Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25075010
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Benzimidazole analogs as potent hypoxia inducible factor inhibitors: synthesis,
biological evaluation, and profiling drug-like properties
#MMPMID25075010
Chen J
; Wang J
; Schwab LP
; Park KT
; Seagroves TN
; Jennings LK
; Miller DD
; Li W
Anticancer Res
2014[Aug]; 34
(8
): 3891-904
PMID25075010
show ga
AIM: To develop potent HIF-1? inhibitors for potential treatment of cancer.
MATERIALS AND METHODS: Chemical synthesis, HIF-luciferase assay, cytotoxic assay,
platelet aggregation assay, western blot analysis, quantitative real-time PCR,
aqueous solubility, protein binding, metabolic stability, and metabolic pathways.
RESULTS: Thirteen novel benzimidazole analogs were synthesized. Compounds 3a and
3k showed the highest anti-HIF-1? activity. They are significantly more effective
than YC-1 in the suppression of HIF-1? protein expression based on western blot
assay. They show comparable potency in inhibition of cancer cell migration. They
are less potent in the inhibition of platelet aggregation. 3k had the most
favorable drug-like properties, including long half-life in human liver
microsomes, medium protein binding level and reasonable aqueous solubility.
CONCLUSION: The potent anti-HIF-1? activity and favorable drug-like properties of
compound 3k suggest that it may hold great potential as an adjuvant therapy for
cancer treatment through repression of HIF-1? protein expression.
free
free
free
