Belumosudil, sold under the brand name Rezurock among others, is a medication used for the treatment of chronic graft versus host disease (cGvHD).It is in the class of drugs known as  serine/threonine kinase inhibitors. Specifically, it is an inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2; ROCK-II). Belumosudil binds to and inhibits the  serine/threonine kinase activity of ROCK2. This inhibits ROCK2-mediated signaling pathways which play major roles in pro- and anti-inflammatory immune cell responses. A genomic study in human primary cells demonstrated that the drug also has effects on oxidative phosphorylation, WNT signaling, angiogenesis, and KRAS signaling.The most common side effects include infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension.Belumosudil was approved for medical use in the United States in July 2021. Medical uses
Belumosudil is indicated for the treatment of people aged 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. History
Originally developed by Surface Logix, Inc, belumosudil was later acquired by Kadmon Corporation. By July 2020, the drug completed Phase II clinical studies for cGvHD, IPF, and psoriasis.cGvHD is a complication that can follow  allogeneic stem cell or hematopoietic stem cell transplantation  where the transplanted cells (graft) attack healthy cells (host). This causes inflammation and fibrosis in multiple tissues. Two cytokines controlled by the ROCK2 signaling pathway,  IL-17 and IL-21, have a major role in the cGvHD response.
To minimize the risk of CRS and to offset some of the minor side effects patient experience, glucocorticoids (such as methylprednisolone), acetaminophen, and diphenhydramine are given before the infusion.Other adverse effects include leucopenia, as well as an increased risk for severe infections and malignancies typical of immunosuppressive therapies. Neurological side effects like aseptic meningitis and encephalopathy have been observed. Possibly, they are also caused by the T cell activation.Repeated application can result in tachyphylaxis (reduced effectiveness) due to the formation of anti-mouse antibodies in the patient, which accelerates elimination of the drug. It can also lead to an anaphylactic reaction against the mouse protein, which may be difficult to distinguish from a CRS. Contraindications
Except under special circumstances, the drug is contraindicated for patients with an allergy against mouse proteins, as well as patients with uncompensated heart failure, uncontrolled arterial hypertension or epilepsy. It should not be used during pregnancy or lactation. Etymology
Muromonab-CD3 was developed before the WHO nomenclature of monoclonal antibodies took effect, and consequently its name does not follow this convention. Instead, it is a contraction from "murine monoclonal antibody targeting CD3". == References ==