Chloroquine

Endosomal acidification and autophagy inhibitor

Chloroquine is a lysosomotropic agent that was historically developed as an anti-malarial treatment. However, it has become a widely used inhibitor for studying autophagy and the role of endosomal acidification in cellular processes (i.e. intracellular TLR signaling). As a weak base, chloroquine passively diffuses into the acidic compartments of the cell, including endosomes, Golgi vesicles, and lysosomes, where it becomes protonated, trapping it within the organelle. This accumulation of chloroquine leads to an increase in the pH of the compartment and the inhibition of several enzymes that require an acidic pH for proper functioning. Thus, chloroquine prevents maturation and fusion of endosomes and lysosomes [1]. 

Chloroquine has an extensive range of biological effects and due to its well-studied toxicity profile is one of the only autophagy inhibitors approved for use in the clinic. Chloroquine impairs the replication of several viruses, including members of flaviviruses, retroviruses, and coronaviruses, by inhibiting the necessary endosome acidification upon endosomal-mediated viral entry and vesicle trafficking in the later stages of infection (i.e. through the ER-Golgi and exocytosis from the cell) [2,3]. Additionally, the accumulation of chloroquine in lymphocytes and macrophages decreases the production of pro-inflammatory cytokines, specifically TNF-α, and results in anti-inflammatory properties [2]. Thus, chloroquine is used routinely in the clinic for inflammatory conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) [4]. Finally, modulation of autophagy by chloroquine has been shown to have potential in delaying the onset and/or enhancing therapies for various pathologies such as cancer, chronic obstructive pulmonary disease (COPD), and inflammatory diseases. Specifically, it has been shown, in vitro and in vivo, that chloroquine has a detrimental effect on the basal autophagic flux by decreasing autophagosome-lysosome fusion due to impaired function of essential hydrolases [5].

Chloroquine provided by InvivoGen is for research use only. 

Key features of Chloroquine:

• Extensively used in the literature as an endosomal acidification and autophagy inhibitor 
• Inhibitory function validated in cellular assays
• Highly pure (> 98%) and absence of any bacterial contamination has been confirmed

References:

1. Ducharme, J. & Farinotti, R. 1996. Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements. Clin Pharmacokinet 31, 257-274.
2. Savarino, A. et al. 2003. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis 3, 722-727.
3. Wang, M. et al. 2020. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269-271.
4. Al-Bari, M.A. 2015. Chloroquine analogs in drug discovery: new directions of uses, mechanisms of actions, and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother 70, 1608-1621.

Specifications

Working concentration: 10 μM

CAS number: 50-63-5

Synoym: N4-(7-Chloro-4-quinolinyl)-N1,N1-dimethyl-1,4- pentanediamine diphosphate salt

Solubility: 50 mg/ml in water

Molecular weight: 515.86 g/mol

Quality control:

• Purity: ≥98% (UHPLC)
• The inhibitory activity has been validated using cellular assays.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ hTLR2 and HEK-Blue™ hTLR4 cells.

Contents

• 250 mg Chloroquine (diphosphate salt)

Chloroquine is shipped at room temperature.

Store at room temperature (15-25°C). Protect from light.

Product in powder form is stable for 6 months at room temperature when properly stored.

Details

Chemical structure of Chloroquine