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Tetramethyl\u2010hexadecenyl\u2010cysteine\u2010formylprolinate (SIG1459), a novel anti\u2010acne isoprenylcysteine (IPC) small molecule, is shown in this study to have direct antibacterial activity and inhibit TLR2 inflammatory signalling. In vitro antibacterial activity of SIG1459 against <jats:italic>C.\u00a0acnes<\/jats:italic> was established demonstrating minimal inhibitory concentration (MIC\u00a0=\u00a08.5\u00a0\u03bcmol\\L), minimal bactericidal concentration (MBC\u00a0=\u00a016.1\u00a0\u03bcmol\\L) and minimal biofilm eradication concentration (MBEC\u00a0=\u00a012.5\u00a0\u03bcmol\\L). To assess SIG1459's anti\u2010inflammatory activity, human keratinocytes were exposed to <jats:italic>C.\u00a0acnes<\/jats:italic> and different TLR2 ligands (peptidoglycan, FSL\u20101, Pam3CSK4) that induce pro\u2010inflammatory cytokine IL\u20108 and IL\u20101\u03b1 production. Results demonstrate SIG1459 inhibits TLR2\u2010induced IL\u20108 release from TLR2\/TLR2 (IC<jats:sub>50<\/jats:sub>\u00a0=\u00a00.086\u00a0\u03bcmol\\L), TLR2\/6 (IC<jats:sub>50<\/jats:sub>\u00a0=\u00a00.209\u00a0\u03bcmol\\L) and IL\u20101\u03b1 from TLR2\/TLR2 (IC<jats:sub>50<\/jats:sub>\u00a0=\u00a00.050\u00a0\u03bcmol\\L). To assess the safety and in vivo anti\u2010acne activity of SIG1459, a vehicle controlled clinical study was conducted applying 1% SIG1459 topically (n\u00a0=\u00a035 subjects) in a head\u2010to\u2010head comparison against 3% BPO (n\u00a0=\u00a015 subjects). Utilizing the Investigator Global Assessment scale for acne as primary endpoint, results demonstrate 1% SIG1459 significantly outperformed 3% BPO over 8\u00a0weeks, resulting in 79% improvement as compared to 56% for BPO. Additionally, 1% SIG1459 was well tolerated. Thus, SIG1459 and phytyl IPC compounds represent a novel anti\u2010acne technology that provides a safe dual modulating benefit by killing <jats:italic>C.\u00a0acnes<\/jats:italic> and reducing the inflammation it triggers via TLR2 signalling.<\/jats:p>","DOI":"10.1111\/exd.13692","type":"journal-article","created":{"date-parts":[[2018,5,24]],"date-time":"2018-05-24T08:35:12Z","timestamp":1527150912000},"page":"993-999","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["SIG1459: A novel phytyl\u2010cysteine derived TLR2 modulator with in vitro and clinical anti\u2010acne activity"],"prefix":"10.1111","volume":"27","author":[{"given":"Jos\u00e9 R.","family":"Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"Webb","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Rouzard","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Healy","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Tamura","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Voronkov","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen L.","family":"Huber","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffry B.","family":"Stock","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"},{"name":"Department of Molecular Biology Princeton University  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell","family":"Stock","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-6896","authenticated-orcid":false,"given":"Edwardo","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Signum Dermalogix  Monmouth Junction NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(98)70442-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1099\/ijsem.0.001367"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sder.2008.06.002"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1988.tb01775.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2004.03.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087011"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","unstructured":"J.Kim M. 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