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==Antimicrobial agent==
==Antimicrobial agent==
* [[wikt:antifungal|antifungal]] activity via disruption of [[phosphoinositide-dependent kinase-1]] activity.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/23652278 OSU-03012, a non-cox inhibiting celecoxib derivative, induces apoptosis of human esophageal carcinoma cells through a p53/Bax/cytochrome c/caspase-9-dependent pathway]</ref>
* [[wikt:antifungal|antifungal]] activity via disruption of [[phosphoinositide-dependent kinase-1]] activity.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/23652278 OSU-03012, a non-cox inhibiting celecoxib derivative, induces apoptosis of human esophageal carcinoma cells through a p53/Bax/cytochrome c/caspase-9-dependent pathway]</ref>
* OSU-03012 has also illustrated [[antiparasitic]] activity against ''[[Leishmania donovani]]''<ref>{{cite journal|last1=Collier|first1=MA|last2=Peine|first2=KJ|last3=Gautum|first3=S|last4=Oghumu|first4=S|last5=Varikuti|first5=S|last6=Borteh|first6=H|last7=Papenfuss|first7=TL|last8=Satoskar|first8=AR|last9=Bachelder|first9=EM|last10=Ainslie|first10=KM|title=Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles|journal=International Journal of Pharmaceutics|date=Feb 29, 2016|volume=499|issue=1-2|page=186-94|pmid=26768723|url=https://www.ncbi.nlm.nih.gov/pubmed/26768723}}</ref>,
* OSU-03012 has also illustrated [[antiparasitic]] activity against ''[[Leishmania donovani]]''<ref>{{cite journal|last1=Collier|first1=MA|last2=Peine|first2=KJ|last3=Gautum|first3=S|last4=Oghumu|first4=S|last5=Varikuti|first5=S|last6=Borteh|first6=H|last7=Papenfuss|first7=TL|last8=Satoskar|first8=AR|last9=Bachelder|first9=EM|last10=Ainslie|first10=KM|title=Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles|journal=International Journal of Pharmaceutics|date=Feb 29, 2016|volume=499|issue=1-2|page=186-94|pmid=26768723|url=https://www.ncbi.nlm.nih.gov/pubmed/26768723}}</ref><ref>{{cite web|last1=Ainslie|first1=et al.|title=COMPOSITIONS AND METHODS FOR INHIBITING LEISHMANIA|url=http://www.freepatentsonline.com/y2016/0120844.html|website=Free Patents Online}}</ref>
* Antibacterial activity against ''[[Salmonella enterica]]''<ref>{{cite journal|last1=Chiu|first1=HC|last2=Kulp|first2=SK|last3=Soni|first3=S|last4=Wang|first4=D|last5=Gunn|first5=JS|last6=Schlesinger|first6=LS|last7=Chen|first7=CS|title=Eradication of intracellular Salmonella enterica serovar Typhimurium with a small-molecule, host cell-directed agent.|journal=Antimicrob Agents Chemother|date=Dec 2009|volume=53|issue=12|page=5236|pmid=19805568|url=https://www.ncbi.nlm.nih.gov/pubmed/19805568}}</ref><ref>{{cite journal|last1=Hoang|first1=KV|last2=Borteh|first2=HM|last3=Rajaram|first3=MV|last4=Peine|first4=KJ|last5=Curry|first5=H|last6=Collier|first6=MA|last7=Homsy|first7=ML|last8=Bachelder|first8=EM|last9=Gunn|first9=JS|last10=Schlesinger|first10=LS|last11=Ainslie|first11=KM|title=Acetalated dextran encapsulated AR-12 as a host-directed therapy to control Salmonella infection.|journal=Int J Pharm|date=Dec 2014|volume=477|issue=1-2|page=334|pmid=25447826|url=https://www.ncbi.nlm.nih.gov/pubmed/25447826}}</ref>, and ''[[Francisella tularensis]]''<ref>{{cite journal|last1=Chiu|first1=HC|last2=Soni|first2=S|last3=Kulp|first3=SK|last4=Curry|first4=H|last5=Wang|first5=D|last6=Gunn|first6=JS|last7=Schlesinger|first7=LS|last8=Chen|first8=CS|title=Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent.|journal=J Biomed Sci|date=Dec 2009|volume=16|page=110|pmid=20003180|url=https://www.ncbi.nlm.nih.gov/pubmed/20003180}}</ref>
* [[Antibiotics|Antibacterial]] activity against ''[[Salmonella enterica]]''<ref>{{cite journal|last1=Chiu|first1=HC|last2=Kulp|first2=SK|last3=Soni|first3=S|last4=Wang|first4=D|last5=Gunn|first5=JS|last6=Schlesinger|first6=LS|last7=Chen|first7=CS|title=Eradication of intracellular Salmonella enterica serovar Typhimurium with a small-molecule, host cell-directed agent.|journal=Antimicrob Agents Chemother|date=Dec 2009|volume=53|issue=12|page=5236|pmid=19805568|url=https://www.ncbi.nlm.nih.gov/pubmed/19805568}}</ref><ref>{{cite journal|last1=Hoang|first1=KV|last2=Borteh|first2=HM|last3=Rajaram|first3=MV|last4=Peine|first4=KJ|last5=Curry|first5=H|last6=Collier|first6=MA|last7=Homsy|first7=ML|last8=Bachelder|first8=EM|last9=Gunn|first9=JS|last10=Schlesinger|first10=LS|last11=Ainslie|first11=KM|title=Acetalated dextran encapsulated AR-12 as a host-directed therapy to control Salmonella infection.|journal=Int J Pharm|date=Dec 2014|volume=477|issue=1-2|page=334|pmid=25447826|url=https://www.ncbi.nlm.nih.gov/pubmed/25447826}}</ref>, and ''[[Francisella tularensis]]''<ref>{{cite journal|last1=Chiu|first1=HC|last2=Soni|first2=S|last3=Kulp|first3=SK|last4=Curry|first4=H|last5=Wang|first5=D|last6=Gunn|first6=JS|last7=Schlesinger|first7=LS|last8=Chen|first8=CS|title=Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent.|journal=J Biomed Sci|date=Dec 2009|volume=16|page=110|pmid=20003180|url=https://www.ncbi.nlm.nih.gov/pubmed/20003180}}</ref>
* [[antiviral protein|Antiviral]] when combined with [[PDE5 inhibitor]]s such as [[sildenafil]] or [[tadalafil]] against a wide variety of organisms, with this activity thought to be mediated via inhibition of the [[chaperone protein]] [[Binding immunoglobulin protein|BiP]].<ref>Paul Dent et al. GRP78 / BiP / HSPA5 / Dna K is a universal therapeutic target for human disease. ''Journal of Cellular Physiology'' 2014 DOI: 10.1002/jcp.24919</ref>
* [[antiviral protein|Antiviral]] when combined with [[PDE5 inhibitor]]s such as [[sildenafil]] or [[tadalafil]] against a wide variety of organisms, with this activity thought to be mediated via inhibition of the [[chaperone protein]] [[Binding immunoglobulin protein|BiP]].<ref>Paul Dent et al. GRP78 / BiP / HSPA5 / Dna K is a universal therapeutic target for human disease. ''Journal of Cellular Physiology'' 2014 DOI: 10.1002/jcp.24919</ref>


Revision as of 17:13, 13 June 2017

OSU-03012
File:OSU-03012.png
Names
IUPAC name
2-amino-N-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]acetamide
Other names
OSU-03012
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
  • InChI=1S/C26H19F3N4O/c27-26(28,29)24-14-23(33(32-24)20-10-8-19(9-11-20)31-25(34)15-30)18-7-12-22-17(13-18)6-5-16-3-1-2-4-21(16)22/h1-14H,15,30H2,(H,31,34)
    Key: YULUCECVQOCQFQ-UHFFFAOYSA-N
  • InChI=1/C26H19F3N4O/c27-26(28,29)24-14-23(33(32-24)20-10-8-19(9-11-20)31-25(34)15-30)18-7-12-22-17(13-18)6-5-16-3-1-2-4-21(16)22/h1-14H,15,30H2,(H,31,34)
    Key: YULUCECVQOCQFQ-UHFFFAOYAU
  • C1=CC=C2C(=C1)C=CC3=C2C=CC(=C3)C4=CC(=NN4C5=CC=C(C=C5)NC(=O)CN)C(F)(F)F
Properties
C26H19F3N4O
Molar mass 460.460 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

OSU-03012 (AR-12) is a celecoxib derivative with anticancer and anti-microbial activity. Unlike celecoxib, OSU-03012 does not inhibit COX, but inhibits several other important enzymes instead which may be useful in the treatment of some forms of cancer,[1][2] When combined with PDE5 inhibitors such as sildenafil or tadalafil, OSU-03012 was found to show enhanced anti-tumour effects.[3]

Antimicrobial agent

Orphan drug designation

The European Commission has designated AR-12 as an orphan drug for use in combination with other drugs for treatment of two infections diseases, cryptococcosis and tularaemia. AR-12 received an orphan drug designation in combination with the antifungal drug fluconazole for cryptococcosis of the brain. It also received this designation for tularaemia in combination with the antibacterial drug gentamicin.[11]

References

  1. ^ Booth L, Cruickshanks N, Ridder T, Chen CS, Grant S, Dent P. OSU-03012 interacts with lapatinib to kill brain cancer cells. Cancer Biology and Therapy. 2012 Dec;13(14):1501-11. doi: 10.4161/cbt.22275 PMID 22990204
  2. ^ Ma Y, McCarty SK, Kapuriya NP, Brendel VJ, Wang C, Zhang X, Jarjoura D, Saji M, Chen CS, Ringel MD. Development of p21 activated kinase-targeted multikinase inhibitors that inhibit thyroid cancer cell migration. Journal of Clinical Endocrinology and Metabolism. 2013 Aug;98(8):E1314-22. doi: 10.1210/jc.2012-3937 PMID 23709653
  3. ^ Booth L, Roberts JL, Cruickshanks N, Grant S, Poklepovic A, Dent P. Regulation of OSU-03012 toxicity by ER stress proteins and ER stress-inducing drugs. Molecular Cancer Therapeutics. 2014 Oct;13(10):2384-98. doi: 10.1158/1535-7163.MCT-14-0172 PMID 25103559
  4. ^ OSU-03012, a non-cox inhibiting celecoxib derivative, induces apoptosis of human esophageal carcinoma cells through a p53/Bax/cytochrome c/caspase-9-dependent pathway
  5. ^ Collier, MA; Peine, KJ; Gautum, S; Oghumu, S; Varikuti, S; Borteh, H; Papenfuss, TL; Satoskar, AR; Bachelder, EM; Ainslie, KM (Feb 29, 2016). "Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles". International Journal of Pharmaceutics. 499 (1–2): 186-94. PMID 26768723.
  6. ^ Ainslie; et al. "COMPOSITIONS AND METHODS FOR INHIBITING LEISHMANIA". Free Patents Online. {{cite web}}: Explicit use of et al. in: |first1= (help)
  7. ^ Chiu, HC; Kulp, SK; Soni, S; Wang, D; Gunn, JS; Schlesinger, LS; Chen, CS (Dec 2009). "Eradication of intracellular Salmonella enterica serovar Typhimurium with a small-molecule, host cell-directed agent". Antimicrob Agents Chemother. 53 (12): 5236. PMID 19805568.
  8. ^ Hoang, KV; Borteh, HM; Rajaram, MV; Peine, KJ; Curry, H; Collier, MA; Homsy, ML; Bachelder, EM; Gunn, JS; Schlesinger, LS; Ainslie, KM (Dec 2014). "Acetalated dextran encapsulated AR-12 as a host-directed therapy to control Salmonella infection". Int J Pharm. 477 (1–2): 334. PMID 25447826.
  9. ^ Chiu, HC; Soni, S; Kulp, SK; Curry, H; Wang, D; Gunn, JS; Schlesinger, LS; Chen, CS (Dec 2009). "Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent". J Biomed Sci. 16: 110. PMID 20003180.
  10. ^ Paul Dent et al. GRP78 / BiP / HSPA5 / Dna K is a universal therapeutic target for human disease. Journal of Cellular Physiology 2014 DOI: 10.1002/jcp.24919
  11. ^ Arno Therapeutics Inc receives european orphan drug designation for AR-12 to reat two infectious diseases. Reuters, 30 Apr 2015.
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