Table 1.

Chemical structures, aminopeptidase inhibition, and inhibition of tumor cell growth by CHR-2797

A
AminopeptidaseCHR-2797CHR-79888Bestatin
Embedded Image Embedded Image Embedded Image
PuSA150850350
LTA4 hydrolase>10,0008200
Aminopeptidase N220190300
PILSAP>5,000>5,000>5,000
Aminopeptidase B>1,000>1,0001,000
LAP100304
MetAP-2>30,000>30,000
B
Cell lineTumor typeIC50 (nmol/L)K-RasPTENTP53
U-937Histiocytic lymphoma10mutmut
HL-60Promyelocytic leukemia30wtwtmut
KG-1Acute myelogenous leukemia15wtwtmut
RPMI 8226Myeloma330mutwtmut
MEG-01Megakaryoblastic leukemia400wtwtwt
HNT-34Acute myelogenous leukemia35
AML-193Acute monocytic leukemia770wtwtwt
KU812Chronic myelogenous leukemia100wtwtwt
MV-4-11Biphenotypic myelomonocytic leukemia305wtwtwt
GDM-1Myelomonoblastic leukemia15wtwtwt
HEL 92.1.7Erythroleukemia10,000
CCRF-CEMAcute lymphoblastic leukemia3,800mutmutmut
MOLT-4Acute lymphoblastic leukemia1,450wtmutmut
HuT 78Cutaneous T cell lymphoma>10,000wtwtmut
Jurkat E6-1Acute T cell leukemia>10,000mutmut
  • NOTE: (A) Aminopeptidase assays were conducted in the presence of the compounds shown. IC50 values (nmol/L) represent the mean of two to three independent experiments involving at least six concentrations of drug per experiment.

    (B) Inhibition of the proliferation of human cancer cell lines was measured by [3H]thymidine incorporation. Plates were formatted so that there were six replicates for each concentration of compound to be tested. The data presented are the means of at least two separate experiments.

    Abbreviations: wt, wild type; mut, mutant.