Product Categories

Raf Serine/threonine-protein Kinase Raf

  • Compare Raf Inhibitors
  • Research Area

Raf Inhibitors (15)

water-soluble

Cat.No. Product Name Information Product Citations Customer Reviews
S1267 Vemurafenib (PLX4032, RG7204) Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM.
S1040 Sorafenib Tosylate Sorafenib Tosylate (Bay 43-9006) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.
S2807 Dabrafenib (GSK2118436) Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with IC50 of 0.8 nM, with 4- and 6-fold less potency against B-Raf(wt) and c-Raf, respectively. Phase 3.
S1152 PLX-4720 PLX4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf.
S2161 RAF265 (CHIR-265) RAF265 (CHIR-265) is a potent selective inhibitor of C-Raf/B-Raf/B-Raf V600E with IC50 of 3-60 nM, and exhibits potent inhibition on VEGFR2 phosphorylation with EC50 of 30 nM. Phase 2.
S2746 AZ 628 AZ628 is a new pan-Raf inhibitor for BRAF, BRAFV600E, and c-Raf-1 with IC50 of 105 nM, 34 nM and 29 nM, also inhibits VEGFR2, DDR2, Lyn, Flt1, FMS, etc.
S1104 GDC-0879 GDC-0879 is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM with activity against c-Raf as well; no inhibition known to other protein kinases.
S2220 SB590885 SB590885 is a potent B-Raf inhibitor with Ki of 0.16 nM, 11-fold greater selectivity for B-Raf over c-Raf, no inhibition to other human kinases.
S2872 GW5074 GW5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms is noted.
S2202 NVP-BHG712 NVP-BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM that discriminates between VEGFR and EphB4 inhibition; also shows activity against c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM, respectively.
Cat.No. Product Name Information Product Citations Customer Reviews
S8015 CEP-32496 CEP-32496 is a highly potent inhibitor of BRAF(V600E/WT) and c-Raf with Kd of 14 nM/36 nM and 39 nM, also potent to Abl-1, c-Kit, Ret, PDGFRβ and VEGFR2, respectively; insignificant affinity for MEK-1, MEK-2, ERK-1 and ERK-2. Phase 1/2.
S2720 ZM 336372 ZM 336372 is a potent and selective c-Raf inhibitor with IC50 of 70 nM, 10-fold selectivity over B-RAF, no inhibition to PKA/B/C, AMPK, p70S6, etc.
S2200 Raf265 derivative A derivative of Raf265, however, the effects of this derivative are not known.
S7001 PF-04880594 PF-04880594 is a RAF inhibitor for BRAF/BRAFV599E and c-RAF with IC50 of 0.19 nM/0.13 nM and 0.39 nM, >100-fold selectivity over CSNK1, JNK2/3 and p38.
S7121 MLN2480 MLN-2480 (BIIB-024) is a pan-Raf inhibitor.
Page:
  • 1
  • 2
All Raf Inhibitors

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]

References

[1] Roskoski, R. RAF protein-serine/threonine kinases: Structure and regulation. Biochem Biophys Res Commun. 2010;80: 624-637.
[2] Solit, DB and Nissan, MH. The “SWOT” of BRAF Inhibition in Melanoma: RAF Inhibitors, MEK Inhibitors or Both? Curr. Oncol. Rep. 2011;13: 479-487.

Tags: B-Raf inhibition | Raf inhibition | B-Raf mutation | B-Raf cancer | Raf tumor | Raf pathway | Raf inhibitor drugs | Raf activation | Raf targets | Raf activity | Raf phosphorylation | B-Raf assay | Raf kinase assay | B-Raf inhibitor clinical trial | B-Raf inhibitor drug | Raf inhibitor review