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| {{Short description|Multi-level marketing company}} | |||
| {{Chembox | |||
| {{Use mdy dates|date=March 2020}} | |||
| | ImageFile = TetramethylhexadecenylSuccinylCysteine.png | |||
| | ImageSize = 250px | |||
| | IUPACName = 4-(((1R)-1-carboxy-2-(((2E,7R,11R)-3,7,11,15-tetramethyl-2-hexadecen-1-yl)thio)ethyl)amino)-4-oxo-Butanoic acid | |||
| | OtherNames = SIG1273, TSC | |||
| | Section1 = {{Chembox Identifiers | |||
| | CASNo = 1227280-82-1 | |||
| | PubChem = | |||
| | ChemSpiderID = | |||
| | SMILES = C(CCC(CCC(CCC/C(=C/CSC(NC(=O)CCC(=O)O)C(=O)O)/C)C)C)(C)C | |||
| | InChI = 1S/C27H49NO5S/c1-20(2)9-6-10-21(3)11-7-12-22(4)13-8-14-23(5)17-18-34-19-24(27(32)33)28-25(29)15-16-26(30)31/h17,20-22,24H,6-16,18-19H2,1-5H3,(H,28,29)(H,30,31)(H,32,33)i | |||
| | InChIKey = | |||
| | StdInChI = | |||
| | StdInChIKey = | |||
| }} | |||
| | Section2 = {{Chembox Properties | |||
| | C=27|H=49|N=1|O=5|S=1 | |||
| | LogP = 6.79 | |||
| | SpecificSurfaceArea =129.00 | |||
| }} | |||
| | Section3 = {{Chembox Hazards | |||
| | MainHazards = | |||
| | FlashPt = | |||
| | Autoignition = | |||
| }} | |||
| }} | |||
| '''Signum Biosciences, Inc.''' is a ] company located in Boulder, Colorado. | |||
| '''SIG1273 or Tetramethylhexadecenyl Succinyl Cysteine''' ('''TSC''') is an isoprenylcysteine (IPC) cosmetic functional ingredient (CFI). Similar to first generation CFI, N-acetyl-farnesyl-cysteine <ref name="Gordon1">{{cite journal |title= Topical N-acetyl-S-farnesyl-L-cysteine inhibits mouse skin inflammation, and unlike dexamethasone, its effects are restricted to the application site |journal= Journal of Investigative Dermatology |volume=128 |issue=3 |pages=643–654 | date=March 2008 |pmid=17882268 |doi=10.1038/sj.jid.5701061 |author1=Gordon |first1=J. S. |last2=et |first2= al. }}</ref> (Arazine™), whose ] activities were discovered at ] by Professor Jeffry B. Stock,<ref name="Volker1">{{cite journal |title=Effects of farnesylcysteine analogs on protein carboxyl methylation and signal transduction |journal=Journal of Biological Chemistry |volume=266 |issue=32 |pages=21515–22 | date=November 1991 |pmid=1939182 |author1=Volker |first1=C. |last2=et |first2=al. }}</ref><ref name="Huzoor-Akbar1">{{cite journal |title=Protein prenylcysteine analog inhibits agonist-receptor-mediated signal transduction in human platelets |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=90 |issue=3 |pages=868–72 | date=February 1993 |pmid=8430099 |pmc=45771 |author1=Huzoor-Akbar |first1= |last2=et |first2=al. }}</ref> SIG1273 also has strong anti-inflammatory properties. In addition, SIG1273 is the first IPC molecule to demonstrate ], ] and ] activity.<ref name="Fernandez1">{{cite journal |title=SIG1273: a new cosmetic functional ingredient to reduce blemishes and Propionibacterium acnes in acne prone skin |journal=Journal of Cosmetic Dermatology |volume=11 |issue=4 |pages=272–8 | date=December 2012 |pmid=23174050 |doi=10.1111/jocd.12002 |author1=Fernández |first1=J.R. |last2=et |first2=al. }}</ref><ref name="Fernandez2">{{cite journal |title=Anti-inflammatory and anti-bacterial properties of tetramethylhexadecenyl succinyl cysteine (TSC): a skin-protecting cosmetic functional ingredient |journal=International Journal of Cosmetic Science |volume=37 |issue=1 |pages=129–33 | date=February 2015 |pmid=25256809 |doi=10.1111/ics.12166 |author1=Fernández |first1=J.R. |last2=et |first2=al. }}</ref><ref name="Fernandez3">{{cite journal |title=Anti-inflammatory, anti-aging and anti-bacterial properties of SIG1273: A skin protecting cosmetic functional ingredient |journal=39th Annual Meeting of The Japanese Society for Investigative Dermatology |pages=126 | date=December 2014 |author1=Fernández |first1=J.R. |last2=et |first2=al. }}</ref> | |||
| In mobilizing a protective response from environmental stressors, several different cell types located in the ] release and respond to pro-inflammatory ] ensuring skin homeostasis and health. However, chronic activation of this response, eventually causes damage resulting in premature aging.<ref name="Borg1">{{cite journal |title=The role of cytokines in skin aging |journal=Climacteric |volume=16 |issue=5 |pages=514–21 | date= October 2013 |pmid=23659624 |doi=10.3109/13697137.2013.802303 |author1=Borg |first1=M. |last2=et |first2=al. }}</ref><ref name="Muthusamy1">{{cite journal |title=The UV response of the skin: a review of the MAPK, NFkappaB and TNFalpha signal transduction pathways |journal=Archives of Dermatological Research |volume=302 |issue=1 |pages=5–17 | date= January 2010 |pmid=19756672 |doi=10.1007/s00403-009-0994-y |author1=Muthusamy |first1=V. |last2=Piva |first2=T.J. }}</ref><ref name="Diveu1">{{cite journal |title=Cytokines that regulate autoimmunity |journal=Curr Opin Immunol |volume=20 |issue=6 |pages=663–8 | date= December 2008 |pmid=18834938 |doi=10.1016/j.coi.2008.09.003 |author1=Diveu |first1=C |last2=et |first2=al. }}</ref><ref name="Stamatas1">{{cite journal |title=Early inflammatory processes in the skin |journal=Curr Mol Med |volume=13 |issue=8 |pages=1250–69 | date= September 2013 |pmid=23448341 |author1=Stamatas |first1=G.N. |last2=et |first2=al. }}</ref> SIG1273 combats ] by down modulating these inflammatory pathways in various cell types (], ], ], ]) to protect the skin. | |||
| ==History== | |||
| ==Anti-inflammatory action== | |||
| Signum was founded in 2003 by Maxwell Stock and his father Jeffrey B. Stock in Monmouth Junction, NJ.<ref name=GregoryStockNet>{{cite web |website=gregorystock.net |author=Gregory Stock |url=http://www.gregorystock.net/where-are-the-new-therapeutics.asp |title=Where are the New Therapeutics? |accessdate=10 April 2015 |archiveurl=https://web.archive.org/web/20160304030809/http://www.gregorystock.net/where-are-the-new-therapeutics.asp |archivedate=4 March 2016 |url-status=dead}}</ref> In 2020 the company relocated to Boulder, Colorado.<ref>{{Cite web |date=2020-05-22 |title=Signum Biosciences developing cutting-edge health biotech in Boulder • BLDRfly |url=https://bldrfly.com/features/2020/05/22/health-technology-merge-in-boulder/ |access-date=2023-11-07 |website=BLDRfly |language=en-US}}</ref> | |||
| SIG1273 has demonstrated anti-inflammatory properties in several in vitro cell based models. Using normal human epidermal keratinocytes (NHEKs), SIG1273 was shown to reduce both ] (P. acnes) and peptidoglycan (PGN) induced ] (IL-8) production (IC50 = 3 µM and 0.3 µM respectively).<ref name="Fernandez1" /> Both these ligands stimulate the production of pro-inflammatory cytokines via toll-like receptor-2 (]) and toll-like receptor-4 (]) signaling.<ref name="Jugeau1">{{cite journal |title=Induction of toll-like receptors by Propionibacterium acnes |journal=British Journal of Dermatology |volume=153 |issue=6 |pages=1105–13 | date=December 2005 |pmid=16307644 |doi=10.1111/j.1365-2133.2005.06933.x |author1=Jugeau |first1=S. |last2=et |first2=al. }}</ref><ref name="Kim1">{{cite journal |title=Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses |journal=Dermatology |volume=211 |issue=3 |pages=193–8 | date=November 2005 |pmid=16205063 |doi=10.1159/000087011 |author1=Kim |first1=S. }}</ref><ref name="Nagy1">{{cite journal |title=Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes |journal=Dermatology |volume=211 |issue=3 |pages=193–8 | date=November 2005 |pmid=16797202| doi=10.1016/j.micinf.2006.04.001 |author1=Nagy |first1=I. |author2=et |first2=al. }}</ref> Additional studies performed using NHEKs demonstrates SIG1273 blocks chemical irritant ] (TPA) induced IL-8 and ] (TNF- α) production (IC50 = 10 nM and 11 nM respectively) as well as ] (UVB) induced ] (IL-6) release (IC50 = 3 µM) in a dose dependent manner.<ref name="Fernandez2" /> Both these inflammatory inducers have been previously shown to increase production of several pro-inflammatory mediators in keratinocytes.<ref name="Cataisson1">{{cite journal |title=CXCR2 ligands and G-CSF mediate PKCalpha-induced intraepidermal inflammation |journal=J Clin Invest |volume=116 |issue=10 |pages=2757–2766 | date=October 2006 |pmc=1560349 |pmid=16964312 |doi=10.1172/JCI27514 |author1=Cataisson |first1=C. |last2=et |first2=al. }}</ref><ref name="Imokawa1">{{cite journal |title=Mechanism of UVB-induced wrinkling of the skin: paracrine cytokine linkage between keratinocytes and fibroblasts leading to the stimulation of elastase |journal=J Investig Dermatol Symp Proc |volume=14 |issue=1 |pages=36–43 | date=August 2009 |pmid=19675551 |doi=10.1038/jidsymp.2009.11 |author1=Imokawa |first1=G. }}</ref> | |||
| Previous studies have demonstrated nickel treatment of endothelial cells activates ] resulting in induction of ] and ].<ref name="Schmidt1">{{cite journal |title=Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel |journal=Nat Immunol |volume=11 |issue=9 |pages=3814–9 | date=September 2009 |pmid=20711192 |doi=10.1038/ni.1919 |author1=Schmidt |first1=M. |author2=et |first2=al. }}</ref> Utilizing human dermal microvascular endothelial cells (HDMECs) treated with nickel leads to overproduction of IL-6 and IL-8 which were reduced in the presence of SIG1273 in a dose dependent manner (IC50 = 1 µM and 0.1 µM respectively).<ref name="Fernandez2" /> In addition to keratinocytes and endothelial cells, ] (PBMCs), are an important component of the immune system.<ref name="Numerof1">{{cite journal |title=Cytokine and anti-cytokine therapies for psoriasis and atopic dermatitis |journal=BioDrugs |volume=20 |issue=2 |pages=93–103 | date=2006 |pmid=16626167 |author1=Numerof |first1=R.P. |author2=Asadullah |first2=K. }}</ref> In particular, ] and ] have recently received attention as potential targets for dermal protection.<ref name="Numerof1" /> In cell based studies using PBMCs, SIG1273 was shown to inhibit ] activated IL-4 and IL-17 release in a dose dependent manner (IC50 = 0.7 µM and 0.4 µM respectively).<ref name="Fernandez2" /> | |||
| Signum agreed in 2019 to stop making certain claims about its ''EHT'' supplement, and to stop allowing its ] partner firm Neora (formerly Nerium International) to make such claims. | |||
| ==Anti-aging action== | |||
| ] (MMPs) are thought to be responsible for dermal ] in human skin.<ref name="Herrmann1">{{cite journal |title=UVA irradiation stimulates the synthesis of various matrix-metalloproteinases (MMPs) in cultured human fibroblasts |journal=Experimental Dermatology |volume=2 |issue=2 |pages=193–8 | date=March 1993 |pmid=8156175 |author1=Herrmann |first1=G. |author2=et |first2=al. }}</ref> Specifically, ] or ] is induced by ] (UVA) irradiation<ref name="Fisher1">{{cite journal |title=Pathophysiology of premature skin aging induced by ultraviolet light |journal=N Engl J Med |volume=337 |issue=20 |pages=1419–28 | date=November 1997 |doi=10.1056/NEJM199711133372003 |pmid=9358139 |author1=Fisher |first1=G.J. |author2=et |first2=al. }}</ref> and breaks down the ] (type I, II and III ]) contributing to wrinkle formation. Studies using human dermal fibroblasts (HDFs) demonstrate UVA-induced pro-MMP-1 secretion is reduced dose dependently by SIG1273 (IC50 = 0.3 µM)<ref name="Fernandez3" /> suggesting potential anti-wrinkle activity. | |||
| ===Neora (Nerium) partnership and FTC injunction=== | |||
| ==Anti-acne action== | |||
| In 2015 Signum partnered with Neora, LLC (then known as Nerium International) to launch a ] called eicosanoyl-5-hydroxytryptamide (EHT).<ref name=NeriumEHTPR>{{cite web |date=10 April 2015 |url=https://www.prweb.com/releases/nerium_international_introduces_new_advanced_anti_aging_product_focused_on_optimal_brain_health/prweb12644620.htm |title=Nerium Press Release: Nerium International Introduces New, Advanced Anti-Aging Product Focused on Optimal Brain Health |access-date=27 March 2020 |archive-date=11 May 2019 |archive-url=https://web.archive.org/web/20190511100639/http://www.prweb.com/releases/2015/04/prweb12644620.htm |url-status=live}}</ref> EHT is derived from coffee and inhibits demethylation of the enzyme ] (PPP2CA; PP2A).<ref name=NatureHaas>{{cite journal |last1=Haas |first1=M. J. |title=Extracting PD therapy from coffee |journal=SciBX |date=26 May 2011 |volume=2011 |issue=590 |pages=590 |doi=10.1038/scibx.2011.590 |doi-access=free}}</ref> In October 2019 the ] won a permanent injunction against Signum BioSciences, Signum Nutralogix, and affiliated companies including Neora. The injunction prohibits claims or representations of EHT's efficacy in treating or mitigating ], ], or brain injury including ] and ], unless those claims are backed up by randomized, double-blind, placebo-controlled human clinical testing.<ref name=DMN_Neora_FTC>{{cite web |last1=DiFurio |first1=Dom |title=FTC sues Addison-based Neora for allegedly operating pyramid scheme, pushing concussion treatment |url=https://www.dallasnews.com/business/2019/11/01/ftc-sues-addison-based-neora-for-allegedly-operating-pyramid-scheme-pushing-treatment-for-cte/ |website=dallasnews.com |accessdate=27 March 2020 |archiveurl=https://web.archive.org/web/20200327151326/https://www.dallasnews.com/business/2019/11/01/ftc-sues-addison-based-neora-for-allegedly-operating-pyramid-scheme-pushing-treatment-for-cte/ |archivedate=27 March 2020 |date=1 Nov 2019 |url-status=live}}</ref><ref name=BFN_Neora_FTC>{{cite web |last1=Notopoulos |first1=Katie |title=The FTC Said This Skincare Line Is A Pyramid Scheme |url=https://www.buzzfeednews.com/article/katienotopoulos/ftc-neora-skincare-pyramid-scheme-mlm |website=buzzfeednews.com |accessdate=27 March 2020 |archiveurl=https://web.archive.org/web/20200327152215/https://www.buzzfeednews.com/article/katienotopoulos/ftc-neora-skincare-pyramid-scheme-mlm |archivedate=27 March 2020 |date=6 November 2019 |url-status=live}}</ref> | |||
| SIG1273 was assessed clinically in subjects with ] prone skin.<ref name="Fernandez1" /> In a 30 subject randomized, double-blind controlled study 3% SIG1273 gel or vehicle was applied for 6 weeks. Improvements in the signs and symptoms of acne were observed in subjects applying SIG1273 gel, including reduction of ] lesions, microcomedone counts and Sebutape® scores (suggesting SIG1273 may decrease ] levels).<ref name="Fernandez1" /> In addition, given its in vitro antibacterial activity against ''P. acnes'', facial scrubs were taken to measure ] (CFUs) and showed those applying SIG1273 gel had a ~90% colony reduction over the length of the study, which was statistically significant when compared with the vehicle group.<ref name="Fernandez1" /> | |||
| == External links == | |||
| ==Anti-microbial action== | |||
| SIG1273 has been shown to possess anti-microbial properties ''in vitro'' and ''in vivo''.<ref name="Fernandez1" /> SIG1273 was determined to have a ] (MIC) of 2 µg/ml against ''P. acnes''. ] (MBC) was determined by spotting on ] plates to count colony-forming units (CFUs) and results show SIG1273 at 5 µg/ml and higher to kill ''P. acnes''.<ref name="Fernandez1" /> Another common pathogen for inflammatory skin conditions is ] (''S. pyogenes'').<ref name="ElFerezli1">{{cite journal |title=Streptococcus sp. and Staphylococcus aureus isolates from patients with psoriasis possess genes that code for toxins (superantigens): clinical and therapeutic implications |journal=Immunopharmacol Immunotoxicol |volume=30 |issue=2 |pages=195–205 | date=2008 |pmid=18569077| doi=10.1080/08923970801946808 |author1=El Ferezli |first1=J. |author2=et |first2=al. }}</ref> SIG1273 was shown to prevent ''S. pyogenes'' growth with a MIC of 2 µg/ml.<ref name="Fernandez2" /> | |||
| * | |||
| ==Adverse effects== | |||
| Safety and tolerability studies in human subjects have demonstrated that SIG1273 is safe when applied topically. SIG1273 at 3% was evaluated in a 100 subject human repeated insult patch test and was found to cause no skin sensitization or irritation (Product Investigations).<ref name="Fernandez1" /> In a separate clinical study, 16 subjects applied 3% SIG1273 gel twice daily for 6 weeks and showed no signs of irritation, redness, dryness, burning/stinging and peeling.<ref name="Fernandez1" /> | |||
| ==References== | ==References== | ||
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Latest revision as of 06:20, 15 August 2024
Multi-level marketing company
Signum Biosciences, Inc. is a dietary supplement company located in Boulder, Colorado.
History
Signum was founded in 2003 by Maxwell Stock and his father Jeffrey B. Stock in Monmouth Junction, NJ. In 2020 the company relocated to Boulder, Colorado.
Signum agreed in 2019 to stop making certain claims about its EHT supplement, and to stop allowing its multi-level marketing partner firm Neora (formerly Nerium International) to make such claims.
Neora (Nerium) partnership and FTC injunction
In 2015 Signum partnered with Neora, LLC (then known as Nerium International) to launch a dietary supplement called eicosanoyl-5-hydroxytryptamide (EHT). EHT is derived from coffee and inhibits demethylation of the enzyme protein phosphatase 2 (PPP2CA; PP2A). In October 2019 the Federal Trade Commission won a permanent injunction against Signum BioSciences, Signum Nutralogix, and affiliated companies including Neora. The injunction prohibits claims or representations of EHT's efficacy in treating or mitigating Alzheimer's disease, Parkinson's disease, or brain injury including CTE and concussion, unless those claims are backed up by randomized, double-blind, placebo-controlled human clinical testing.
External links
References
- Gregory Stock. "Where are the New Therapeutics?". gregorystock.net. Archived from the original on March 4, 2016. Retrieved April 10, 2015.
- "Signum Biosciences developing cutting-edge health biotech in Boulder • BLDRfly". BLDRfly. May 22, 2020. Retrieved November 7, 2023.
- "Nerium Press Release: Nerium International Introduces New, Advanced Anti-Aging Product Focused on Optimal Brain Health". April 10, 2015. Archived from the original on May 11, 2019. Retrieved March 27, 2020.
- Haas, M. J. (May 26, 2011). "Extracting PD therapy from coffee". SciBX. 2011 (590): 590. doi:10.1038/scibx.2011.590.
- DiFurio, Dom (November 1, 2019). "FTC sues Addison-based Neora for allegedly operating pyramid scheme, pushing concussion treatment". dallasnews.com. Archived from the original on March 27, 2020. Retrieved March 27, 2020.
- Notopoulos, Katie (November 6, 2019). "The FTC Said This Skincare Line Is A Pyramid Scheme". buzzfeednews.com. Archived from the original on March 27, 2020. Retrieved March 27, 2020.