Teriflunomide, the active metabolite of an approved antirheumatic drug leflunomide, is an emerging oral therapy for multiple sclerosis (MS). It reversibly inhibits dihydroorotate dehydrogenase, the rate-limiting step in the de novo synthesis of pyrimidines.
Teriflunomide (Random Configuration) is a disease-modifying immunomodulatory drug with anti-inflammatory properties that selectively and reversibly inhibits the mitochondrial enzyme dihydro-orotate dehydrogenase, with consequent inhibition of de novo pyrimidine synthesis and reduced lymphocyte proliferation. Oral teriflunomide is an effective and generally well tolerated treatment in patients with relapsing multiple sclerosis (MS)[3]. Effects on time to failure were comparable between teriflunomide and IFNβ-1a. There was no difference between teriflunomide (14 mg) and IFNβ-1a on ARR (annualised relapse rate), though ARR was higher with teriflunomide (7 mg)[4]. Low teriflunomide concentrations resulted in cell cycle exit while higher doses led to decreased cell survival. Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation. In vitro myelination can be boosted by means of an early stimulation window with teriflunomide[5].
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