"目录号: HY-13986
Cell Cycle/DNA DamageAnti-infection-
Merimepodib 是次黄嘌呤核苷磷酸脱氢酶 (Inosine monophosphate dehydrogenase) 的非竞争性抑制剂。
Nucleoside Antimetabolite/AnalogHBV
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生物活性
Description
Merimepodib is a novel noncompetitive inhibitor ofIMPDH (Inosine monophosphate dehydrogenase).
In Vitro
VX-497 has antiproliferative effect on lymphoid and keratinocyte cells. The antiproliferative effect of VX-497 in cells is reversed within 48 h of its removal[1]. VX-497 has intermediate antiviral activity against a second group of viruses, which includes HSV-1, parainfluenza-3 virus, BVDV, VEEV, and dengue virus, with IC50s ranging from 6 to 19 μM. VX-497 is 100-fold more potent, with an IC50of 380 nM and a corresponding CC50of 5.2 μM, for a therapeutic index of 14. The antiviral activity of VX-497 in HepG2.2.2.15 cells is reversed threefold by the addition of guanosine[2].
In Vivo
Oral administration of VX-497 inhibits the primary IgM antibody response in a dose-dependent manner, with an ED50value of appr 30-35 mg/kg in mice. Single daily dosing of VX-497 is observed to be as effective as twice-daily dosing in this model of immune activation[1]. GVHD developed in the vehicle-treated allografted F1 mice and treatment with VX-497 improved all manifestations of the disease significantly. The 2.9-fold increase in spleen weight in allografted animals is reduced to a 1.6-fold increase in the VX-497-treated mice. Serum IFN-gamma levels are increased 54-fold in the vehicle group while there is a 7.4-fold increase in VX-497-treated animals[3].
Clinical Trial
NCT00088504
Vertex Pharmaceuticals Incorporated
Hepatitis C-Hepatitis
July 2004
Phase 2
NCT02904564
Clinica Dermatologica Arbache ltda
Photosensitivity Disorders
August 2016
Phase 4
NCT00935051
University Hospital, Grenoble
Diabetic Foot Ulcer
May 2009
Early Phase 1
NCT03194204
Assiut University
Rheumatoid Arthritis
October 1, 2017
NCT02893085
CHU de Reims
Cholangiocarcinoma, Cancer of the Head of the Pancreas
September 2015
NCT02883894
CHU de Reims
Bullous Pemphigoid
November 2009
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References
[1].Jain J, et al. VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37.
[2].Markland W, et al. Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon. Antimicrob Agents Chemother. 2000 Apr;44(4):859-66.
[3].Decker CJ, et al. The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice. Drugs Exp Clin Res. 2001;27(3):89-95.