| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T60405 | ||||
| Target Name | mRNA of RAF proto-oncogene serine/threonine-protein kinase | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | 5-(4-hydroxy-2,6-dimethylstyryl)nicotinic acid | Drug Info | IC50 = 400 nM | [528356] | |
| ZM-336372 | Drug Info | IC50 = 31 nM | [529039] | ||
| L-790070 | Drug Info | IC50 = 810 nM | [529561] | ||
| DEBROMOHYMENIALDISINE | Drug Info | IC50 = 881 nM | [526243] | ||
| GW-5074 | Drug Info | IC50 = 11 nM | [526991] | ||
| The Effect of Target Knockout, Knockdown or Genetic Variations | We find that the levels of RAF-1 and BRAF proteins and RAF kinase activity are increased in h uMan GBM samples. We confirm the importance of this finding by demonstrating a causal role for a constitutively active Raf-1 mutant in glioma formation in mice. Specifically, we find that activated Raf-1 cooperates with Arf loss or Akt activation to generate gliomas similar to activated KRas under the same conditions. Our study suggests that the oncogenic effect of KRas in glioma formation may be transduced at least in part through Raf signaling and that therapeutic targeting ofthis pathway may be beneficial in glioma treatment | [528356] | |||
| References | |||||
| Ref 528356 | Bioorg Med Chem Lett. 2006 Oct 15;16(20):5378-83. Epub 2006 Aug 4.Aza-stilbenes as potent and selective c-RAF inhibitors. | ||||
| Ref 529039 | Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. | ||||
| Ref 529561 | J Med Chem. 2008 Jul 24;51(14):4122-49. Epub 2008 Jun 26.Design, synthesis, and biological evaluation of novel Tri- and tetrasubstituted imidazoles as highly potent and specific ATP-mimetic inhibitors of p38 MAP kinase: focus on optimized interactions with the enzyme's surface-exposed front region. | ||||
| Ref 526243 | J Med Chem. 2002 Jan 17;45(2):529-32.Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). | ||||
| Ref 526991 | Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. | ||||
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