Guangzhou Academy of biological treatment of leukemia drug research for new breakthroughs
Small molecule inhibitor of Bcr-Abl Imatinib has been a great success in the clinical treatment of chronic myeloid leukemia (CML) and other diseases. Bcr-Abl mutations induced drug resistance has become an important issue in today's medical oncology. Second-generation drug Nilotinib and Dasatinib only to overcome the resistance caused by mutations in some genes, and Bcr-AblT315I the highest incidence of drug-resistant mutations invalid. The ponatinib December 2012 to overcome the Bcr-AblT315I resistance has just been approved by the FDA listed, but the P-Loop area mutations on the Bcr-AblE255K / V, etc. ineffective.
Recently, the Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health, Dr. Ding Ke led the team to successfully design and synthesis of aryl alkynes and triazole benzamide two types of small molecule inhibitors of Bcr-Abl after nearly four years of technical research. Compounds in a variety of kinases, cell and animal models can effectively overcome the problem of resistance the Bcr-AblT315I mutations induced. Which compounds GZD824 can pM IC50 values suppression the Bcr - AblWT and Bcr-AblT315I of resistant mutants kinase activity (respectively 0.34 and 0.68 nm), and the P-loop mutations (E255K / V). Compound in a variety of cell and animal models exhibit excellent anti-tumor activity (IC50 against the CML K562, Ku812 tumor cells 0.2-10nm; for Family the Bcr-AblT315I mutants Ba/F3 cells IC50 approximately 7Nm; in completely inhibit tumor growth the 1.0-20.0mg/kg/day oral dose) the and better safety indicators and excellent pharmacokinetic properties (rat oral bioavailability of approximately 48.7%; vivo half-life T1 / 2 of approximately 8-10 hours). Currently GZD824 have been identified as candidate drugs, the specification of ongoing pre-clinical Evaluation.
Guangzhou Academy of biological treatment of leukemia drug research for new breakthroughs
ReplyDeleteSmall molecule inhibitor of Bcr-Abl Imatinib has been a great success in the clinical treatment of chronic myeloid leukemia (CML) and other diseases. Bcr-Abl mutations induced drug resistance has become an important issue in today's medical oncology. Second-generation drug Nilotinib and Dasatinib only to overcome the resistance caused by mutations in some genes, and Bcr-AblT315I the highest incidence of drug-resistant mutations invalid. The ponatinib December 2012 to overcome the Bcr-AblT315I resistance has just been approved by the FDA listed, but the P-Loop area mutations on the Bcr-AblE255K / V, etc. ineffective.
Recently, the Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health, Dr. Ding Ke led the team to successfully design and synthesis of aryl alkynes and triazole benzamide two types of small molecule inhibitors of Bcr-Abl after nearly four years of technical research. Compounds in a variety of kinases, cell and animal models can effectively overcome the problem of resistance the Bcr-AblT315I mutations induced. Which compounds GZD824 can pM IC50 values suppression the Bcr - AblWT and Bcr-AblT315I of resistant mutants kinase activity (respectively 0.34 and 0.68 nm), and the P-loop mutations (E255K / V). Compound in a variety of cell and animal models exhibit excellent anti-tumor activity (IC50 against the CML K562, Ku812 tumor cells 0.2-10nm; for Family the Bcr-AblT315I mutants Ba/F3 cells IC50 approximately 7Nm; in completely inhibit tumor growth the 1.0-20.0mg/kg/day oral dose) the and better safety indicators and excellent pharmacokinetic properties (rat oral bioavailability of approximately 48.7%; vivo half-life T1 / 2 of approximately 8-10 hours). Currently GZD824 have been identified as candidate drugs, the specification of ongoing pre-clinical Evaluation.
Medchemexpress Can provide the above product,its website:www.medchemexpress.com
Tandutinib
KW-2449
Quizartinib
AST 487
Linifanib
Canertinib
Canertinib dihydrochloride
CP-724714 (E-Double bond)
2-Methoxyestradiol
GSK1904529A