Belumosudil metabolites and uses thereof in the treatment of chronic graft-versus-host disease
Inventors
Schueller, Olivier • Patel, Jeegar P.
Assignees
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Publication Number
US-11952369-B2
Publication Date
2024-04-09
Expiration Date
Abstract
The present disclosure provides metabolites of belumosudil and uses of the metabolites in of treating patients with ROCK2-mediated diseases including cGVHD.
Core Innovation
The disclosure describes belumosudil as a ROCK2 inhibitor used for chronic graft-versus-host disease (cGVHD) and reports human metabolism of belumosudil, including newly identified metabolites. It identifies KD025m1 and KD025m2 as metabolites of belumosudil, with KD025m1 reported as minor active and KD025m2 reported as major.
The previously unknown metabolites reported include belumosudil glucuronide and O-dealkylated belumosudil sulfate. The disclosure also reports monohydroxy belumosudil and belumosudil diol, with these metabolites found in feces, and provides metabolite exposure relationships, including that KD025m2 is approximately 15–20% of parent and KD025m1 is less than 5% of parent.
The disclosure states a human metabolic pathway for use in preparing medicaments/protocols and describes that isolated or synthesized metabolites and pharmaceutically acceptable salts can be used to treat ROCK2-mediated diseases. The text specifically includes autoimmune disorders such as cGVHD among the listed indications, and associates ROCK2-mediated diseases with other listed autoimmune/fibrotic conditions.
Claims Coverage
The partial claims provide one independent claim and one dependent claim. The inventive coverage centers on isolated or synthesized human metabolites of belumosudil, specifically a glucuronide and an O-dealkylated sulfate, including pharmaceutically acceptable salts, with dependent coverage directed to a pharmaceutical composition including a carrier.
Isolated or synthesized belumosudil glucuronide or O-dealkylated belumosudil sulfate
An isolated or synthesized belumosudil glucuronide or O-dealkylated belumosudil sulfate, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition including the claimed metabolite and a carrier
A pharmaceutical composition comprising the compound of the independent claim and a pharmaceutically acceptable carrier.
Overall, the claims cover isolated or synthesized metabolites of the ROCK2 inhibitor belumosudil—belumosudil glucuronide and O-dealkylated belumosudil sulfate, and pharmaceutically acceptable salts—and a pharmaceutical composition including the claimed metabolite with a pharmaceutically acceptable carrier.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of ROCK2-mediated diseases including autoimmune disorders such as chronic graft-versus-host disease (cGVHD).
Treatment of other listed autoimmune/fibrotic conditions associated with ROCK2-mediated diseases.
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