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Raf Serine/threonine-protein Kinase Raf

Research Area
Research Area

Cat.No.	Product Name	Solubility (25°C)
S1267	Vemurafenib (PLX4032)	<1 mg/mL	98 mg/mL	<1 mg/mL
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1152	PLX-4720	<1 mg/mL	83 mg/mL	<1 mg/mL
S2807	Dabrafenib (GSK2118436)	<1 mg/mL	30 mg/mL	2 mg/mL
S1104	GDC-0879	<1 mg/mL	67 mg/mL	5 mg/mL
S2872	GW5074	<1 mg/mL	104 mg/mL	<1 mg/mL
S1178	Regorafenib (BAY 73-4506)	<1 mg/mL	97 mg/mL	<1 mg/mL
S2161	RAF265 (CHIR-265)	<1 mg/mL	104 mg/mL	33 mg/mL
S2746	AZ628	<1 mg/mL	90 mg/mL	<1 mg/mL
S2720	ZM 336372	<1 mg/mL	78 mg/mL	2 mg/mL
S2220	SB590885	<1 mg/mL	5 mg/mL	<1 mg/mL
S2202	NVP-BHG712	<1 mg/mL	101 mg/mL	3 mg/mL
S2200	Raf265 derivative	<1 mg/mL	101 mg/mL	101 mg/mL
S8015	CEP-32496	<1 mg/mL	9 mg/mL	<1 mg/mL

Raf Inhibitors (15)
water-soluble

Cat.No.	Product Name	Information	Product Citations
S1267	Vemurafenib (PLX4032)	PLX4032 (Vemurafenib, RG7204, Zelboraf, RO5185426) is a novel and potent inhibitor of B-Raf^V600E with IC50 of 31 nM.	Nature, 2012, 483(7387), 100-103 Cell, 2012, 151(5):937-50 Nat Med, 2012, ahead of print
S1040	Sorafenib (Nexavar)	Sorafenib Tosylate (Bay 43-9006, Nexavar) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.	Blood, 2012, 120(19):4104-15 Cell Death Differ, 2012, 19(12):2029-39 Clin Cancer Res, 2011, 17(24):7595-604
S1152	PLX-4720	PLX-4720 is a potent and selective inhibitor of B-Raf^V600E and c-Raf-1^Y340D/Y341D with IC50 of 13 nM and 6.7 nM, respectively.	Nature, 2012, 483(7387), 100-103 Genes Dev, 2012, 26(10):1055-69 Proc Natl Acad Sci U S A, 2011, 108(15), 6067-6072
S2807	Dabrafenib (GSK2118436)	Dabrafenib (GSK2118436) is a potent ATP-competitive inhibitor of B-Raf, B-Raf^V600E and c-Raf with IC50 of 3.2 nM, 0.8 nM and 5.0 nM, respectively.
S1104	GDC-0879	GDC-0879 is a novel potent, selective B-Raf inhibitor for B-Raf^V600E with IC50 of 0.13 nM.	Proc Natl Acad Sci U S A, 2011, 108(15), 6067-6072 Cell Death Differ, 2012, 19(12):2029-39 Sci Signal, 2012, 5(224):rs4
S7001	PF-04880594	PF-04880594 is a RAF inhibitor for BRAF and c-RAF with IC50 of 0.19 nM and 0.39 nM, respectively.
S2872	GW5074	GW5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM.	Hepatology, 2012, ahead of print
S1178	Regorafenib (BAY 73-4506)	Regorafenib (BAY 73-4506, Fluoro-Sorafenib) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.	Cancer Discov, 2013, ahead of print
S2161	RAF265 (CHIR-265)	RAF265 (CHIR-265) is a selective and potent inhibitor of B-Raf and VEGFR2 with IC50 of 3-60 nM and EC50 of 30 nM, respectively.
S2746	AZ628	AZ628 is a potent inhibitor for wild-type CRAF and BRAF^V600E with IC50 of 29 nM and 34 nM, respectively.

Cat.No.	Product Name	Information	Product Citations
S2720	ZM 336372	ZM 336372 is a potent and selective c-Raf inhibitor with IC50 of 70 nM.
S2220	SB590885	SB590885 is a potent B-Raf inhibitor with K_i of 0.16 nM.	Mol Cell Proteomics, 2012, 11(9):745-57
S2202	NVP-BHG712	NVP-BHG712 is a specific inhibitor of c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM and also inhibits EphB4 and VEGFR2 with ED50 of 25 nM and 4.2 μM, respectively.
S2200	Raf265 derivative	A derivative of Raf265. But the effects of this derivative is not known.
S8015	CEP-32496	CEP-32496 is a RAF inhibitor for BRAF(V600E), BRAF(WT), c-Raf, Abl-1 and CSF-1R with IC50 of 14 nM, 36 nM, 39 nM, 3 nM and 9 nM, respectively.

Inhibitory Selectivity
Solubility

Cat.No.	Product Name	Solubility (25°C)
S1267	Vemurafenib (PLX4032)	<1 mg/mL	98 mg/mL	<1 mg/mL
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1152	PLX-4720	<1 mg/mL	83 mg/mL	<1 mg/mL
S2807	Dabrafenib (GSK2118436)	<1 mg/mL	30 mg/mL	2 mg/mL
S1104	GDC-0879	<1 mg/mL	67 mg/mL	5 mg/mL
S2872	GW5074	<1 mg/mL	104 mg/mL	<1 mg/mL
S1178	Regorafenib (BAY 73-4506)	<1 mg/mL	97 mg/mL	<1 mg/mL
S2161	RAF265 (CHIR-265)	<1 mg/mL	104 mg/mL	33 mg/mL
S2746	AZ628	<1 mg/mL	90 mg/mL	<1 mg/mL
S2720	ZM 336372	<1 mg/mL	78 mg/mL	2 mg/mL
S2220	SB590885	<1 mg/mL	5 mg/mL	<1 mg/mL
S2202	NVP-BHG712	<1 mg/mL	101 mg/mL	3 mg/mL
S2200	Raf265 derivative	<1 mg/mL	101 mg/mL	101 mg/mL
S8015	CEP-32496	<1 mg/mL	9 mg/mL	<1 mg/mL

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.

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Raf Serine/threonine-protein Kinase Raf

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Raf Inhibitors (15)
water-soluble

References

Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1267	Vemurafenib (PLX4032)	<1 mg/mL	98 mg/mL	<1 mg/mL
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1152	PLX-4720	<1 mg/mL	83 mg/mL	<1 mg/mL
S2807	Dabrafenib (GSK2118436)	<1 mg/mL	30 mg/mL	2 mg/mL
S1104	GDC-0879	<1 mg/mL	67 mg/mL	5 mg/mL
S2872	GW5074	<1 mg/mL	104 mg/mL	<1 mg/mL
S1178	Regorafenib (BAY 73-4506)	<1 mg/mL	97 mg/mL	<1 mg/mL
S2161	RAF265 (CHIR-265)	<1 mg/mL	104 mg/mL	33 mg/mL
S2746	AZ628	<1 mg/mL	90 mg/mL	<1 mg/mL
S2720	ZM 336372	<1 mg/mL	78 mg/mL	2 mg/mL
S2220	SB590885	<1 mg/mL	5 mg/mL	<1 mg/mL
S2202	NVP-BHG712	<1 mg/mL	101 mg/mL	3 mg/mL
S2200	Raf265 derivative	<1 mg/mL	101 mg/mL	101 mg/mL
S8015	CEP-32496	<1 mg/mL	9 mg/mL	<1 mg/mL

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Raf Serine/threonine-protein Kinase Raf

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Raf Inhibitors (15)water-soluble

References

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Raf Inhibitors (15)
water-soluble