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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I194496
0 ImagesI194496 is a potent cystathionine γ-lyase (CSE) inhibitor, with an IC50 of 0.79 mM. I194496 can inhibit the growth of human TNBC cells via the dual targeting PI3K/Akt and Ras/Raf/ERK pathway and suppress the metastasis of human TNBC cells via down-regulating Anxa2/STAT3 and VEGF/FAK/Paxillin signaling pathways.
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Raf inhibitor 2
0 ImagesRaf inhibitor 2 is a potent raf kinase (IC50<1.0 μM) inhibitor, compound 32, extracted from patent EP1003721B1. Raf inhibitor 2 can be used for cancer research.
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Rineterkib hydrochloride
0 ImagesRineterkib hydrochloride (compound B) is an orally available ERK1 and ERK2 inhibitor in the treatment of a proliferative disease characterized by activating mutations in the MAPK pathway. The activity is particularly related to the treatment of KRAS-mutant NSCLC, BRAF-mutant NSCLC, KRAS-mutant pancreatic cancer, KRAS-mutant colorectal cancer (CRC) and KRAS-mutant ovarian cancer. Rineterkib hydrochloride can also inhibit RAF.
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RAS/RAS-RAF-IN-1
0 ImagesCat. No.: HY-138294CAS No.: 2447039-81-6RAS/RAS-RAF-IN-1 is a potent RAS and RAS-RAF inhibitor. RAS/RAS-RAF-IN-1 has a KD of 5.0 μΜ-15 μΜ for cyclophilin A (CYPA) binding affinity. RAS/RAS-RAF-IN-1 has antitumor activity.
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Vem-L-Cy5
0 ImagesVem-L-Cy5 (compound 3)，modified with the NIR fluorophore cyanine-5 (Cy5)，is a Vemurafenib (HY-12057)-based inhibitor of BRAF. Vem-L-Cy5 targets to BRAFV600E，and also inhibits MEK phosphorylation. Vem-L-Cy5 has cell permeability，and inhibits cell growth of many types of cancer.
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Belvarafenib TFA
0 ImagesCat. No.: HY-109080ACAS No.: 2443966-84-3Synonyms: HM95573 TFA; GDC-5573 TFA; RG6185 TFA
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Cyclorasin 9A5 TFA
0 ImagesCat. No.: HY-P10051APurity: 99.57%Cyclorasin 9A5 TFA is an 11-residue cell-permeable cyclic peptide that orthosterically inhibits the Ras-Raf protein interaction with an IC50 of 120 nM.
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Regorafenib-d3
0 ImagesSynonyms: BAY 73-4506-d3Regorafenib-d3 (BAY 73-4506-d3) is a deuterium labeled Regorafenib (HY-10331). Regorafenib is a multi-targeted receptor tyrosine kinase inhibitor.
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(E/Z)-Locostatin
0 ImagesSynonyms: (E/Z)-UIC-1005(E/Z)-Locostatin ((E/Z)-UIC-1005) is a racemic of Locostatin. Locostatin (UIC-1005) is a potent RKIP inhibitor. Locostatin binds Raf kinase inhibitor RKIP protein and disrupts the interaction of RKIP with Raf-1 kinase and G protein-coupled receptor kinase 2. Locostatin inhibits cell proliferation and migration. Locostatin aggravates thioacetamide (HY-Y0698)-induced acute liver failure in mice .
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R18
0 ImagesCat. No.: HY-P1039CAS No.: 211364-78-2Synonyms: PHCVPRDLSWLDLEANMCLP
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Cyclorasin 9A5
0 ImagesCat. No.: HY-P10051CAS No.: 1782098-79-6Cyclorasin 9A5 is an 11-residue cell-permeable cyclic peptide that orthosterically inhibits the Ras-Raf protein interaction with an IC50 of 120 nM.
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Everafenib
0 ImagesEverafenib is a potent and blood-brain barrier (BBB) penetrant BRAF inhibitor, also inhibits MAPK signaling. Everafenib has inhibitory activity against a panel of V600EBRAF melanoma cell lines with IC50 values of 2-10 nM, which is better than Dabrafenib (HY-14660) and Vemurafenib (HY-12057). Everafenib has efficacy in an intracranial mouse model of metastatic melanoma.
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SB-590885 (Standard)
0 ImagesSB-590885 (Standard) is the analytical standard of SB-590885 (HY-10966). This product is intended for research and analytical applications. SB-590885 is a BRAF/c-Raf kinase inhibitor that selectively targets B-Raf, and it amplifies the ERK/MAPK signaling pathway in RAS-activated cells. SB-590885 effectively inhibits the malignant proliferation, transformation and tumorigenicity of oncogenic B-Raf cells; it also induces the proliferation of erythroid progenitor cells, delays their differentiation and promotes hemoglobin synthesis, thereby improving ineffective erythropoiesis and reducing apoptosis. SB-590885 exerts a synergistic effect with TGF-β inhibitors and glucocorticoids, significantly promoting the formation of erythroid colonies in cells from patients with Diamond-Blackfan anemia (DBA). SB-590885 is mainly used in relevant studies on DBA, cisplatin-induced myelosuppression-related anemia, and pan-cancers such as melanoma and colorectal cancer.
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Vemurafenib (Standard)
0 ImagesSynonyms: PLX4032 (Standard); RG7204 (Standard); RO5185426 (Standard)Vemurafenib (Standard) is the analytical standard of Vemurafenib. This product is intended for research and analytical applications. Vemurafenib (PLX4032) is a first-in-class, selective, potent inhibitor of B-RAF kinase, with IC50s of 31 and 48 nM for RAFV600E and c-RAF-1, respectively. Vemurafenib induces cell autophagy.
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Pan-RAF kinase inhibitor 1
0 ImagesCat. No.: HY-142452CAS No.: 2648838-76-8Pan-RAF kinase inhibitor 1 is a potent inhibitor of Pan-RAF kinase. Pan-RAF kinase inhibitor 1 regulates MAPK signaling by inhibiting RAF kinase, thereby exerting an effect on the proliferation of RAS-mutant tumor cells. Pan-RAF kinase inhibitor 1 has the potential for the research of cancer diseases (extracted from patent WO2021110141A1, compound 16B).
