WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406958
Description: APS-2-79 is a KSR-dependent MAPK modulator. APS-2-79 modulates KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK (mitogen-activated protein kinase kinase). APS-2-79 increased the potency of several MEK inhibitors specifically within Ras-mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. Co-targeting of enzymatic and scaffolding activities within Ras-MAPK signalling complexes is a therapeutic strategy for overcoming Ras-driven cancers.
MedKoo Cat#: 406958
Chemical Formula: C23H21N3O3
Exact Mass: 387.1583
Molecular Weight: 387.439
Elemental Analysis: C, 71.30; H, 5.46; N, 10.85; O, 12.39
Synonym: APS-2-79; APS 2-79; APS2-79; APS-279; APS 279; APS279.
IUPAC/Chemical Name: 6,7-Dimethoxy-N-(2-methyl-4-phenoxyphenyl)quinazolin-4-amine
InChi Key: PEKZLFZZBGBOPJ-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H21N3O3/c1-15-11-17(29-16-7-5-4-6-8-16)9-10-19(15)26-23-18-12-21(27-2)22(28-3)13-20(18)24-14-25-23/h4-14H,1-3H3,(H,24,25,26)
SMILES Code: CC1=CC(OC2=CC=CC=C2)=CC=C1NC3=C4C=C(OC)C(OC)=CC4=NC=N3
Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes. Kinase suppressor of Ras (KSR) is a MAPK scaffold that is subject to allosteric regulation through dimerization with RAF. Direct targeting of KSR could have important therapeutic implications for cancer.
1: KSR Mutations Guide Development of RAS Pathway Antagonists. Cancer Discov.
2016 Oct;6(10):1079. PubMed PMID: 27591198.
2: Dhawan NS, Scopton AP, Dar AC. Small molecule stabilization of the KSR
inactive state antagonizes oncogenic Ras signalling. Nature. 2016 Aug
24;537(7618):112-116. doi: 10.1038/nature19327. [Epub ahead of print] PubMed