Raf

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor

30 views | Dec 12 2023

In this study, a series of EPHA2 kinase inhibitors, including derivatives of NVP-BHG712 and triazine-based compounds, were synthesized and evaluated, revealing eight inhibitors with low-nanomolar affinities (KD <10 nM) that demonstrated promising effects in controlling human colon carcinoma, highlighting their potential as therapeutic tools in cancer research. [Read the Full Post]

Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases

0 views | Nov 14 2023

This research investigates the potential for covalent inhibitors targeting specific cysteine residues in key kinases of the ERK pathway to overcome resistance mechanisms and enhance the efficacy of cancer treatment. [Read the Full Post]

BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study

67 views | Sep 16 2023

The VEM-PLUS study found that combining vemurafenib with cytotoxic chemotherapy or RAF- or mTOR-targeting agents did not significantly improve overall survival or progression-free survival compared to vemurafenib monotherapy in patients with solid tumors harboring BRAF V600E mutations. [Read the Full Post]

Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases

62 views | Sep 02 2023

This study presents a systematic analysis of the covalent ligandabilities of ERK pathway kinases, identifying reactive cysteine residues and proposing potential scaffolds for the design of novel covalent inhibitors, thereby providing valuable insights for the development of targeted therapies against tumorigenesis. [Read the Full Post]

Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study

26 views | Aug 23 2023

The combination therapy of naporafenib and trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma, with manageable adverse events and ongoing research on prophylactic strategies to address skin-related side effects. [Read the Full Post]

Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib

0 views | Aug 23 2023

Type II RAF inhibitors, such as tovorafenib and naporafenib, exhibit potent inhibitory effects against CRAF but display reduced potency against ARAF, highlighting their potential clinical implications and suggesting a relative sparing of ARAF by multiple drugs in this class. [Read the Full Post]

SB202190 Predicts BRAF-Activating Mutations in Primary Colorectal Cancer Organoids via Erk1-2 Modulation

42 views | Jul 09 2023

The study demonstrated that the p38 inhibitor SB202190 can predict BRAF-activating mutations in colorectal cancer organoids and has potential as a more effective long-term inhibitor of BRAF-mutated organoid growth compared to specific BRAF inhibitors. [Read the Full Post]

Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS

41 views | Jul 06 2023

RAS proteins, including KRAS, HRAS, and NRAS, function as GTPases and play crucial roles in cell signaling pathways involved in growth, division, and survival, with RAS mutations being common in various cancers, particularly KRAS mutations in lung, colorectal, and pancreatic cancers. [Read the Full Post]

Differential regulation of histamine H1 receptor-mediated ERK phosphorylation by Gq proteins and arrestins

74 views | Jul 02 2023

The study revealed that H1 receptor-mediated ERK phosphorylation is differentially regulated by Gq protein/Ca2+/PKC and GRK/arrestin/clathrin/Raf/MEK pathways, potentially determining the early and late phases of histamine-induced allergic and inflammatory responses. [Read the Full Post]

Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma

85 views | Jun 07 2023

Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis, and the limited efficacy of available therapies in patients with moderate liver dysfunction highlights the need for improved treatment algorithms and novel therapies specifically designed for this patient population. [Read the Full Post]