试药MCC-478 (LY582563)对HBV的野株和拉米抗药型有效益

liver411

"研究显示它对拉米夫丁抗药在M552I, M552V和 L528M/M552V变异型有效益, 而且对野株型HBV的作用是拉米的20倍(0.027 microM)...;"

原文简摘:

Antimicrob Agents Chemother 2002 Aug;46(8):2602-5


[B]Novel Nucleoside Analogue MCC-478 (LY582563) Is Effective against Wild-Type or Lamivudine-Resistant Hepatitis B Virus. [/B]

Ono-Nita SK, Kato N, Shiratori Y, Carrilho FJ, Omata M.

Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo CEP 05403-000, Brazil.

The emergence of resistant hepatitis B virus (HBV) with the L528M mutation and/or the M552V and M552I mutations in the polymerase gene following long-term lamivudine treatment is becoming an important clinical problem. The aim of this study was to investigate the susceptibility of wild-type and lamivudine-resistant HBV to MCC-478 (LY582563), a novel nucleoside analogue derivative of phosphonomethoxyethyl purine. The susceptibility of wild-type HBV and lamivudine-resistant mutants (M552I, M552V, and L528M/M552V) to MCC-478 was examined by transient transfection of full-length HBV DNA into human hepatoma cells. HBV DNA replication was monitored by Southern blot hybridization, and the effective concentration required to reduce replication by 50% (EC(50)) was determined. The replicative intermediates of wild-type and lamivudine-resistant mutants were progressively diminished by treatment with increasing doses of MCC-478. The MCC-478 EC(50)s were 0.027
microM for wild-type HBV (about 20 times more efficient than lamivudine),
2.6 microM for M552I, 3.3 microM for M552V, and 2.0 microM for L528M/M552V. Wild-type HBV and lamivudine-resistant mutants are susceptible to MCC-478. MCC-478 appears to be a candidate for the treatment of HBV infection and exhibits potent activity against lamivudine-resistant HBV.

PMID: 12121939 [PubMed - in process]

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