The Effect of a New Immunosuppressive Drug, Brequinar Sodium, on Heart, Liver, and Kidney Allograft Rejection in the Rat

The design and development of an immunosuppressive drug, mycophenolate mofetil

“…It has potent antiproliferative effects on lymphocytes and prevents the rejection of heart, liver and kidney allografts in rats [20]. When BQR was administered to humans with cancer, limiting side effects included myelosuppression, especially thrombocytopenia, and mucositis.…”

Crosstalk between Nucleotide Synthesis Pathways with Cellular Immunity in Constraining Hepatitis E Virus Replication

“…Both BQR and LFM are immunosuppressive agents, although whether the mechanism of action is solely via pyrimidine inhibition remains controversial and unclear (44)(45)(46). The efficacy of BQR against graft rejection has been investigated extensively in preclinical models (47)(48)(49), and LFM has been proposed as an off-label immunosuppressive therapy in bone marrow (11) and renal (50) transplantation. In addition, DHODH inhibitors have been explored as treatments of other diseases, including malaria, autoimmune and inflammatory dis- eases, cancer, rheumatoid arthritis, and psoriasis (51)(52)(53)(54)(55).…”

Anti-arthritic effects of KF20444, a new immunosuppressive compound inhibiting dihydroorotate dehydrogenase, on rat collagen-induced arthritis

“…(6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H-benzo [6,7] cyclohepta [1,2-b] quinoline-8-carboxylic acid) was synthesized as one of a variety of derivatives of brequinar sodium (NSC368390; DuP 785). KF20444 exhibited an anti-proliferative activity against both T cells (phytohemagglutinin stimulation, IC 50 = 92 nM) and B cells (LPS stimulation, IC 50 = 710 nM) in mouse [1].…”

“…The activity of Lck was assayed using [g-32 P] ATP (~6000 Ci/mmol: Amersham Pharmacia Biotec, Tokyo, Japan) and peptide substrate (Tyr-AlaGlu) 7 [23] in the presence of various concentrations of the test compounds. The peptide substrate (Tyr-Ala-Glu) 7 was synthesized in our institute.…”