Sotorasib (AMG-510) is an Orally Bioavailable KRAS G12C Covalent Inhibitor
The KRAS oncoprotein is a GTPase and an essential mediator of intracellular signaling pathways. KRAS oncoprotein regulates tumor cell growth and survival. However, KRAS also is the most frequently mutated oncogene in cancer and encodes a key signaling protein in tumors. In addition, KRASG12C mutant is present in approximately...
Opnurasib (JDQ-443) is an Orally Active KRAS G12C Inhibitor
Kirsten rat sarcoma (KRAS) is a member of the RAS family. KRAS is a key regulator of signaling pathways responsible for cell proliferation, differentiation, and survival. KRAS mutations are genetic drivers of multiple cancer types, especially colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer (NSCLC)....
Adagrasib (MRTX849), a Potent KRAS G12C Inhibitor for KRAS G12C-mutated Locally Advanced or Metastatic NSCLC Research
On December 12, 2022, FDA granted accelerated approval to Adagrasib (Krazati), for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. In 2021, FDA approved the selective KRASG12C mutant inhibitor Sotorasib (AMG 510) as a second-line treatment of KRASG12C mutation-positive NSCLC. As a result, Adagrasib (MRTX849) is the...
BI-0474 is a Potent KRAS G12C inhibitor
K-Ras protein is a kind of GTPase. Specifically, it is a kind of enzyme that converts nucleotide guanosine triphosphate (GTP) to guanosine diphosphate (GDP). In this way, the K-Ras protein acts like a switch. Besides, KRAS is the most frequently changed homotype in NSCLC cases with RAS mutation. Moreover,...
BI-3406 is an Orally Active and Selective KRAS and SOS1 Interaction Inhibitor
KRAS functions as a molecular switch, cycling between inactive (GDP-bound) and active (GTP-bound) states to transduce extracellular signals via cell-surface receptors. KRAS signaling occurs through engagement with effector proteins that orchestrate intracellular signaling cascades regulating tumor cell survival and proliferation. Mutations in the KRAS gene occur in approximately one of seven...
LC-2 is a First-in-Class PROTAC-Based KRAS G12C Degrader
KRAS gene is one of the most frequently mutated oncogenes in cancer. KRAS encodes a small, membrane-bound GTPase that relays signals from receptor tyrosine kinases (RTKs). It promotes cell proliferation, cell differentiation, or cell survival. In normal cells, KRAS functions as a molecular switch, cycling between an inactive, GDP-bound “off” state and...
SM1-71 is a Multi-Targeted Kinase Inhibitor with Anti-Cancer Activity
In this article, we will introduce a potent TAK1 inhibitor, with a Ki of 160 nM. SM1-71 inhibits MEK1 activities with an IC50 of 142 nM. It also exhibits only weak activity against ERK2 with an IC50 of 1090 nM. Additionally, SM1-71 has an acrylamide warhead in the ortho-position. At the same time, it...