Preclinical anticancer activity of cryptophycin-8.
Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.
Corbett
T H
TH
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Valeriote
F A
FA
Demchik
L
L
Polin
L
L
Panchapor
C
C
Pugh
S
S
White
K
K
Knight
J
J
Jones
J
J
Jones
L
L
LoRusso
P
P
Foster
B
B
Wiegand
R A
RA
Lisow
L
L
Golakoti
T
T
Heltzel
C E
CE
Ogino
J
J
Patterson
G M
GM
Moore
R E
RE
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D047630:Depsipeptides; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007769:Lactams / Q000627:therapeutic use* / Q000633:toxicity; D007783:Lactones / Q000627:therapeutic use* / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; C107304:cryptophycin 8