GC376 sodium 

GC376 is a 3CLpro inhibitor; inhibits the replication of viruses TGEV, FIPV and PTV with IC₅₀ values of 0.15, 0.2 and 0.15 μM, respectively.

IC50: 0.15 μM (TGEV), 0.2 μM (FIPV), 0.15 μM (PTV), 0.15 μM (229E), 1.1 μM (MHV), 5.3 μM (MNV-1), 0.6 μM (BCV)^[1]

GC376 covalently binds to Cys 139, Cys 147, and Cys 144 of NV 3CLpro, PV 3Cpro, and TGEV 3CLpro, respectively. GC376 is significantly effective against caliciviruses (NV and MNV-1), coronaviruses (TGEV, FIPV, MHV, 229E, and BCV), and picornaviruses (HRVs 18, 51, and 68, EV71, and PTV), with nanomolar or low micromolar IC₅₀s, except for FCV and HAV. Interestingly, FCV is less sensitive to GC376, with IC₅₀ of 35 μM. GC376 shows no or weak effectiveness against the replication of HAV in cells^[1]. Proteases from NV, MD145 or MNV-1 are inhibited by GC376 with a similar potency. The IC₅₀ values of GC376 against 3CLpro from NV, MD145, and MNV-1 are comparable among tested viruses^[2]. GC376 effectively inhibits the replication of NPI52-resistant viruses in cell culture as wild-type viruses, indicating that the mutation does not confer cross-resistance to GC376^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

GC376 exhibits favorable bioavailability and safety in cats. GC376 is rapidly absorbed after s.c. administration and the peak plasma level is reached within 2 hr after injection. The mean plasma drug concentrations remains above the 50% effective concentration (EC₅₀) value of the aldehyde form of GC376 (8 ng/mL) for 18 hrs post injection. Virus infected cats shows improvement in attitude and resolution of fever. The profound absolute lymphopenia observed in all cats prior to antiviral treatment also returns to normal before the next blood testing one week later^[3]. Nineteen of 20 cats treated with GC376 regain outward health within 2 weeks of initial treatment. However, disease signs recur 1-7 weeks after primary treatment and relapses and new cases are ultimately treated for a minimum of 12 weeks^[4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

507.53

C₂₁H₃₀N₃NaO₈S

1416992-39-6

固体

Off-white to yellow

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

• [1]. Kim Y, et al. Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronaviruses. J Virol. 2012 Nov;86(21):11754-62.  [Content Brief]

  [2]. Takahashi D, et al. Structural and inhibitor studies of norovirus 3C-like proteases. Virus Res. 2013 Dec 26;178(2):437-44.  [Content Brief]

  [3]. Yunjeong Kim, et al. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor. PLoS Pathog. 2016 Mar 30;12(3):e1005531.  [Content Brief]

  [4]. Pedersen NC, et al. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J Feline Med Surg. 2017 Sep 1:1098612X17729626.  [Content Brief]