MEFLOQUINE

Mefloquine (Mefloquin), an orally active and potent quinoline antimalarial agent, is an anti-SARS-CoV-2 entry inhibitor. Mefloquine is also a K+ channel (KvQT1/minK) antagonist with an IC50 of ~1 μM. Mefloquine can be used for malaria, systemic lupus erythematosus and cancer research[1][2][3].

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ROS

Signaling Pathways >> Anti-infection >> SARS-CoV

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Inflammation/Immunology

Research Areas >> Metabolic Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Mefloquine selectively inhibits prostate cancer (PCa) cell growth with an IC50 of ~10 μM. Mefloquine also induces hyperpolarization of the mitochondrial membrane potential (MMP), as well as ROS generation[2]. Mefloquine (10 μM)-mediated ROS simultaneously downregulated Akt phosphorylation and activated ERK, JNK and AMPK signaling in PC3 cells[2]. Mefloquine shows higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 of 1.28 μM, IC90 of 2.31 μM, and IC99 of 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibits viral entry after viral attachment to the target cell[3].

Mefloquine (5 mg/kg; i.p.; daily; 14 days) reverses the lower vertebral cancellous bone volume and bone formation; and has modest effects on cortical bone volume, thickness, and moment of inertia in old mice[4].

[1]. Kang J, et al. Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK andHERG. J Pharmacol Exp Ther. 2001 Oct;299(1):290-6.

[2]. Yan KH, et al. Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling. Oncol Lett. 2013 May;5(5):1541-1545.

[3]. Kaho Shionoya, et al. Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro. Front Microbiol. 2021 Apr 30;12:651403.

[4]. Rafael Pacheco-Costa, et al. Reversal of loss of bone mass in old mice treated with mefloquine. Bone. 2018 Sep;114:22-31.

MOLECULAR FORMULA :

C17-H16-F6-N2-O

MOLECULAR WEIGHT :

378.35

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

25 mg/kg/5W-I

TOXIC EFFECTS :

Behavioral - muscle weakness Musculoskeletal - joints Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 123,894,1995