Synthesis of pochoxime prodrugs as potent HSP90 inhibitors.
Pochoximes are potent inhibitors of heat shock protein 90 (HSP90) based on the radicicol pharmacophores. Herein we present a pharmacokinetics and pharmacodynamics evaluation of this compound series as well as a phosphate prodrug strategy to facilitate formulation and improve oral bioavailability.
Wang
Cuihua
C
Institute de Science et d'Ingénierie Supramoleculaires, Université de Strasbourg, Strasbourg, France.
Barluenga
Sofia
S
Koripelly
Girish K
GK
Fontaine
Jean-Gonzague
JG
Chen
Ruihong
R
Yu
Jin-Chen
JC
Shen
Xiaodong
X
Chabala
John C
JC
Heck
James V
JV
Rubenstein
Allan
A
Winssinger
Nicolas
N
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018942:Macrolides / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D018942:Macrolides; D011355:Prodrugs; C035359:monorden