Other Name(s): B-Raf
Drug Target Analysis Report Drug Target Analysis Report Content

About the Target

The BRAF gene plays a critical role in the MAPK/ERK signaling pathway, which regulates cell cycle control, proliferation, and cellular migration [1]. The presence of the BRAFV600E mutation results in a constant activation of the MAPK/ERK pathway, leading to uncontrolled cellular growth and inhibition of apoptosis [1]. This mutation can be targeted with specific inhibitors to increase apoptotic activity [1, 2].

BRAF mutations are commonly found in melanoma tumors, where the MAPK pathway is crucial for tumor development [2]. However, other pathways, such as the PI3K pathway, can also contribute to the resistance of melanoma to BRAF and MEK inhibition [2].

The expression of the PGC-1alpha gene, which is involved in cellular metabolism, is influenced by oncogenes, tumor suppressors, lineage-specific regulators, and cellular stresses [3]. The presence of BRAF mutations can regulate the expression of PGC-1alpha, which in turn affects processes like the epithelial-to-mesenchymal transition and hypoxia-inducible factor 1alpha [3].

In thyroid carcinoma, mutations in key components of the MAPK pathway, including BRAF, play a central role in tumorigenesis [4]. Tyrosine kinase inhibitors and BRAF inhibitors have been investigated as potential treatments for advanced thyroid carcinoma [4].

Different isoforms of BRAF, such as BRAFV600E-ref, X1, and X2, have varying levels of protein expression and degradation rates [5]. The presence of certain domains, such as CR3-X2, can decrease the levels of BRAF protein [5]. The degradation of the X2 isoform is faster than the other isoforms and is mediated through the ubiquitin-proteasome pathway, which can be rescued by mutagenesis of a specific amino acid [5].

Overall, understanding the role of BRAF mutations and their impact on signaling pathways and gene expression is crucial for developing targeted therapies and improving treatment outcomes in various cancers.
Based on the context information provided, some key viewpoints about BRAF are:

BRAF is part of the ERBB/KRAS/BRAF/MAPK signaling axis, and alterations in this pathway are commonly observed in colorectal cancer (CRC) [6].
Mutations in BRAF or KRAS within a primary CRC predict resistance to certain monoclonal antibody therapies used to block ERBB1(EGFR)/KRAS/BRAF/MAPK signaling in stage IV patients [6].
Activation mutations in PIK3CA, which is part of the PI3 Kinase pathway, are seen in a significant portion of non-hypermutated CRCs and often co-occur with alterations in the ERBB/KRAS/BRAF/MAPK axis [6].
Inhibiting Cox-2, which is overexpressed in CRCs, and increasing the expression of 15-PGDH can help diminish the levels of PGE2, which is associated with increased proliferation and angiogenesis in CRC [6].
Specific inhibitors can be used to target different classes of BRAF or MEK mutations, and the therapeutic approach depends on whether the mutation is classified as an "activator" or "amplifier" [7].
The signaling pathways involving hedgehog, BRAF/Ras/MAPK, EGFR, Wnt, and Akt can interact and regulate each other, suggesting molecular crosstalk among these pathways [8].
B-Raf and C-Raf kinases have different affinities for various Ras family members, with B-Raf showing high affinity for mutant K-Ras and possible interaction with mutant H-Ras under certain conditions [9].
ERK1/2-mediated feedback inhibition regulates the signaling cascade involving SOS, RAF, and MEK1/2, preventing hyperstimulation of ERK signaling. However, different classes of BRAF mutants have varying susceptibility to feedback inhibition mechanisms [10].

Note: The viewpoints have been merged and summarized from various context sources provided. The numbered references indicate the source of information for each viewpoint.

Figure [1]

Figure [2]

Figure [3]

Figure [4]

Figure [5]

Figure [6]

Figure [7]

Figure [8]

Figure [9]

Figure [10]

Note: If you are interested in the full version of this target analysis report, or if you'd like to learn how our AI-powered BDE-Chem can design therapeutic molecules to interact with the BRAF target at a cost 90% lower than traditional approaches, please feel free to contact us at BD@silexon.ai.

More Common Targets

ABCB1 | ABCG2 | ACE2 | AHR | AKT1 | ALK | AR | ATM | BAX | BCL2 | BCL2L1 | BECN1 | BRAF | BRCA1 | CAMP | CASP3 | CASP9 | CCL5 | CCND1 | CD274 | CD4 | CD8A | CDH1 | CDKN1A | CDKN2A | CREB1 | CXCL8 | CXCR4 | DNMT1 | EGF | EGFR | EP300 | ERBB2 | EREG | ESR1 | EZH2 | FN1 | FOXO3 | HDAC9 | HGF | HMGB1 | HSP90AA1 | HSPA4 | HSPA5 | IDO1 | IFNA1 | IGF1 | IGF1R | IL17A | IL6 | INS | JUN | KRAS | MAPK1 | MAPK14 | MAPK3 | MAPK8 | MAPT | MCL1 | MDM2 | MET | MMP9 | MTOR | MYC | NFE2L2 | NLRP3 | NOTCH1 | PARP1 | PCNA | PDCD1 | PLK1 | PRKAA1 | PRKAA2 | PTEN | PTGS2 | PTK2 | RELA | SIRT1 | SLTM | SMAD4 | SOD1 | SQSTM1 | SRC | STAT1 | STAT3 | STAT5A | TAK1 | TERT | TLR4 | TNF | TP53 | TXN | VEGFA | YAP1