Fragment-based de novo design of a cystathionine γ-lyase selective inhibitor blocking hydrogen sulfide production

More about Open Access at the Crick


Hydrogen sulfide is an essential catabolite that intervenes in the pathophysiology of several diseases from hypertension to stroke, diabetes and pancreatitis. It is endogenously synthesized mainly by two pyridoxal-5'-phosphate-dependent enzymes involved in L-cysteine metabolism: cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). Research in this field is currently impaired by the lack of pharmacological tools such as selective enzymatic inhibitors that could target specifically only one of these pathways. We used a novel approach based on a hybrid method that includes drug design, synthetic biology, metabolomics and pharmacological assays to rationally design a new inhibitor selective for the CSE enzyme. The identification of this compound opens new frontiers towards a better understanding of the role of CSE over CBS in the pathophysiology of diseases where a role for the HS pathway has been proposed and the development of new lead compounds that could target the CSE enzyme.

Journal details

Volume 6
Pages 34398
Available online
Publication date

Crick labs/facilities

Crick authors

Crick First author
Crick Corresponding author