Description |
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. |
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IC50 & Target |
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] |
In Vitro |
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]. |
In Vivo |
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]. |
References |
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Preparing Stock Solutions |
Please refer to the solubility information to select the appropriate solvent.
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Kinase Assay
[2] |
The stock solution (10 mM) of GC376 is prepared in DMSO and further diluted in assay buffer. The final concentrations of DMSO in the assay did not exceed 1.5% (vol/vol). The 3CLpro from NV, MD145 or MNV-1 are incubated with various concentrations (0.01 to 50 µM) of GC376 in 25 µL of assay buffer for 30 min at 37 °C. Following incubation, 25 µL of assay buffer containing substrate is added, and the mixtures are incubated in a 96-well black plate at 37 °C for 60 min. The fluorescence signals are detected using an excitation and emission wavelength of 490 and 520 nm on a fluorescence microplate reader. The RFU are calculated for each well, and the dose-dependent FRET inhibition curves are fitted with variable slope (four parameters) using GraphPad Prism software in order to determine the IC50 values of GC376[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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References |
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Molecular Weight |
507.53 |
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Formula |
C₂₁H₃₀N₃NaO₈S |
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CAS No. |
1416992-39-6 |
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Storage |
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Shipping | Room temperature in continental US; may vary elsewhere |
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Solvent & Solubility |
DMSO; In Vivo: GC376 is dissolved in 10% ethanol and 90% PEG-400.
* "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">1> |
Purity: 99.96%
COA (94 KB) HNMR (1113 KB) RP-HPLC (109 KB)
Handling Instructions (1252 KB)-
[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.
[2]. Takahashi D, et al. Structural and inhibitor studies of norovirus 3C-like proteases. Virus Res. 2013 Dec 26;178(2):437-44.
[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.
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westblot蛋白免疫印迹实验跑小分子蛋白(15kd)条带一直是波浪状,有人说是胶的问题,可同时跑了36kd蛋白,条带是直的,有人说是要恒流跑,电压不要太大,我的转膜条件是50v,50min,请教各位大神指点,万分感谢!!!
如题,之前没做过药代,老师给了一个600+Da的五肽,想测下药代动参数,看文献推荐上述两种方法,但是不知道选哪种更好,lcms前处理会不会影响小肽。
求助各位前辈,我最近在合成的化合物水溶性很好,非常好,以至于可以随便溶解在水里,它的六氟磷酸盐也可以随意溶解在水里(大于50uM),细胞成像实验显示它根本进不去细胞,求问有没有啥方法包裹一下让它进去?我搜了一下文献,感觉多数是把脂溶性特别好的东西包裹一下弄进去的,也许是搜索姿势不对没找到我需要的答案,**点拨啊!!!
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有机的是有机化合物的简称,它指的是含碳化合物.
但是,有四大类常见物质一般不作为有机物处理:
1、碳的氧化物,如CO和CO2.
2、碳酸及其盐,如CaCO3.
3、金属碳化物,如CaC2.
4、拟卤素及其化合物,如(CN)2与KSCN.
水的化学式为H2O,它不含有碳元素,故不是有机物.
但若所描述的水不是化学意义的水,而是自然界存在的天然水,那么,水中会溶有一定量的有机物.