Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics

Do Hee Kim, Taebo Sim

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish
Pages (from-to)605-615
Number of pages11
JournalArchives of Pharmacal Research
Volume35
Issue number4
DOIs
Publication statusPublished - 2012 Apr 1

Fingerprint

raf Kinases
Chemical activation
Tumors
Molecules
Neoplasms
Protein Isoforms
Therapeutics
Phosphotransferases
Mutation
Pharmaceutical Preparations

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 journalArticle

Kim, Do Hee ; Sim, Taebo. / Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics. In: Archives of Pharmacal Research. 2012 ; Vol. 35, No. 4. pp. 605-615.
@article{a70eb7ea21ed4e83af106a1fd3bd9c77,
title = "Novel small molecule Raf kinase inhibitors for targeted cancer therapeutics",
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.",
keywords = "Cancer, Molecular-targeted inhibitor, PLX4720/4032, Raf kinase, Sorafenib",
author = "Kim, {Do Hee} and Taebo Sim",
year = "2012",
month = "4",
day = "1",
doi = "10.1007/s12272-012-0403-5",
language = "English",
volume = "35",
pages = "605--615",
journal = "Archives of Pharmacal Research",
issn = "0253-6269",
publisher = "Pharmaceutical Society of Korea",
number = "4",

}

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 -