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1,2,4-triazole-based derivatives as dual cyclooxygenases-2 (COX-2)/tumor necrosis factor-alpha (TNF-) inhibitors The cardiac adverse reactions associated with COX-2 selective medications were most severe for coxibs, leading to their removal from the market shortly after their introduction

Hum Reprod (2016) 31(12):284155

It is intended for use in clinical settings where oral administration is not feasible or where higher plasma concentrations are desired, such as in cases of severe deficiency, certain infections, or as adjunctive therapy in specific medical protocols

In addition, the two inhibitors caused HIF-1 protein to drop further below basal levels, indicating that mTOR pathway controls HIF-1 additionally in unstimulated conditions