Raf
RAF kinases act downstream of RAS and relay signals through the RAF-MEK-ERK/MAPK cascade to regulate cell growth, survival, and differentiation[1]. Mechanistically, RAF activation depends on phosphorylation, conformational control, membrane recruitment, and kinase-domain dimerization, which provides an allosteric mechanism for catalytic activity[1]. In cancer models, mutant BRAF tumors depend on RAF-MEK-ERK signaling, whereas ATP-competitive RAF inhibitors inhibit ERK signaling in mutant BRAF cells but enhance signaling in wild-type BRAF cells through RAF dimer transactivation[2]. Compared with related isoforms, BRAF has the highest basal kinase activity, while ARAF shows a cell-type-dependent role in MAPK activity and cell migration[3]. CRAF/RAF1 differs further because KRAS-mutant tumor subsets depend on CRAF growth functions, and kinase-dead but not dimer-defective CRAF rescues growth inhibition[4]. For experimental applications, RAF inhibitors therefore serve as pathway probes, but study design should distinguish mutant BRAF inhibition from wild-type RAF dimer activation[2][5].
References:
- [1]. Lavoie H, et al. Regulation of RAF protein kinases in ERK signalling. Nat Rev Mol Cell Biol. 2015 May;16(5):281-98. [Content Brief]
- [2]. Poulikakos PI, et al. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010 Mar 18;464(7287):427-30. [Content Brief]
- [3]. Mooz J, et al. Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration. Sci Signal. 2014 Aug 5;7(337):ra73. [Content Brief]
- [4]. Venkatanarayan A, et al. CRAF dimerization with ARAF regulates KRAS-driven tumor growth. Cell Rep. 2022 Feb 8;38(6):110351. [Content Brief]
- [5]. Karoulia Z, et al. An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling. Cancer Cell. 2016 Sep 12;30(3):485-498. [Content Brief]
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Raf Related Products (120)
Related Products (120)
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Antibodies (2)
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RAF709 (Standard)
0 ImagesCat. No.: HY-100510RCAS No.: 1628838-42-5RAF709 (Standard) is the analytical standard of RAF709 (HY-100510). This product is intended for research and analytical applications. RAF709 is a potent, selective, and efficacious RAF inhibitor with IC50s of 0.4 nM and 0.5 nM for BRAF and CRAF, respectively. Antitumor efficacy.
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Dabrafenib (Standard)
0 ImagesSynonyms: GSK2118436A (Standard); GSK2118436 (Standard)
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Regorafenib (Standard)
0 ImagesSynonyms: BAY 73-4506 (Standard)Regorafenib (Standard) is the analytical standard of Regorafenib. This product is intended for research and analytical applications. Regorafenib (BAY 73-4506) is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC50 values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib shows very robust antitumor and antiangiogenic activity.
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Cefotetan (Standard)
0 ImagesCefotetan (Standard) is the analytical standard of Cefotetan. This product is intended for research and analytical applications. Cefotetan is a semisynthetic cephamycin antibiotic that exerts its bactericidal effects by inhibition of cell-wall synthesis.
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Belvarafenib (Standard)
0 ImagesCat. No.: HY-109080RCAS No.: 1446113-23-0Synonyms: HM95573 (Standard); GDC-5573 (Standard); RG6185 (Standard)Belvarafenib (Standard) is the analytical standard of Belvarafenib (HY-109080). This product is intended for research and analytical applications. Belvarafenib (HM95573) is a potent and pan RAF (Rapidly Accelerated Fibrosarcoma) inhibitor, with IC50s of 56 nM, 7 nM and 5 nM for B-RAF, B-RAFv600E and C-RAF respectively.
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BRAF inhibitor (Standard)
0 ImagesCat. No.: HY-10247RCAS No.: 918505-61-0BRAF inhibitor (Standard) is the analytical standard of BRAF inhibitor (HY-10247). This product is intended for research and analytical applications. BRAF inhibitor (Compound P-0850) is a B-Raf inhibitor with anti-tumor activity.
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IHMT-RAF-128
0 ImagesCat. No.: HY-164484CAS No.: 2479289-15-9IHMT-RAF-128, a highly potent pan-RAF inhibitor. IHMT-RAF-128 shows potent antitumor efficacy in xenograft mouse tumor models without causing any apparent toxicities.
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DPQZ
0 ImagesCat. No.: HY-116664CAS No.: 1431362-93-4
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Encorafenib (Standard)
0 ImagesSynonyms: LGX818 (Standard)Encorafenib (Standard) is the analytical standard of Encorafenib. This product is intended for research and analytical applications. Encorafenib (LGX818) is a highly potent BRAF inhibitor with selective anti-proliferative and apoptotic activity in cells expressing BRAFV600E (EC50=4 nM).
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Dabrafenib Mesylate (Standard)
0 ImagesSynonyms: GSK2118436 Mesylate (Standard); GSK 2118436B (Standard)
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PLX-4720-d7
0 ImagesCat. No.: HY-51424SCAS No.: 1304096-50-1PLX-4720-d7 is the deuterium labeled PLX-4720. PLX-4720 is a potent and selective inhibitor of?B-RafV600E?with?an IC50?of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-RafV600E than wild-type B-Raf.
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RMC-7977 (Standard)
0 ImagesCat. No.: HY-156498RCAS No.: 2765082-12-8RMC-7977 (Standard) is the analytical standard of RMC-7977 (HY-156498). This product is intended for research and analytical applications. RMC-7977 is an orally active triple-complex RAS inhibitor that can simultaneously bind to cyclophilin A (CYPA) (Kd = 195 nM) and KRAS (G12V) (Kd = 292 μM). It exhibits broad-spectrum inhibitory activity against KRAS, NRAS, and HRAS proteins and their various wild-type and mutant variants. RMC-7977 induces apoptosis by inhibiting the phosphorylation of ERK, CRAF, and RSK, as well as increasing PARP cleavage. This leads to tumor regression, reduces resistance in KRASG12C cancer models, and demonstrates good tolerability across various RAS cancer models.
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BI-882370 (Standard)
0 ImagesCat. No.: HY-107779RCAS No.: 1392429-79-6BI-882370 (Standard) is the analytical standard of BI-882370 (HY-107779). This product is intended for research and analytical applications. BI-882370 is a potent and selective RAF Kinase inhibitor that binds to the ATP binding site of the Kinase positioned in the DFG-out (inactive) conformation of the BRAF Kinase. BI-882370 (BI 882370) inhibits the oncogenic BRAFV600E-mutant, the WT BRAF and CRAF Kinases with IC50s of 0.4, 0.8, and 0.6 nM, respectively. BI-882370 also inhibits SRC family Kinases.
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Regorafenib Hydrochloride (Standard)
0 ImagesSynonyms: BAY 73-4506 hydrochloride (Standard)Regorafenib (Hydrochloride) (Standard) is the analytical standard of Regorafenib (Hydrochloride). This product is intended for research and analytical applications. Regorafenib Hydrochloride (BAY 73-4506 hydrochloride) is a multi-target inhibitor for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1 with IC50s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM, respectively.
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AFG210
0 ImagesCat. No.: HY-18817CAS No.: 228400-22-4AFG210 is a potent multi-target kinase inhibitor that primarily inhibits Abl kinase (IC50=330 nM), and also has inhibitory effects on other kinases such as B-Raf, C-Raf, FGFR-1, RET and VEGF receptors. AFG210 can be used to study chronic myeloid leukemia and other diseases with abnormal activation of Abl kinase.
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PLX-4720 (Standard)
0 ImagesPLX-4720 (Standard) is the analytical standard of PLX-4720. This product is intended for research and analytical applications. PLX-4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-RafV600E than wild-type B-Raf.
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Azaspirene
0 ImagesCat. No.: HY-N15264CAS No.: 461644-34-8Synonyms: (-)-AzaspireneAzaspirene ((-)-Azaspirene) is an angiogenesis and Raf-1 activation inhibitor isolated from the fungus Neosartorya sp. Azaspirene inhibits vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) migration and Raf-1 activation, but has no effect on the activation of kinase insert domain-containing receptor/fetal liver kinase 1 (VEGF receptor 2).
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GW 5074 (Standard)
0 ImagesCat. No.: HY-10542RCAS No.: 220904-83-6GW 5074 (Standard) is the analytical standard of GW 5074 (HY-10542). This product is intended for research and analytical applications. GW 5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, and has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms.
