**4. Conclusions**

Compound **1** possesses rich bioactivities, such as excellent fibrinolytic, anti-inflammatory, and anti-oxidative activities. Compared with other anti-thrombotic agents, such as warfarin, compound **1** exhibits less hemorrhage risk for the treatment of thrombosis because it changes the conformation of plasminogen, in the presence of uPA, to activate the plasminogen. Moreover, the inhibition to sEH reduces inflammatory response, causing neuroprotection and less damage from the reperfusion of occluded vessels. The structure–activity relationships of compound **1** indicate that the *N*-linked side chain determines plasminogen activation activity, and the geranylmethyl side chain is essential for anti-inflammatory activity. Recent studies show that compound **1** possesses, surprisingly, anti-cancer activity toward EGFR-TKI-resistant NSCLC cells. Furthermore, the satisfactory pharmacokinetic property and optimized culture methods show that compound **1** has potential as a promising agent. Some modifications of compound **1** and staplabin congeners perform better in fibrinolytic or neuroprotective activity, thereby illustrating the high therapeutic potential.

**Author Contributions:** Conceptualization, investigation, data curation, writing—original draft preparation, and writing—review and editing, S.H.; methodology, formal analysis, project administration, R.S., Y.F. and S.W.; conceptualization, methodology, resources, supervision, project administration, W.W.; conceptualization, methodology, writing—review and editing, supervision, project administration, R.G. Funding acquisition, H.C. and Q.T. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the National Natural Science Foundation of China, gran<sup>t</sup> number 81502955 and 82173731, Shanghai Frontiers Research Center of the Hadal Biosphere and the Science and Technology Research Project of Jiangxi Provincial Department of Education, gran<sup>t</sup> number GJJ201115. Ruilong Sheng appreciated FCT-Fundação para a Ciência e a Tecnologia (Base Fund UIDB/00674/2020 and FCT employment fund 2021.00453.CEECIND) and ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação through the project M1420-01-0145- FEDER-000005-CQM+(Madeira 14-20 Program) and ARDITI-CQM-2017-ISG-003 for sponsorship.

**Institutional Review Board Statement:** Studies not involving humans or animals.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We gratefully acknowledged the financial support from the National Natural Science Foundation of China, Shanghai Frontiers Research Center of the Hadal Biosphere; the Science and Technology Research Project of Jiangxi Provincial Department of Education; FCT-Fundação para a Ciência e a Tecnologia, ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação.

**Conflicts of Interest:** The authors declare no conflict of interest.
