68±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

Soluble in DMSO

form 

crystalline solid

pka

9.68±0.20(Predicted)

color 

White to off-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

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

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

K-Ras(G12C) inhibitor 9 Chemical Properties,Usage,Production

Description

K-Ras(G12C) inhibitor 9 is an irreversible, allosteric inhibitor of the K-Ras(G12C) mutant that causes 100% modification of the protein when used at 10 μM for 24 hours in vitro. K-Ras is a small GTPase that cycles between a GTP-bound active state and a GDP-bound inactive state to turn on downstream Raf kinases to drive cell growth. A G12C mutation in K-Ras blocks GTP hydrolysis, activates K-Ras, and promotes carcinogenesis. Similar K-Ras(G12C) inhibitors significantly reduce GTP affinity relative to GDP, decrease Raf binding, and lower cell viability while increasing apoptosis.

Uses

N-[1-[2-[(4-Chloro-5-iodo-2-methoxyphenyl)amino]acetyl]-4-piperidinyl]ethenesulfonamide is an allosteric inhibitor of tumor-promoting K-Ras(G12c).

in vitro

k-ras(g12c) inhibitor 9 belongs to a series of small molecules, which irreversibly compete with gtp and gdp for binding to a common oncogenic k-ras(g12c) mutant and blocked the association of b-raf and c-raf with k-ras(g12c). k-ras(g12c) inhibitor 9 (10 μm) decreased viability and increased apoptosis of g12c mutations-containing lung cancer cell lines (h1792, calu-1, h358, and h23) [1].

target

k-ras(g12c)

References

1. ostrem jm, peters u, sos ml, wells ja, shokat km. k-ras(g12c) inhibitors allosterically control gtp affinity and effector interactions. nature. 2013;503(7477):548-51. 2. hunter jc, gurbani d, ficarro sb, carrasco ma, lim sm, choi hg, et al. in situ selectivity profiling and crystal structure of sml-8-73-1, an active site inhibitor of oncogenic k-ras g12c. proc natl acad sci u s a. 2014;111(24):8895-900. 3. lim sm, westover kd, ficarro sb, harrison ra, choi hg, pacold me, et al. therapeutic targeting of oncogenic k-ras by a covalent catalytic site inhibitor. angew chem int ed engl. 2014;53(1):199-204.