Bucillamine

Bucillamine is a drug used in the treatment of rheumatoid arthritis developed from tiopronin.

Bucillamine

Mechanism of action

The pharmaceutical drug activity is mediated by the two thiol groups that the molecule contains.

Use in rheumatoid arthritis

Bucillamine is used in the treatment of rheumatoid arthritis in Japan and South Korea for over 30 years.

Chemical structure

• It is a cysteine derivative with 2 thiol groups.
• It is 16-fold more potent than acetylcysteine (NAC) as a thiol donor in vivo
• It has potential to prevent acute lung injury during influenza infection.
• Bucillamine has also been shown to prevent oxidative and reperfusion injury in heart and liver tissues.

Benefits compared to Acetylcystein

• Bucillamine has both proven safety and proven mechanism of action similar to that of NAC, but with much higher potency, mitigating the previous obstacles to using thiols therapeutically.

Studies for use in COVID-19

• It is believed that reactive oxygen species (ROS) are involved in acute lung injury during nCov-19 infection, possibly justifying the investigation of bucillamine as an intervention for COVID-19.
• On July 31st, 2020, the U.S. Food & Drug Administration (FDA) has approved Revive Therapeutics Ltd. to proceed with a randomized, double-blind, placebo-controlled confirmatory Phase 3 clinical trial to evaluate the safety and efficacy of Bucillamine in patients with mild-moderate COVID-19.

COVID-19 and bucillamine clinital trials

• Bucillamine trial in COVID-19

Other studies

• In Phase I human studies in normal volunteers, bucillamine at doses up to 25 mg/kg/h i.v. for 3 h elicited no serious toxicity.

Proposed use

On the basis of pharmacokinetic analyses studies, it is proposed that bucillamine, infused at i.v. doses > or =10 mg/kg/h for 3 h to humans could be expected to be therapeutically effective in myocardial infarction, organ transplantation and other acute inflammatory syndromes.