Belumosudil
[CAS# 911417-87-3]

Identification

• Classification: Biochemical >> Inhibitor >> Cell cycle >> ROCK inhibitor
• Name: Belumosudil
• Synonyms: 2-[3-[4-(1H-indazol-5-ylamino)quinazolin-2-yl]phenoxy]-N-propan-2-ylacetamide
• Molecular Formula: C₂₆H₂₄N₆O₂
• Molecular Weight: 452.51
• CAS Registry Number: 911417-87-3
• SMILES: CC(C)NC(=O)COC1=CC=CC(=C1)C2=NC3=CC=CC=C3C(=N2)NC4=CC5=C(C=C4)NN=C5

Properties

• Solubility: Insoluble (2.2E^-4 g/L) (25 °C), Calc.^*, 17 mg/mL (DMSO) (Expl.)
• Density: 1.318±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.705, Calc.^*
• Boiling Point: 682.6±55.0 °C (760 mmHg), Calc.^*
• Flash Point: 366.6±31.5 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302
• Safety Statements: P280-P305+P351+P338

Discovery and Applications

Belumosudil is a selective inhibitor of the enzyme rho-associated coiled-coil kinase 2 (ROCK2), which plays a significant role in various cellular processes, including cell migration, proliferation, and survival. This chemical substance was developed as a potential treatment for autoimmune diseases and certain cancers. Its discovery emerged from ongoing research into targeting specific molecular pathways involved in immune regulation and inflammatory responses.

Belumosudil was developed by Kadmon Corporation and is primarily used for the treatment of chronic graft-versus-host disease (cGVHD), a condition that can occur following stem cell or bone marrow transplants. In cGVHD, donor immune cells attack the recipient’s tissues, leading to inflammation and organ damage. The drug was approved by the U.S. Food and Drug Administration (FDA) in 2021 as a therapeutic option for this condition. By inhibiting ROCK2, belumosudil helps to modulate the immune system, reducing the activity of T-cells that contribute to the inflammatory process in cGVHD.

One of the key applications of belumosudil is in patients with cGVHD who have not responded well to other treatments, such as corticosteroids or immunosuppressive therapies. The drug works by targeting the intracellular signaling pathways that drive T-cell activation and tissue damage, ultimately leading to a reduction in disease severity. Its efficacy has been demonstrated in clinical trials, where patients experienced improvements in symptoms and reductions in disease progression.

In addition to its use in cGVHD, belumosudil is also being explored for its potential application in other immune-mediated diseases, such as systemic lupus erythematosus (SLE) and idiopathic pulmonary fibrosis (IPF). Ongoing research aims to further understand its mechanisms of action and potential benefits in treating a range of autoimmune and inflammatory conditions.

The development of belumosudil represents a significant advancement in the treatment of cGVHD and other autoimmune diseases. It highlights the growing trend of targeted therapies that specifically modulate immune responses to treat conditions that were previously difficult to manage. The success of belumosudil in clinical settings offers new hope for patients with chronic and severe inflammatory diseases, providing a promising alternative to more traditional therapies.

References

2021. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood, 138(22).
DOI: 10.1182/blood.2021012021

2024. A phase II study of belumosudil for chronic graft-versus-host disease in patients who failed at least one line of systemic therapy in China. BMC Medicine, 22.
DOI: 10.1186/s12916-024-03348-5

2023. Cutaneous Squamous-Cell Carcinoma after Treatment with Ruxolitinib or Belumosudil. The New England journal of medicine, 389(2).
DOI: 10.1056/nejmc2304157