In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4523-4523
Abstract:
Sorafenib, a small molecule kinase inhibitor, has been approved for renal carcinoma (RCC) and hepatocellular carcinoma (HCC) by FDA. Our data shows that sorafenib inhibits signal transducers and activators of transcription 3 activity and induces apoptosis in HCC cells. The major target is that Sorafenib enhances Src homology-2-containing protein tyrosine phosphatase-1 (SHP-1) activity, reduces the phosphorylation of STAT3 and subsequently reduces the STAT3-regulating protein, Mcl-1, survivin and cyclinD1. Therefore, we design and synthesize a series of sorafenib analogues which show the higher potency in inducing apoptosis and inhibiting phosphorylation of STAT3 than sorafenib. In addition, these agents have no inhibition of Raf and VEGFR in HCC cells. Therefore, the new agents provide a new concept that increasing SHP-1 activity along and synergizing with other therapeutic agents will be applicable in HCC therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4523. doi:10.1158/1538-7445.AM2011-4523
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-4523
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
