**1. Introduction**

Marine natural products harbor unique chemical structures and exhibit diverse biological activity with potential therapeutic utilities that merit investigation [1]. Synthetic drugs with proteasome inhibition, Velcade (bortezomib), Kyprolis (carfilzomib), and Ninlaro (ixazomib), exemplify therapeutic efficacy for the treatment of multiple myeloma [2,3]. In an effort to develop target-direct drug screening assay, we validated a sensitive and efficient high-content screening assay for discovery of proteasome inhibitor. Our initial efforts identified four natural products of soft corals cembrane-based compounds (sarcophytonin A, sarcophytoxide, sarcophine, and laevigatol A) which potentiate proteasome inhibition [4]. We postulate that proteasome inhibitors may benefit the ecosystem of soft coral reef holobiont. Therefore, we continued the drug screening in an effort to identify marine natural products purified from Formosan soft corals in our laboratory. In this study, we demonstrated the identification of six compounds with proteasome inhibitory activity. Structure elucidation revealed they are dolabellane- and secosteroid-based compounds including a new dolabellane, clavinflol C (**1**), three known dolabellanes, stolonidiol (**2**), stolonidiol-17-acetate (**3**), and clavinflol B (**4**) as well as two new secosteroids, 3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9,23-dione (**5**) and 3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9,23-dione (**6**) (Figure 1).

**Figure 1.** Marine natural products exhibit proteasome inhibition by high-content assays. Dolabellanes are clavinflol C (**1**), stolonidiol (**2**), stolonidiol-17-acetate (**3**), and clavinflol B (**4**). Secosteroids are 3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9,23-dione (**5**) and 3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9,23-dione (**6**).
