APS-2-79 Property

storage temp. 

Store at -20°C

solubility 

Soluble in DMSO

form 

A crystalline solid

Safety

HS Code 

2933599590

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H361Suspected of damaging fertility or the unborn child

H372Causes damage to organs through prolonged or repeated exposure

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P201Obtain special instructions before use.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

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

P301+P330+P331IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

APS-2-79 Chemical Properties,Usage,Production

Description

APS-2-79 is an inhibitor of MAPK signaling dependent on kinase suppressor of Ras (KSR). It inhibits ATP^biotin binding to KSR2 in KSR2-MEK1 complexes (IC₅₀ = 120 nM), stabilizes KSR2 in an inactive state, and reduces interactions between B-RAF and KSR2-MEK1 complexes. APS-2-79 (5 μM) inhibits KSR-stimulated phosphorylation of MEK and ERK in HEK293H cells. It enhances the efficacy of the MEK inhibitor trametinib , further reducing cell viability in HCT116 and A549 cell lines containing K-Ras mutations, but not B-RAF mutant SK-MEL-239 and A375 cell lines, when used at a concentration of 1 μM.

Uses

APS-2-79 is a modulator of KSR-dependent MAPK signaling, antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation as well as the activation of KSR-bound MEK (mitogen-activated protein kinase).

in vitro

aps-2-79 was found to be able to suppress ksr-stimulated mek and erk phosphorylation. this mapk signalling suppression caused by aps-2-79 was dependent on direct targeting of ksr as an active site mutant, which had been demonstrated to stimulate ksr-based mapk outputs independent of atp-binding, which could significantly diminish the activity of aps-2-79. moreover, the ksr-stimulated mek phosphorylation caused by raf was reduced by the addition of aps-2-79 markedly. in addition, aps-2-79 was no effetive when ksr was absent or when the ksr2(a690f) mutant was used for in vitro assays, indicating that the activity of aps-2-79 was from direct targeting of ksr. however, aps-2-79 was found to lack direct activity against the highly homologous active raf family kinases, such as recombinant braf and craf, or cellular braf(v600e) [1].

IC 50

120 nm

References

[1] dhawan ns, scopton ap, dar ac. small molecule stabilization of the ksr inactive state antagonizes oncogenic ras signalling. nature. 2016 sep 1;537(7618):112-116.