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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Dabrafenib-d9
0 ImagesCat. No.: HY-14660SCAS No.: 1423119-98-5Synonyms: GSK2118436A-d9; GSK2118436-d9
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Anticancer agent 124
0 ImagesCat. No.: HY-108887CAS No.: 1884226-20-3Anticancer agent 124 is an orally active, highly selective and potent pan RAF inhibitor. Anticancer agent 124 inhibits MAPK signalling in BRAF V600E, NRAS and KRAS mutant tumor cells.
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PF-0419789
0 ImagesCat. No.: HY-11043CAS No.: 950525-20-9PF-0419789 is a BRAF (V600E) inhibitor that can be used to study BRAF V600 mutant solid tumors.
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PHI-501
0 ImagesCat. No.: HY-153858CAS No.: 2470433-36-2PHI-501 is a dual inhibitor targeting RAF/DDR. PHI-501 exhibits significant anti-proliferative effects in melanoma cell lines and significantly inhibits the colony formation of drug-resistant cells. PHI-501 strongly inhibits ERK and AKT phosphorylation. PHI-501 downregulates the gene sets in drug-resistant cells of TNFA-NFKB, IL6-JAK-STAT3, and KRAS signaling pathways as well as the epithelial-mesenchymal transition (EMT) signaling pathways. PHI-501 demonstrates significant anti-tumor effects in the SK-MEL3DR xenograft model. PHI-501 can be used for research on the problem of drug resistance in melanoma.
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ML786 dihydrochloride
0 ImagesCat. No.: HY-14979ACAS No.: 1237536-18-3ML786 dihydrochloride is a potent and orally bioavailable Raf inhibitor, with IC50s of 2.1, 4.2, and 2.5 nM for V600EΔB-Raf, wt B-Raf, and C-Raf, respectively. ML786 dihydrochloride also inhibits Abl-1, DDR2, EPHA2, KDR, and RET (IC50=<0.5, 7.0, 11, 6.2, 0.8 nM). ML786 dihydrochloride can be used for the research of cancers.
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ISIS 5132 sodium
0 ImagesCat. No.: HY-153490ASynonyms: CGP 69846A sodium; ISIS 9271 sodiumISIS 5132 sodium is a 20-base phosphorothioate oligonucleotide that specifically down-regulates c-raf expression.
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HDB-1
0 ImagesHDB-1 is a selective inhibitor of the P2Y14 receptor (P2Y14R) with an IC50 of 26 pM. HDB-1 shows no significant inhibition on P2Y1R, P2Y2R, P2Y4R, P2Y6R, and P2Y12R. HDB-1 blocks the activation of hepatic stellate cells (HSC) by inhibiting the PKA/Raf1/MEK/ERK signaling pathway mediated by P2Y14R, thereby alleviating the core pathological process of liver fibrosis. HDB-1 can be used for the study of liver fibrosis.
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Antitumor agent-60
0 ImagesCat. No.: HY-146432CAS No.: 865784-65-2Antitumor agent-60 (compound 20) is a potent antitumor agent, targeting RAS-RAF signaling pathway and binding to CRAF with a Kd value of 3.93 μM. Antitumor agent-60 induces apoptosis by blocking cell cycle at G2/M phase. Antitumor agent-60 enhances the level of p53 and ROS. Antitumor agent-60 causes oval and irregular nucleus in cancer cells. Antitumor agent-60 can suppress the growth of tumor to some extent in A549 xenograft model.
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Rafoxanide (Standard)
0 ImagesRafoxanide (Standard) is the analytical standard of Rafoxanide. This product is intended for research and analytical applications. Rafoxanide is a poent, orally active halogenated salicylaniline agent with antiparasitic activity. Rafoxanide interferes with energy metabolism in trematodes by uncoupling oxidative phosphorylation. Rafoxanide is also found to be a potent inhibitor of the BRAF V600E mutant protein, which is important in colorectal cancer. Rafoxanide can be used for the control of infestation with Hemonchus species or Fasciola species in sheep and cattle as well as Oestrus ovis in sheep. Rafoxanide can also be used for cancer research.
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SB-699393
0 ImagesCat. No.: HY-123799CAS No.: 502638-39-3B-699393 (Compound 17) is a BRAF inhibitor (Kd = 7.2 nM) that can cross the blood-brain barrier. SB-699393 can be used for research on stroke.
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Avutometinib potassium
0 ImagesCat. No.: HY-18652ACAS No.: 946128-90-1Synonyms: Ro 5126766 potassium; CH5126766 potassiumAvutometinib (CH5126766) (potassium) is a RAF/MEK clamp that potently inhibits RAF/MEK kinase activity and induces dominant negative RAF-MEK complexes preventing phosphorylation of MEK by ARAF, BRAF and CRAF. Avutometinib (potassium) shows anti-proliferative potency across tumor cell lines carrying KRAS mutations including PDAC cell lines. Avutometinib (potassium) induces tumor inhibition and increases survival in a KRAS/p53 pancreatic cancer mouse model. Avutometinib (potassium) is promising for research of low-grade-serous-ovarian-carcinoma (LGSOC), ovarian cancer and pancreatic ductal adenocarcinoma (PDAC).
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LSN3074753
0 ImagesCat. No.: HY-164492CAS No.: 1455031-68-1LSN3074753, an analog of LY3009120 (HY-12558), is a pan-RAF and Raf dimer inhibitor. LSN3074753 demonstrates activity against tumor cells with MAPK pathway activation driven by BRAF monomer or RAF dimers including BRAF- or KRAS-mutant colorectal cancer. LSN3074753 combined with Cetuximab (HY-P9905) shows additive and synergistic effects for colorectal cancer PDX models, particularly those with KRAS or BRAF mutation.
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SB-682330A
0 ImagesCat. No.: HY-141868CAS No.: 502498-66-0SB-682330A is a Raf kinase inhibitor.
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Vemurafenib-d7
0 ImagesCat. No.: HY-12057S1CAS No.: 1365986-73-7Synonyms: PLX4032-d7; RG7204-d7; RO5185426-d7
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Raf1 Mouse Pre-designed siRNA Set A
0 ImagesCat. No.: HY-RS11620Raf1 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Raf1 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
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Debromohymenialdisine
0 ImagesCat. No.: HY-113632CAS No.: 75593-17-8Synonyms: 10Z-DebromohymenialdisineDebromohymenialdisine (10Z-Debromohymenialdisine) is a pyrrole alkaloid. Debromohymenialdisine has moderate inhibitory activity with an IC50 value of 881 nM in the initial Raf/MEK-1/MAPK signaling cascade assay. Debromohymenialdisine can be used for the research of proliferation and differentiation.
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B-Raf IN 17
0 ImagesCat. No.: HY-158027B-Raf IN 17 (Compound 8e) is a potent and orally active type II multi-kinase inhibitor. B-Raf IN 17 exhibits potent cellular-level suppression of BRAFWT, VEGFR-2, and FGFR-1 in A375 cell line, with IC50 values of 0.02, 0.18 and 1.65 μM, respectively. B-Raf IN 17 can be used for the research of cancer.
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Raf1 Rat Pre-designed siRNA Set A
0 ImagesCat. No.: HY-RS11621Raf1 Rat Pre-designed siRNA Set A contains three designed siRNAs for Raf1 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
