Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Articles Article Faculty Publications -Articles Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Identification and structure-activity relationship studies of small molecule inhibitors of the human cathepsin D Subject The topic of the resource Cathepsin D Description An account of the resource Cathepsin D, an aspartyl protease, is an attractive therapeutic target for various diseases, primarily cancer and osteoarthritis. However, despite several small molecule cathepsin D inhibitors being developed, that are highly potent, most of them show poor microsomal stability, which in turn limits their clinical translation. Herein, we describe the design, optimization and evaluation of a series of novel non-peptidic acylguanidine based small molecule inhibitors of cathepsin D. Optimization of our hit compound 1a (IC50 = 29 nM) led to the highly potent mono sulphonamide analogue 4b (IC50 = 4 nM), however with poor microsomal stability (HLM: 177 and MLM: 177 ?l/min/mg). To further improve the microsomal stability while retaining the potency, we carried out an extensive structureactivity relationship screen which led to the identification of our optimised lead 24e (IC50 = 45 nM), with an improved microsomal stability (HLM: 59.1 and MLM: 86.8 ?l/min/mg). Our efforts reveal that 24e could be a good starting point or potential candidate for further preclinical studies against diseases where Cathepsin D plays an important role. 2020 Elsevier Ltd Creator An entity primarily responsible for making the resource Goyal S.; Patel K.V.; Nagare Y.; Raykar D.B.; Raikar S.S.; Dolas A.; Khurana P.; Cyriac R.; Sarak S.; Gangar M.; Agarwal A.K.; Kulkarni A. Source A related resource from which the described resource is derived Bioorganic and Medicinal Chemistry, Vol-29 Publisher An entity responsible for making the resource available Elsevier Ltd Date A point or period of time associated with an event in the lifecycle of the resource 2021-01-01 Identifier An unambiguous reference to the resource within a given context <a href="https://doi.org/10.1016/j.bmc.2020.115879" target="_blank" rel="noreferrer noopener">https://doi.org/10.1016/j.bmc.2020.115879</a> <br /><br /><a href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85096839622&amp;doi=10.1016%2Fj.bmc.2020.115879&amp;partnerID=40&amp;md5=cbc04b74b21b3986672c52d072669a3f" target="_blank" rel="noreferrer noopener">https://www.scopus.com/inward/record.uri?eid=2-s2.0-85096839622&amp;doi=10.1016%2fj.bmc.2020.115879&amp;partnerID=40&amp;md5=cbc04b74b21b3986672c52d072669a3f</a> Rights Information about rights held in and over the resource Restricted Access Relation A related resource ISSN: 9680896; PubMed ID: 33271453; CODEN: BMECE Format The file format, physical medium, or dimensions of the resource Online Language A language of the resource English Type The nature or genre of the resource Article Coverage The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant Goyal S., Aten Porus Lifesciences, Bangalore, 560068, India; Patel K.V., Aten Porus Lifesciences, Bangalore, 560068, India; Nagare Y., Aten Porus Lifesciences, Bangalore, 560068, India; Raykar D.B., Aten Porus Lifesciences, Bangalore, 560068, India; Raikar S.S., Aten Porus Lifesciences, Bangalore, 560068, India; Dolas A., Aten Porus Lifesciences, Bangalore, 560068, India; Khurana P., Aten Porus Lifesciences, Bangalore, 560068, India; Cyriac R., Aten Porus Lifesciences, Bangalore, 560068, India; Sarak S., Aten Porus Lifesciences, Bangalore, 560068, India; Gangar M., Aten Porus Lifesciences, Bangalore, 560068, India; Agarwal A.K., Department of Chemistry, CHRIST (Deemed to be University), Bengaluru, Karnataka, India; Kulkarni A., Aten Porus Lifesciences, Bangalore, 560068, India, Avaliv Therapeutics, Naples, FL, United States