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Carbonic anhydrase IX (hCAIX) is a membrane-spanning metalloenzyme, encoded by CA9 gene, which can lead to various carcinomas if upregulated. Due to its overexpression in many cancer tissues, hCAIX has become a promising target for developing anticancer therapeutics. Furthermore, several classes of small-molecules have shown to inhibit the hCAIX expression. In this study, therefore, we screened (n = 42) plant-derived compounds to identify the most potent hCAIX inhibitors and to understand their interactions with hCAIX and drug candidacy