Chemistry can be defined as the study of matter and the changes it undergoes. You¡¯ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology. 671-35-2, Name is 5-Fluoro-4-hydroxypyrimidine, molecular formula is , belongs to pyrimidines compound. In a document, author is Jin, Rui, Recommanded Product: 671-35-2.
Leflunomide Suppresses the Growth of LKB1-Inactivated Tumors in the Immune-Competent Host and Attenuates Distant Cancer Metastasis
Liver kinase B1 (LKB1)-inactivated tumors are vulnerable to the disruption of pyrimidine metabolism, and leflunomide emerges as a therapeutic candidate because its active metabolite, A77-1726, inhibits dihydroorotate dehydrogenase, which is essential for de novo pyrimidine biosynthesis. However, it is unclear whether leflunomide inhibits LKBI-inactivated tumors in vivo, and whether its inhibitory effect on the immune system will promote tumor growth. Here, we carried out a comprehensive analysis of leflunomide treatment in various LKBI-inactivated murine xenografts, patient-derived xenografts, and genetically engineered mouse models. We also generated a mouse tumor-derived cancer cell line, WRJ388, that could metastasize to the lung within a month after subcutaneous implantation in all animals. This model was used to assess the ability of leflunomide to control distant metastasis. Leflunomide treatment shrank a HeLa xenograft and attenuated the growth of an H460 xenograft, a patient-derived xenograft, and lung adenocarcinoma in the immune-competent genetically engineered mouse models. Interestingly, leflunomide suppressed tumor growth through at least three different mechanisms. It caused apoptosis in HeLa cells, induced G(1) cell-cycle arrest in H460 cells, and promoted S-phase cell-cycle arrest in WRJ388 cells. Finally, leflunomide treatment prevented lung metastasis in 78% of the animals in our novel lung cancer metastasis model. In combination, these results demonstrated that leflunomide utilizes different pathways to suppress the growth of LKB1-inactivated tumors, and it also prevents cancer metastasis at distant sites. Therefore, leflunomide should be evaluated as a therapeutic agent for tumors with LKBI inactivation.
Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 671-35-2, in my other articles. Recommanded Product: 671-35-2.
Reference:
Pyrimidine | C4H4N2 – PubChem,
,Pyrimidine – Wikipedia