328543-09-5 Usage
Biological Activity
ag-14361 is a selective inhibitor of parp-1 with ki50 valueparp1 is a member of prap family and plays an important role in many cellular processes, such as dna repair, programmed cell death. it has been revealed that parp1 is abnormally expressed in a variety of cancers and many parp inhibitors have been developed as the anti-tumor drugs [1] [2] [3, 4].ag-14361 is a potent parp-1 inhibitor. when exposed hr and brca2-defective cells and parental cells to ag-14361, hr-defective cells were hypersensitive to the ag-14361 even at non-cytotoxic concentrations and lacking brca2 made the cells more sensitive to ag-14361 [5]. in human k562 cells, ag14361 treatment for 16 hours resulted in significant (~2-fold) potentiation of camptothecin-induced growth inhibition (gi50, 16 hours, camptothecin + ag14361 2.4 ± 0.1 nmol/l), cytotoxicity (lc50, camptothecin + ag14361 2.77 ± 0.55 nmol/l) and dna single-strand breaks via inhibiting parp-1 [1]. when tested with mmr-proficient (hct-ch3, a2780, and cp70-ch3) and mmr-deficient (hct116, cp70, and cp70-ch2) cells, mmr-proficient cells were more sensitivity to temozolomide compared with mmr-deficient cells after exposed to ag-14361 which inhibited parp1 activity [2].in mouse model xenografted with brca2-deficient and brca-2 proficient tumor cells, brca2 deficiency group had more response even completely regressed tumor compared with brca-2 proficient group when treated with ag-14361 [5].
references
[1]. smith, l.m., et al., the novel poly(adp-ribose) polymerase inhibitor, ag14361, sensitizes cells to topoisomerase i poisons by increasing the persistence of dna strand breaks. clin cancer res, 2005. 11(23): p. 8449-57.[2]. curtin, n.j., et al., novel poly(adp-ribose) polymerase-1 inhibitor, ag14361, restores sensitivity to temozolomide in mismatch repair-deficient cells. clin cancer res, 2004. 10(3): p. 881-9.[3]. calabrese, c.r., et al., anticancer chemosensitization and radiosensitization by the novel poly(adp-ribose) polymerase-1 inhibitor ag14361. j natl cancer inst, 2004. 96(1): p. 56-67.[4]. veuger, s.j., et al., radiosensitization and dna repair inhibition by the combined use of novel inhibitors of dna-dependent protein kinase and poly(adp-ribose) polymerase-1. cancer res, 2003. 63(18): p. 6008-15.[5]. kyle, s., et al., exploiting the achilles heel of cancer: the therapeutic potential of poly(adp-ribose) polymerase inhibitors in brca2-defective cancer. br j radiol, 2008. 81 spec no 1: p. s6-11.
Check Digit Verification of cas no
The CAS Registry Mumber 328543-09-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,2,8,5,4 and 3 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 328543-09:
(8*3)+(7*2)+(6*8)+(5*5)+(4*4)+(3*3)+(2*0)+(1*9)=145
145 % 10 = 5
So 328543-09-5 is a valid CAS Registry Number.
328543-09-5Relevant articles and documents
Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors
Skalitzky, Donald J.,Marakovits, Joseph T.,Maegley, Karen A.,Ekker, Anne,Yu, Xiao-Hong,Hostomsky, Zdenek,Webber, Stephen E.,Eastman, Brian W.,Almassy, Robert,Li, Jianke,Curtin, Nicola J.,Newell, David R.,Calvert, A. Hilary,Griffin, Roger J.,Golding, Bernard T.
, p. 210 - 213 (2007/10/03)
Novel tricyclic benzimidazole carboxamide poly-(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhi
