In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 825-825
Abstract:
Poly (ADP-ribose) Polymerase (PARP) plays a critical role in DNA repair processes. Small molecule inhibitors of PARP for the treatment of cancer are currently being investigated either single agents or in combination therapy with other DNA damaging agents. Based on recent published data, PARP inhibitors have shown promising results as a powerful therapeutic anticancer agents, especially in tumors deficient in BRCA-1or BRCA-2 function. In this study, we present a novel synthetic inhibitor of poly (ADP-ribose) polymerase (PARP) for their anti-tumor activity in various types of tumor xenograft model. Among new synthetic PARP inhibitors, JPI-283 shows synergistic effects in vitro cell cytotoxicity with DNA damaging agent such as Temozolomide(TMZ), SN-38, and CDDP. Also, JPI-283 represents a potential anticancer activity in BRCA-1 and BRCA-2 mutant cells as a single agent. In tumor xenograft model studies, the combination of JPI-283 with TMZ by oral dosing results in more than 60-70% tumor growth inhibition rate, compared to the control group in CAPAN-1, U87MG, MDA-MB-468 and SW620 tumor xenograft model. In addition, the combination of JPI-283 with CDDP shows superior antitumor activity compared to that of AZD2281 with CDDP in MDA-MB468 triple negative breast tumor xenograft model. The pharmacokinetics of JPI-283 in mouse and rat shows over 50% bioavailability. These findings suggest that JPI-283 would be an attractive therapeutic candidate for the treatment of cancer including DNA repair deficient cancer. Citation Format: Ji-Seon Park, Jang-Hyun Kim, Kwang-Woo Cheon, Bo-Young Cho, Kang-Jeon Kim, Han-Chang Lee, Young-Cheol Kim, Hyung-Chan Oh, Hyun-Ho Lee, Jeong-Min Kim. The development of a novel PARP inhibitor with potent antitumor activity in various tumor xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstra ct nr 825. doi:10.1158/1538-7445.AM2014-825
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-825
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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