Introduction
The Inhibition of DHODH
During last decades, researchers had discovered a large number of DHODH inhibitors, such as leflunomide, brequinar, teriflunomide (A77 1726), benzimidazole and so on. Leflunomide is an approved DHODH inhibitor that has been widely used for the treatment of arthritis. As classic DHODH inhibitors, leflunomide and its active metabolite A77 1726 have been demonstrated to suppress cell proliferation or to induce cell death in various tumors. Importantly, DHODH inhibition by leflunomide induced a significant decrease in melanoma growth both in vitro and in vivo studies. Similarly, brequinar sodium is another DHODH inhibitor that showed anti-tumour effect in MC38 colon carcinoma cells when used in combination with fluorouracil. Several other studies also showed that teriflunomide could suppress growth of melanoma cells. Many of the clinically relevant anti-tumor and immunosuppressive drugs target human dihydroorotate dehydrogenase (hDHODH), and the two most promising drugs of such kinds are brequinar (antitumor and immunosuppressive) and leflunomide (immunosuppressive). Recently, the enantiomer (R)-HZ00 was also found to be a cell active and selective inhibitor of DHODH.
DHODH and Diseases
Recently, DHODH was reported to play an essential role during tumorigenesis and cancer development. It is clear that DHODH has been implicated in malaria, autoimmune diseases, cancer, rheumatoid arthritis and psoriasis and other diseases.
During last decades, researchers had discovered a large number of DHODH inhibitors, such as leflunomide, brequinar, teriflunomide (A77 1726), benzimidazole and so on. Leflunomide is an approved DHODH inhibitor that has been widely used for the treatment of arthritis. As classic DHODH inhibitors, leflunomide and its active metabolite A77 1726 have been demonstrated to suppress cell proliferation or to induce cell death in various tumors. Importantly, DHODH inhibition by leflunomide induced a significant decrease in melanoma growth both in vitro and in vivo studies. Similarly, brequinar sodium is another DHODH inhibitor that showed anti-tumour effect in MC38 colon carcinoma cells when used in combination with fluorouracil. Several other studies also showed that teriflunomide could suppress growth of melanoma cells. Many of the clinically relevant anti-tumor and immunosuppressive drugs target human dihydroorotate dehydrogenase (hDHODH), and the two most promising drugs of such kinds are brequinar (antitumor and immunosuppressive) and leflunomide (immunosuppressive). Recently, the enantiomer (R)-HZ00 was also found to be a cell active and selective inhibitor of DHODH.
DHODH and Diseases
Recently, DHODH was reported to play an essential role during tumorigenesis and cancer development. It is clear that DHODH has been implicated in malaria, autoimmune diseases, cancer, rheumatoid arthritis and psoriasis and other diseases.
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