Much more than you expected: The non-DHFR-mediated effects of methotrexate
Abstract Background For decades, methotrexate (MTX; amethopterin) has been known as an antifolate inhibitor of dihydrofolate reductase (DHFR), and it is widely used for the treatment of various malignancies and autoimmune diseases. Although the inclusion of MTX in various therapeutic regimens is based on its ability to inhibit DHFR and consequently to suppress the synthesis of pyrimidine and purine precursors, recent studies have shown that MTX is also able to target other intracellular pathways that are independent of folate metabolism. Scope of review The main aim of this review is to summarize the most important, up-to-date findings of studies regarding the non-DHFR-mediated mechanisms of MTX action. Major conclusions The effectiveness of MTX is undoubtedly caused by its capability to affect various intracellular pathways at many levels. Although the most important therapeutic mechanism of MTX is strongly based on the inhibition of DHFR, many other effects of this compound have been described and new studies bring new insights into the pharmacology of MTX every year. General significance Identification of these new targets for MTX is especially important for a better understanding of MTX action in new protocols of combination therapy. Highlights Methotrexate is widely used as an inhibitor of dihydrofolate reductase for decades. Methotrexate affects also pathways that are independent of folate metabolism. The diverse effects of methotrexate are apparently concentration-dependent. Identification of these new targets is important for combination therapy.
유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.
원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.
- 이 논문과 함께 출판된 논문 + 더보기