KRAS-Targeted Library
Files to download
Preferred format
Desirable size of the custom library selection
Number of compounds
Amount
Volume
uL
Description
ChemDiv’s KRAS-Targeted Library contains 11,000 compounds.
The small G-proteins KRas, HRas, and NRas function as GDP–GTP regulated binary switches in many signal transduction pathways that govern cell growth and differentiation. The alternation between the GDP-bound ‘off’ state and the GTP-bound ‘on’ state is controlled by the guanine nucleotide exchange factors (GEFs) SOS1 and SOS2, which catalyze the exchange of GDP for GTP, and by GTPase-activating proteins (GAPs), which terminate the ‘on’ state by catalyzing the hydrolysis of GTP to GDP. In the active state, Ras signals to a spectrum of functionally diverse downstream effector proteins, such as Raf, PI3K, and Ral-GDS. The catalytic domain of Ras is highly homologous between the three Ras isoforms KRas, HRas, and NRas, however major differences are found in the C-terminal hypervariable region (HVR) of these proteins. The latter part of these proteins is involved in membrane association, which is a critical requirement for downstream signaling.
The gain of function mutations in Ras proteins are frequently found in human cancers and represent poor prognosis markers for patients. Mutations of the KRas isoform constitute some of the most common aberrations among all human cancers and occur in three of the top four neoplasms that cause cancer deaths in the USA: lung, colon, and pancreatic cancer. There is strong evidence for inhibiting Ras as a therapeutic strategy and, consequently, intensive drug discovery efforts have been directed toward targeting Ras.
The small G-proteins KRas, HRas, and NRas function as GDP–GTP regulated binary switches in many signal transduction pathways that govern cell growth and differentiation. The alternation between the GDP-bound ‘off’ state and the GTP-bound ‘on’ state is controlled by the guanine nucleotide exchange factors (GEFs) SOS1 and SOS2, which catalyze the exchange of GDP for GTP, and by GTPase-activating proteins (GAPs), which terminate the ‘on’ state by catalyzing the hydrolysis of GTP to GDP. In the active state, Ras signals to a spectrum of functionally diverse downstream effector proteins, such as Raf, PI3K, and Ral-GDS. The catalytic domain of Ras is highly homologous between the three Ras isoforms KRas, HRas, and NRas, however major differences are found in the C-terminal hypervariable region (HVR) of these proteins. The latter part of these proteins is involved in membrane association, which is a critical requirement for downstream signaling.
The gain of function mutations in Ras proteins are frequently found in human cancers and represent poor prognosis markers for patients. Mutations of the KRas isoform constitute some of the most common aberrations among all human cancers and occur in three of the top four neoplasms that cause cancer deaths in the USA: lung, colon, and pancreatic cancer. There is strong evidence for inhibiting Ras as a therapeutic strategy and, consequently, intensive drug discovery efforts have been directed toward targeting Ras.
