Chemical Name : PCI-24781/CRA-02478/
CAS : 783355-60-2
Solubility:formulated in 30% HP-cyclodextrin in water
Storage:-20℃ 2 years
PCI-24781 (CRA-024781) is a novel broad spectrum hydroxamic acid-based inhibitor of histone deacetylase (HDAC) that shows antitumor activity in vitro and in vivo preclinically and is under evaluation in phase I clinical trials for cancer.PCI-24781 inhibited pure recombinant HDAC1 with a Ki of 0.007 Mmol/L, and also inhibited the other HDAC isozymes HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range.Antitumor activity of PCI-24781 was observed in all 10 tumor cell lines tested, with GI50% values ranging from 0.15 to 3.09 Amol/L.CRA-024781 parenterally administered to mice harboring HCT116 or DLD-1 colon tumor xenografts resulted in a statistically significant reduction in tumor growth at doses that were well tolerated as measured by body weight.
1. Bhalla S, Balasubramanian S, David K, Sirisawad M, Buggy J, Mauro L, Prachand S, Miller R, Gordon LI, Evens AM. PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res. 2009 May 15;15(10):3354-65. Epub 2009 May 5. 2. Lopez G, Liu J, Ren W, Wei W, Wang S, Lahat G, Zhu QS, Bornmann WG, McConkey DJ, Pollock RE, Lev DC. Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma. Clin Cancer Res. 2009 May 15;15(10):3472-83. Epub 2009 May 5. 3. Adimoolam S, Sirisawad M, Chen J, Thiemann P, Ford JM, Buggy JJ. HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7. Epub 2007 Nov 27. 4. Banuelos CA, Ban��th JP, MacPhail SH, Zhao J, Reitsema T, Olive PL. Radiosensitization by the histone deacetylase inhibitor PCI-24781. Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6816-26. 5. Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17.