[1]. Said A, et al. Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23 release by monocyte-derived Langerhans-like cells. J Immunol. 2014 Dec 15;193(12):6135-43.
[2]. Tuomela J, et al. Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer. Oncol Lett. 2013 Dec;6(6):1665-1672.
[3]. Mohamed FE, et al. Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2014 Jul 2. doi: 10.1111/liv.12626.
每孔将5微升2%L-α-磷脂酰胆碱在十二烷中的溶液沉积在96孔板的膜上。将AT791(10μM),E6446(10μM),硫酸羟氯喹(40μM)或氯喹(40μM)加入pH 5.5缓冲液(50 mM NaAce,15 mM NaCl)或pH 7.4缓冲液中的两个隔室之一中(50mM KPO 4,150mM NaCl),将板在37℃温育。第二天,定量两个室中的化合物浓度。在该实验的一个变体中,向两个室中加入5μMAT791或E6446,其中一个含有pH 5.5缓冲液,另一个含有pH 7.4缓冲液。监测两室之间化合物的重新分布8小时[2]。
[1]. Manzo C, et al. Psychomotor Agitation Following Treatment with Hydroxychloroquine. Drug Saf Case Rep. 2017 Dec;4(1):6.
[2]. Lamphier M, et al. Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. Mol Pharmacol. 2014 Mar;85(3):429-40
Chloroquine is an antimalarial and anti-inflammatory agent widely used to treat malaria and rheumatoid arthritis. Chloroquine is an autophagy and toll-like receptors (TLRs) inhibitor. Chloroquine is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro (EC50=1.13 μM)[1-4].
In Vitro
Chloroquine (CHQ, 20 μM) inhibits IL-12p70 release and reduces Th1-priming capacity of activated human monocyte-derived Langerhans-like cells (MoLC). Chloroquine (20 μM) enhances IL-1–induced IL-23 secretion in MoLC and subsequently increases IL-17A release by primed CD4+ T cells[1]. Chloroquine (25 μM) suppresses MMP-9 mRNA expression in normoxia and hypoxia in parental MDA-MB-231 cells. Chloroquine has cell-, dose- and hypoxia-dependent effects on MMP-2, MMP-9 and MMP-13 mRNA expression[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly reduces HuH7 cell proliferation in vitro[3].Chloroquine (0.01-100 μM; 48?hours) potently blocked virus infection (vero E6 cells infected with SARS-CoV-2) at low-micromolar concentration (EC50=1.13?μM). Chloroquine blocks virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV[4].
In Vivo
TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly inhibits tumour growth in the mouse xenograft model. HCC development in the DEN/NMOR rat model is also significantly inhibited by Chloroquine[3].Chloroquine (80 mg/kg, i.p.) does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in the orthotopic mouse model[2].
SMILES
CCN(CC)CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl
靶点
Autophagy, SARS-CoV, Toll-like Receptor (TLR), HIV
数据来源文献
[1]. Said A, et al. Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23 release by monocyte-derived Langerhans-like cells. J Immunol. 2014 Dec 15;193(12):6135-43. [2]. Tuomela J, et al. Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer. Oncol Lett. 2013 Dec;6(6):1665-1672. [3]. Mohamed FE, et al. Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2014 Jul 2. doi: 10.1111/liv.12626. [4]. Colson P, et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4):105932.