Abstract
Aberrant activation of Raf signaling pathway is frequently found in various human tumors, it has been considered as distinct and promising molecular target for cancer therapeutics. B-Raf is most attractive drug target out of three Raf isoforms (A-Raf, B-Raf and C-Raf) because it exhibits high kinase activity due to frequent mutations in human tumors. However, most recently, it has been reported that Raf isoforms show the cross-activation in the presence of specific B-Raf inhibitors, which brings about the paradoxical p-ERK activation as well as tumor promoting effect. According to these findings, it remains controversy whether pan-Raf kinase inhibitor is more valuable and promising rather than specific B-Raf inhibitor under certain conditions in terms of cancer therapeutics. In this short review, novel Raf kinase inhibitors undergoing clinical investigation are introduced. Moreover, the paradoxical p-ERK activation is discussed with specific B-Raf inhibitors, PLX4032/4720 compounds.
| Original language | English |
|---|---|
| Pages (from-to) | 605-615 |
| Number of pages | 11 |
| Journal | Archives of Pharmacal Research |
| Volume | 35 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2012 Apr 1 |
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Keywords
- Cancer
- Molecular-targeted inhibitor
- PLX4720/4032
- Raf kinase
- Sorafenib
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
- Organic Chemistry
Cite this
Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics. / Kim, Do Hee; Sim, Taebo.
In: Archives of Pharmacal Research, Vol. 35, No. 4, 01.04.2012, p. 605-615.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics
AU - Kim, Do Hee
AU - Sim, Taebo
PY - 2012/4/1
Y1 - 2012/4/1
N2 - Aberrant activation of Raf signaling pathway is frequently found in various human tumors, it has been considered as distinct and promising molecular target for cancer therapeutics. B-Raf is most attractive drug target out of three Raf isoforms (A-Raf, B-Raf and C-Raf) because it exhibits high kinase activity due to frequent mutations in human tumors. However, most recently, it has been reported that Raf isoforms show the cross-activation in the presence of specific B-Raf inhibitors, which brings about the paradoxical p-ERK activation as well as tumor promoting effect. According to these findings, it remains controversy whether pan-Raf kinase inhibitor is more valuable and promising rather than specific B-Raf inhibitor under certain conditions in terms of cancer therapeutics. In this short review, novel Raf kinase inhibitors undergoing clinical investigation are introduced. Moreover, the paradoxical p-ERK activation is discussed with specific B-Raf inhibitors, PLX4032/4720 compounds.
AB - Aberrant activation of Raf signaling pathway is frequently found in various human tumors, it has been considered as distinct and promising molecular target for cancer therapeutics. B-Raf is most attractive drug target out of three Raf isoforms (A-Raf, B-Raf and C-Raf) because it exhibits high kinase activity due to frequent mutations in human tumors. However, most recently, it has been reported that Raf isoforms show the cross-activation in the presence of specific B-Raf inhibitors, which brings about the paradoxical p-ERK activation as well as tumor promoting effect. According to these findings, it remains controversy whether pan-Raf kinase inhibitor is more valuable and promising rather than specific B-Raf inhibitor under certain conditions in terms of cancer therapeutics. In this short review, novel Raf kinase inhibitors undergoing clinical investigation are introduced. Moreover, the paradoxical p-ERK activation is discussed with specific B-Raf inhibitors, PLX4032/4720 compounds.
KW - Cancer
KW - Molecular-targeted inhibitor
KW - PLX4720/4032
KW - Raf kinase
KW - Sorafenib
UR - http://www.scopus.com/inward/record.url?scp=84862902308&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862902308&partnerID=8YFLogxK
U2 - 10.1007/s12272-012-0403-5
DO - 10.1007/s12272-012-0403-5
M3 - Article
C2 - 22553052
AN - SCOPUS:84862902308
VL - 35
SP - 605
EP - 615
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
SN - 0253-6269
IS - 4
ER -