SPI-112 is a potent, selective and competitive SHP2 (PTPN11) inhibitor with IC50s of 1 μM, 18.3 μM and 14.5 μM for SHP2, protein tyrosine phosphatase (PTP) and PTP1B, respectively[1][2].
SPI-112 has a polar -NO2 or a negatively charged -COOH group and has no detectable cellular activity, suggesting that SPI-112 is not cell permeable[1]. In surface plasmon resonance (SPR) binding assay, SPI-112 displays a 1:1 stoichiometric binding kinetics to SHP2 with a kinetic constant KD of 1.30 µM. Enzyme kinetic data obtained with SPI-112 are best fitted with the competitive inhibition model (Ki of 0.8 µM), suggesting that SPI-112 interacts with the catalytic site of SHP2[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
468.46
Formula
C22H17FN4O5S
CAS 号
1051387-90-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Chen L, et al. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112. Biochem Pharmacol. 2010 Sep 15;80(6):801-10.
[2]. Lawrence HR, et al. Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J Med Chem. 2008 Aug 28;51(16):4948-56.
Ebselen (SPI-1005), a glutathione peroxidase mimetic, is a potent voltage-dependent calcium channel (VDCC) blocker[1][2]. Ebselen potently inhibits Mpro (IC50=0.67 μM) and COVID-19 virus (EC50=4.67 μM)[3].Ebselen is an inhibitor of HIV-1 capsid CTD dimerization. Ebselen, an organoselenium compound, can permeate the blood-brain barrier and has anti-inflammatory, antioxidant and anticancer activity[4][5].
Ebselen (SPI-1005; 0.4-100 μM; 20-24 hours) shows strong antiviral effects at a concentration of 10 μM treatment in COVID-19 virus infected Vero cells. Ebsele covalently binds to C145 of the catalytic dyad in COVID-19 virus Mpro[3]. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process[4]. Ebselen permeates the blood-brain barrier and inhibits endogenous inositol monophosphatase in mouse brain. Ebselen inhibits inositol monophosphatase (IMPase)[5]. Ebselen inhibits QSOX1 enzymatic activity and suppresses invasion of pancreatic, renal cancer cell lines[6].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
RT-PCR[3]
Cell Line:
COVID-19 virus infected Vero cells
Concentration:
0.4, 1.2, 3.7, 11.1, 33.3, 100 μM
Incubation Time:
20-24 hours
Result:
Showed strong antiviral effects at a concentration of 10 μM treatment.
体内研究 (In Vivo)
Ebselen (5, 10 mg/kg; IP) decreases 5-HT2 agonist-induced head twitches in a dose-dependent manner[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
20-25 g 10-12 week old male C57Bl6 mice[5]
Dosage:
5, 10 mg/kg
Administration:
IP
Result:
Decreased 5-HT2 agonist-induced head twitches in a dose-dependent manner.
Clinical Trial
分子量
274.18
Formula
C13H9NOSe
CAS 号
60940-34-3
中文名称
依布硒；依布硒林
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Liang Q, et al. Electrical Stimulation Degenerated Cochlear Synapses Through Oxidative Stress in NeonatalCochlear Explants. Front Neurosci. 2019 Oct 14;13:1073.
[2]. H Sies, et al. Ebselen, a Selenoorganic Compound as Glutathione Peroxidase Mimic
[3]. Jin Z, et al. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9.
[4]. Thenin-Houssier S, et al. Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2195-208.
[5]. Singh N, et al. A safe lithium mimetic for bipolar disorder. Nat Commun. 2013;4:1332. doi: 10.1038/ncomms2320.
[6]. Hanavan PD, et al. Ebselen inhibits QSOX1 enzymatic activity and suppresses invasion of pancreatic and renal cancer cell lines. Oncotarget. 2015 Jul 30;6(21):18418-28.
