Chloroquine(氯喹)

Chloroquine 是一种广泛用于疟疾和类风湿性关节炎的抗炎药物。Chloroquine 是 autophagy 和 toll-like receptors (TLRs) 的抑制剂。Chloroquine 有效抑制 SARS-CoV-2 (COVID-19) 感染 (EC50=1.13 μM)。

CAS：54-05-7
分子式：C18H26ClN3
分子量：319.87
纯度：＞98%
存储：Store at -20°C

Background:

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][2][3][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 (0.01-100μM; 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：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].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].

参考文献：

[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.

[5]. Savarino A, et al. The anti-HIV-1 activity of chloroquine. J Clin Virol. 2001;20(3):131-135.