RESUMO
High-performance liquid chromatography (HPLC) is one of the most useful techniques for the separation and determination of new drugs with a complex nature. The selection of an HPLC detector depends on the chemical nature of molecules, potential impurities, matrix of the sample, sensitivity, availability, and/or cost of the detector. HPLC methods with UV/Vis detectors are the most used and simple analytical procedures in pharmaceutical applications, but it is limited to compounds that possess a chromophore. Hence, this review provides an overview on the development of analytical methods for compounds with weak chromophores. The review described selected papers about HPLC based methods in the PubMed, Scopus, Semantic Scholar and ScienceDirect databases, basically between 2006 and 2023. Of the analytical studies, the HPLC methods with UV-Vis, FLD, CAD, ELSD, RID, ECD, CLND and MS detection were found. This study is a comparison of different types of detection that are described in scientific literature and are routinely used for compounds with weak chromophores. It is expected that this review will be helpful for scientists in the analytical development fields to improve research related to the drug candidates and to ensure its quality according to regulatory levels.
RESUMO
Pharmacologic inhibition of the controlling immunity pathway enzymes arginases 1 and 2 (ARG1 and ARG2) is a promising strategy for cancer immunotherapy. Here, we report the discovery and development of OATD-02, an orally bioavailable, potent arginases inhibitor. The unique pharmacologic properties of OATD-02 are evidenced by targeting intracellular ARG1 and ARG2, as well as long drug-target residence time, moderate to high volume of distribution, and low clearance, which may jointly provide a weapon against arginase-related tumor immunosuppression and ARG2-dependent tumor cell growth. OATD-02 monotherapy had an antitumor effect in multiple tumor models and enhanced an efficacy of the other immunomodulators. Completed nonclinical studies and human pharmacokinetic predictions indicate a feasible therapeutic window and allow for proposing a dose range for the first-in-human clinical study in patients with cancer. SIGNIFICANCE: We have developed an orally available, small-molecule intracellular arginase 1 and 2 inhibitor as a potential enhancer in cancer immunotherapy. Because of its favorable pharmacologic properties shown in nonclinical studies, OATD-02 abolishes tumor immunosuppression induced by both arginases, making it a promising drug candidate entering clinical trials.
