B-raf plays crucial roles in MAPK signaling pathway, ErbB signaling pathway, Insulin signaling pathway and mTOR signaling pathway which have effect on cell survival, growth and differentiation. RAF can be regulated by RAS and PKC. [show the full text]
Raf Inhibitors
Productos selectivos de isoformas
| Nº Cat. | Nombre del producto | Información | Citas de uso del producto | Validaciones del producto |
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| S2807 | Dabrafenib (GSK2118436) | Dabrafenib es un inhibidor específico de la BRAFV600E mutante con una IC50 de 0,7 nM en ensayos sin células, con una potencia 7 y 9 veces menor contra B-Raf(wt) y c-Raf, respectivamente. |
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| S7842 | LY3009120 | LY3009120 (DP-4978) es un potente inhibidor pan-Raf con IC50 de 44 nM, 31-47 nM y 42 nM para A-raf, B-Raf y C-Raf en células A375, respectivamente. Este compuesto induce la autophagy. Fase 1. |
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| S1267 | PLX4032 (Vemurafenib) | Vemurafenib (PLX4032, RG7204, RO5185426) es un nuevo y potente inhibidor de B-RafV600E con una IC50 de 31 nM en un ensayo sin células. 10 veces más selectivo para B-RafV600E que para B-Raf de tipo salvaje en ensayos enzimáticos y la selectividad celular puede superar las 100 veces. Vemurafenib (PLX4032, RG7204) induce la Autophagy. |
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| E1649 | Exarafenib (KIN-2787) | Exarafenib (KIN-002787, KIN-2787, RAF/KIN_2787) es un inhibidor selectivo de pan-RAF disponible por vía oral. Exarafenib es eficaz en cánceres dependientes de RAF, incluidas todas las clases de alteraciones de BRAF. Exarafenib suprime la señalización MAPK en líneas celulares de melanoma dependientes de RAF. KIN-2787 exhibe una potencia nanomolar a picomolar baja contra RAF1, BRAF y ARAF con un IC50 de 0,06-3,46 nM con actividad mínima hacia quinasas no RAF. | ||
| S7397 | Sorafenib (BAY 43-9006) | Sorafenib es un inhibidor multiquinasa de Raf-1 y B-Raf con una IC50 de 6 nM y 22 nM en ensayos libres de células, respectivamente. Sorafenib inhibe VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 y c-KIT con una IC50 de 90 nM, 20 nM, 57 nM, 59 nM y 68 nM, respectivamente. Sorafenib induce autophagy y apoptosis y activa ferroptosis con actividad antitumoral. |
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| S1104 | GDC-0879 | GDC-0879 (AR-00341677) es un inhibidor de B-Raf nuevo, potente y selectivo con una IC50 de 0,13 nM en células A375 y Colo205 con actividad también contra c-Raf; no se conoce inhibición de otras proteínas quinasas. |
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| S7170 | Avutometinib (Ro5126766, CH5126766) | Avutometinib(RO5126766,CH5126766,VS 6766, CKI-27, R-7304, RG-7304) es un inhibidor dual de RAF/MEK con IC50 de 8,2 nM, 19 nM, 56 nM y 160 nM para BRAF V600E, BRAF, CRAF y MEK1, respectivamente. Fase 1. |
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| S1040 | Sorafenib Tosylate (BAY 43-9006) | Sorafenib Tosylate es un inhibidor multiquinasa de Raf-1 y B-Raf con una IC50 de 6 nM y 22 nM en ensayos libres de células, respectivamente. Sorafenib Tosylate inhibe VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 y c-KIT con una IC50 de 90 nM, 20 nM, 57 nM, 59 nM y 68 nM, respectivamente. Sorafenib Tosylate induce la autophagy y la apoptosis y activa la ferroptosis con actividad antitumoral. |
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| S1152 | PLX-4720 | PLX4720 es un inhibidor potente y selectivo de B-RafV600E con una IC50 de 13 nM en un ensayo sin células, igualmente potente que c-Raf-1 (mutaciones Y340D y Y341D), con una selectividad 10 veces mayor para B-RafV600E que para B-Raf de tipo salvaje. |
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| S5069 | Dabrafenib Mesylate | Dabrafenib Mesylate (GSK2118436) es la sal mesilato de dabrafenib, un inhibidor oralmente biodisponible de la proteína B-raf (BRAF) con CI50 de 0,8 nM, 3,2 nM y 5 nM para B-Raf (V600E), B-Raf (WT) y C-Raf, respectivamente. |
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RAF kinase signaling is highlighted in the RAS-RAF-MEK-ERK signal transduction cascade. Activated RAS kinase signaling results in the activation of RAF proteins. Following these events, MEK1 and MEK2 dual specificity protein kinases become phosphorylated and activated. It should be noted that RAF kinases display restricted substrate specificity for these MEK enzymes. The RAF family of protein-serine/threonine kinases comprise of A-RAF, B-RAF, and C-RAF oncogenes originally discovered in the early 1980s. RAF family proteins function as six dimeric members, either in homo- and heterodimer formation. Since there are four RAS members, the total number of RAS-RAF interactions is equivalent to twenty-four. And downstream, with two MEK members available the total number of interactions between RAF-MEK constituents is twelve.[1]
All RAF kinases share three conserved regions (CR): CR1, CR2, and CR3. CR1 consists of cysteine-rich domain (binds to two zinc ions) and a RAS-binding domain. These properties facilitate CR1 interaction with RAS and phospholipids in the membrane. CR2, is a serine/threonine rich domain that facilitates the binding of regulatory protein 14-3-3 upon phosphorylation – this result in inactivation. At the C-terminus is the protein kinase domain, CR3, which contains a downstream stimulatory 14-3-3 binding site. Regulating RAF kinase activity are a number of protein-protein interactions, phosphorylation, dephosphorylation and conformational changes. In their inactivated state, most RAF proteins are found in the cytosol.[1]
It was not until 2002, that B-RAF mutations were noted in cancer cells lines. Most notably, B-RAF has been associated with melanomas and papillary thyroid, ovarian, and colorectal tumors. And to a lesser degree cancers of the lung, pancreas, and bladder have also been found to have aberrant B-RAF activity. Consequently, since B-RAF mutations are involved in several different cancer types it is believed that B-RAF functions as an oncogene driver. In clinical trials, the first RAF inhibitor was Bayer’s Sorafenib (Nexavar). The compound was found to be effective in restricting tumor activity in renal cell carcinoma and hepatocellular cancers and is currently in use for these indications. Recently, PLX4032 was discovered to be a highly selective RAF inhibitor (Roche) and is currently in advanced clinical trials for testing against melanomas.[2]
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