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| | APS-2-79 Basic information |
| Product Name: | APS-2-79 | | Synonyms: | APS-2-79;APS-2-79 (hydrochloride);APS 2 79;APS279;APS-279;CS-2444;APS-2-79 hydrochloride >=98% (HPLC);6,7-dimethoxy-N-(2-methyl-4-phenoxyphenyl)quinazolin-4-amine hydrochloride;MAP2K,MAPKK,Inhibitor,Mitogen-activated protein kinase kinase,APS 2 79 hydrochloride,APS279 hydrochloride,inhibit,MEK | | CAS: | 2002381-31-7 | | MF: | C23H22ClN3O3 | | MW: | 423.9 | | EINECS: | | | Product Categories: | | | Mol File: | 2002381-31-7.mol |  |
| | APS-2-79 Chemical Properties |
| storage temp. | Store at -20°C | | solubility | Soluble in DMSO | | form | A crystalline solid |
| | APS-2-79 Usage And Synthesis |
| Description | APS-2-79 is an inhibitor of MAPK signaling dependent on kinase suppressor of Ras (KSR). It inhibits ATPbiotin 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. |
| | APS-2-79 Preparation Products And Raw materials |
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