# Ex-Rad

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> Source: https://en.wikipedia.org/wiki/Ex-Rad
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{{Short description|Chemical compound}}
{{Chembox
| Verifiedfields = changed
| verifiedrevid = 420924348
| ImageFile = Ex-rad.png
| ImageClass = skin-invert-image
| ImageSize =
| ImageAlt =
| PIN = Sodium 4-<nowiki/>{(1''E'')-2-[(4-chlorophenyl)methanesulfonyl]ethen-1-yl}benzoate
| OtherNames =
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 922139-31-9
| ChEMBL = 2219410
| ChemSpiderID = 17588427
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1068SXU525
| PubChem = 23668369
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D10376
| StdInChI=1S/C16H13ClO4S.Na/c17-15-7-3-13(4-8-15)11-22(20,21)10-9-12-1-5-14(6-2-12)16(18)19;/h1-10H,11H2,(H,18,19);/q;+1/p-1/b10-9+;
| StdInChIKey = PRFBWBYKWZVQJF-RRABGKBLSA-M
| SMILES = C1=CC(=CC=C1CS(=O)(=O)/C=C/C2=CC=C(C=C2)C(=O)[O-])Cl.[Na+] }}
|Section2={{Chembox Properties
| C=16 | H=12 | Cl=1 | Na=1 | O=4 | S=1
| MolarMass =
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| MeltingPt =
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|Section3={{Chembox Hazards
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}}
'''Ex-Rad''' (or '''Ex-RAD'''; '''recilisib sodium''' ([INN](/source/International_Nonproprietary_Name), [USAN](/source/United_States_Approved_Name)); development code '''ON 01210.Na''') is an experimental drug being [developed](/source/drug_development) by Onconova Therapeutics and the [U.S. Department of Defense](/source/United_States_Department_of_Defense).<ref name=pr2010>{{cite press release|url=http://www.eurekalert.org/pub_releases/2010-09/poc-otp092710.php |title=Onconova Therapeutics presents new data demonstrating radioprotection by Ex-RAD at RRS annual meeting |date=2010-09-27 |publisher=EurekAlert |archiveurl=https://archive.today/20130414200645/http://www.eurekalert.org/pub_releases/2010-09/poc-otp092710.php |archivedate=2013-04-14 |accessdate=2011-03-22 |url-status=dead }}</ref> It is being studied as a radiation protection agent.<ref>{{cite web | url = https://adisinsight.springer.com/drugs/800020974 | title = Recilisib | publisher = Adis Insight }}</ref> Chemically, it is the sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone.<ref name=ghosh2009>{{cite journal |doi=10.1667/RR1367.1 |title=Radiation Protection by a New Chemical Entity, Ex-Rad: Efficacy and Mechanisms |year=2009 |last1=Ghosh |first1=Sanchita P. |last2=Perkins |first2=Michael W. |last3=Hieber |first3=Kevin |last4=Kulkarni |first4=Shilpa |last5=Kao |first5=Tzu-Cheg |last6=Reddy |first6=E. Premkumar |last7=Reddy |first7=M. V. Ramana |last8=Maniar |first8=Manoj |last9=Seed |first9=Thomas |last10=Kumar |first10=K. Sree |journal=Radiation Research |volume=171 |issue=2 |pages=173–9 |pmid=19267542|bibcode=2009RadR..171..173G |s2cid=207252424 }}</ref>

==Clinical trials==
The results of two [Phase I](/source/Clinical_trial) clinical studies in healthy human volunteers indicate that subcutaneously injected Ex-Rad is safe and well tolerated, with "no evidence of systemic side effects".<ref name=onsite>{{cite web|url=http://www.onconova.com/exrad.shtml |title=Ex-RAD® for Protection from Radiation Injury |year=2009 |publisher=Onconova Therapeutics |archiveurl=https://web.archive.org/web/20110320025810/http://www.onconova.com/exrad.shtml |archivedate=2011-03-20 |accessdate=2011-03-22 |url-status=dead }}</ref> A study in mice demonstrated the efficacy of Ex-Rad by increasing the survival rate of mice exposed to typically lethal whole-body [irradiation](/source/irradiation). The study tested oral and [parenteral](/source/parenteral) administration of Ex-Rad for both pre- and post-exposure radiomitigation.<ref name=pr2010 />

Research on Ex-Rad has involved collaboration with the [Armed Forces Radiobiology Research Institute](/source/Armed_Forces_Radiobiology_Research_Institute) (AFRRI), the Department of Biochemistry and Molecular & Cellular Biology at [Georgetown University](/source/Georgetown_University), [Long Island University](/source/Long_Island_University)'s Arnold & Marie Schwartz College of Pharmacy, and the Department of Oncological Sciences at the [Mt. Sinai School of Medicine](/source/Mount_Sinai_School_of_Medicine).<ref name=pr2010 />

==Mechanism of action==
Onconova reports that Ex-Rad protects cells exposed to radiation against [DNA](/source/DNA) damage, and that the drug's mechanism of action does not involve scavenging [free radicals](/source/free_radicals) or arresting the [cell cycle](/source/cell_cycle). Instead, they claim it employs a "novel mechanism" involving "intracellular signaling, damage sensing, and DNA repair pathways".<ref name=onsite /> Ex-RAD is a chlorobenzylsulfone derivative that works after free radicals have damaged DNA. Onconova CEO Ramesh Kumar believes this is a better approach than trying to scavenge free radicals. “Free radicals are very short-lived, and so the window of opportunity to give a drug is very narrow,” he says. In cell and animal models, Ex-RAD protects [hematopoietic](/source/hematopoietic) and [gastrointestinal](/source/gastrointestinal) tissues from radiation injury when given either before or after exposure.<ref name="cen"/>

==See also==
*[CBLB502](/source/CBLB502) (Entolimod), a compound being studied for its ability to suppresses [apoptotic](/source/apoptotic) cell death in [hematopoietic](/source/hematopoietic) and [gastrointestinal](/source/gastrointestinal) cells.<ref name="cen">{{cite journal | url = http://cen.acs.org/articles/90/i26/Drugs-Never-Used.html | title = The Drugs That May Never Be Used | volume = 90 | issue = 26 | pages = 23–26 | date = 2012 | journal = [Chemical & Engineering News](/source/Chemical_%26_Engineering_News) }}</ref>
*[Amifostine](/source/Amifostine) (WR2721), the first selective-target and broad-spectrum radioprotector, upregulates [DNA repair](/source/DNA_repair)<ref>{{cite journal |doi=10.1634/theoncologist.12-6-738 |title=Amifostine: The First Selective-Target and Broad-Spectrum Radioprotector |year=2007 |last1=Kouvaris |first1=J. R. |last2=Kouloulias |first2=V. E. |last3=Vlahos |first3=L. J. |journal=The Oncologist |volume=12 |issue=6 |pages=738–47 |pmid=17602063|doi-access=free }}</ref>
*[Filgrastim](/source/Filgrastim) (Neupogen), a hematopoietic countermeasure of [acute radiation syndrome](/source/acute_radiation_syndrome) (ARS)
*[Pegfilgrastim](/source/Pegfilgrastim) (Neulasta), longer acting than its parent, filgrastim
*[Sargramostim](/source/Sargramostim) (leukine), similar in use to filgrastim
*[''N''-Acetylcysteine](/source/N-Acetylcysteine), protects against DNA damage, suggested to be comparable to amifostine<ref>{{cite journal |doi=10.1016/j.mrfmmm.2009.02.016 |pmid=19427509 |title=N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals |year=2009 |last1=Reliene |first1=Ramune |last2=Pollard |first2=Julianne M. |last3=Sobol |first3=Zhanna |last4=Trouiller |first4=Benedicte |last5=Gatti |first5=Richard A. |last6=Schiestl |first6=Robert H. |journal=Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis |volume=665 |issue=1–2 |pages=37–43 |bibcode=2009MRFMM.665...37R }}</ref><ref>{{cite journal |doi=10.1016/j.bcp.2007.09.018 |title=Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats |year=2008 |last1=Mansour |first1=Heba H. |last2=Hafez |first2=Hafez F. |last3=Fahmy |first3=Nadia M. |last4=Hanafi |first4=Nemat |journal=Biochemical Pharmacology |volume=75 |issue=3 |pages=773–80 |pmid=18028880}}</ref><ref>{{cite journal |pmid=19218780 |year=2009 |last1=Demirel |first1=C |last2=Kilçiksiz |first2=S |last3=Ay |first3=OI |last4=Gürgül |first4=S |last5=Ay |first5=ME |last6=Erdal |first6=N |title=Effect of N-acetylcysteine on radiation-induced genotoxicity and cytotoxicity in rat bone marrow |volume=50 |issue=1 |pages=43–50 |journal=Journal of Radiation Research |doi=10.1269/jrr.08066|bibcode=2009JRadR..50...43D |doi-access=free }}</ref><ref>{{cite journal |pmid=20941831 |year=2010 |last1=Demirel |first1=C |last2=Kilciksiz |first2=S |last3=Evirgen-Ayhan |first3=S |last4=Gurgul |first4=S |last5=Erdal |first5=N |title=The preventive effect of N-acetylcysteine on radiation-induced dermatitis in a rat model |volume=15 |issue=3 |pages=577–82 |journal=Journal of the Balkan Union of Oncology}}</ref>
*[Thrombomodulin](/source/Thrombomodulin)<ref name="ncbi">{{cite journal |doi=10.1038/nm.2813 |title=Pharmacological targeting of the thrombomodulin–activated protein C pathway mitigates radiation toxicity |year=2012 |last1=Geiger |first1=Hartmut |last2=Pawar |first2=Snehalata A |last3=Kerschen |first3=Edward J |last4=Nattamai |first4=Kalpana J |last5=Hernandez |first5=Irene |last6=Liang |first6=Hai Po H |last7=Fernández |first7=Jose Á |last8=Cancelas |first8=Jose A |last9=Ryan |first9=Marnie A |last10=Kustikova |first10=Olga |last11=Schambach |first11=Axel |last12=Fu |first12=Qiang |last13=Wang |first13=Junru |last14=Fink |first14=Louis M |last15=Petersen |first15=Karl-Uwe |last16=Zhou |first16=Daohong |last17=Griffin |first17=John H |last18=Baum |first18=Christopher |last19=Weiler |first19=Hartmut |last20=Hauer-Jensen |first20=Martin |journal=Nature Medicine |volume=18 |issue=7 |pages=1123–9 |pmid=22729286 |pmc=3491776}}</ref>
*[Activated protein C](/source/Activated_protein_C)<ref name="ncbi" />
*[Chelation therapy](/source/Chelation_therapy), a countermeasure for treating internal [radio-isotope](/source/radio-isotope) contamination
*[DPTA](/source/DPTA), a chelation agent used to eliminate [actinide](/source/actinide)s that have been ingested, one of three U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) radioprotectants stockpiled<ref name="cen" />
*[Prussian blue](/source/Prussian_blue)/[radiogardase](/source/radiogardase), a chelation agent to treat radio-[Cesium](/source/Cesium) and [thallium](/source/thallium) consumption, one of three the FDA radioprotectants stockpiled<ref name="cen" />
*[Potassium iodide](/source/Potassium_iodide), a [prophylactic](/source/prophylactic) drug recommended before entering [radioiodine](/source/radioiodine) environments, one of three FDA radioprotectants stockpiled<ref name="cen" />
*[Kojic acid](/source/Kojic_acid) 
*[Hyaluronan](/source/Hyaluronan)
*[Petkau effect](/source/Petkau_effect)

==References==
{{Reflist}}

Category:Radiation health effects
Category:Radiobiology
Category:Drugs with unknown mechanisms of action
Category:Experimental drugs
Category:4-Chlorophenyl compounds
Category:Sulfones
Category:Benzoates
Category:Experimental cancer drugs

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Adapted from the Wikipedia article [Ex-Rad](https://en.wikipedia.org/wiki/Ex-Rad) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Ex-Rad?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.