A high-performance liquid chromatography method for the quantification of cysmethynil, an inhibitor of isoprenylcysteine carboxylmethyl transferase, in mouse plasma.
Cysmethynil, a newly identified small molecule inhibitor of isoprenylcysteine carboxylmethyl transferase (Icmt) is involved in the post-translational modification of CaaX proteins. Cysmethynil causes cell death in many human cancer cells in vitro, and inhibits tumor growth in the xenograft mouse model in vivo. A HPLC method for the quantification of cysmethynil in mouse plasma was developed and validated. The lower limit of quantification of this method was 0.01microg/ml. Inter- and intra-day variability ranged from 0.38-8.5% and accuracy was between 86% and 98%. This sensitive method was used to quantify cysmethynil in plasma of mice after intraperitoneal dosing for preliminary pharmacokinetic studies.
Wang
Mei
M
Program of Cancer Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169547, Singapore.
Khoo
Yok Moi
YM
Zhou
Jin
J
Casey
Patrick
P
Lee
How Sung
HS
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D005615:Freezing; D007211:Indoles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors* / Q000097:blood*; D015203:Reproducibility of Results; D013696:Temperature; D013997:Time Factors
D004791:Enzyme Inhibitors; D007211:Indoles; C530692:cysmethynil; D011496:Protein Methyltransferases