View source for Suramin

{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 411355479
| IUPAC_name = 8,8'-{Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]}di(1,3,5-naphthalenetrisulfonic acid)
| image = Suramin.png
| image2 = Suramin_sf.gif

<!--Clinical data-->
| tradename = Antrypol, 309 F or 309 Fourneau, Bayer 205, Moranyl, Naganin, Naganine
| pregnancy_category =  
| legal_status =  not approved by the [[US FDA]]
| routes_of_administration = injection

<!--Pharmacokinetic data-->
| bioavailability =  
| metabolism =  
| excretion =

<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 145-63-1
| ATC_prefix = P01
| ATC_suffix = CX02
| ATC_supplemental = {{ATCvet|P51|AE02}}
| PubChem = 5361
| IUPHAR_ligand = 1728
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB04786
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5168
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6032D45BEM
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C07974
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 45906
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 265502

<!--Chemical data-->
 | C=51 | H=40 | N=6 | O=23 | S=6 
| molecular_weight = 1297.29
| smiles = O=C(Nc1cc(ccc1C)C(=O)Nc3c2c(cc(cc2c(cc3)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O)c8cccc(NC(=O)Nc7cc(C(=O)Nc6cc(C(=O)Nc5c4c(cc(cc4c(cc5)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O)ccc6C)ccc7)c8
| InChI = 1/C51H40N6O23S6/c1-25-9-11-29(49(60)54-37-13-15-41(83(69,70)71)35-21-33(81(63,64)65)23-43(45(35)37)85(75,76)77)19-39(25)56-47(58)27-5-3-7-31(17-27)52-51(62)53-32-8-4-6-28(18-32)48(59)57-40-20-30(12-10-26(40)2)50(61)55-38-14-16-42(84(72,73)74)36-22-34(82(66,67)68)24-44(46(36)38)86(78,79)80/h3-24H,1-2H3,(H,54,60)(H,55,61)(H,56,58)(H,57,59)(H2,52,53,62)(H,63,64,65)(H,66,67,68)(H,69,70,71)(H,72,73,74)(H,75,76,77)(H,78,79,80)
| InChIKey = FIAFUQMPZJWCLV-UHFFFAOYAG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C51H40N6O23S6/c1-25-9-11-29(49(60)54-37-13-15-41(83(69,70)71)35-21-33(81(63,64)65)23-43(45(35)37)85(75,76)77)19-39(25)56-47(58)27-5-3-7-31(17-27)52-51(62)53-32-8-4-6-28(18-32)48(59)57-40-20-30(12-10-26(40)2)50(61)55-38-14-16-42(84(72,73)74)36-22-34(82(66,67)68)24-44(46(36)38)86(78,79)80/h3-24H,1-2H3,(H,54,60)(H,55,61)(H,56,58)(H,57,59)(H2,52,53,62)(H,63,64,65)(H,66,67,68)(H,69,70,71)(H,72,73,74)(H,75,76,77)(H,78,79,80)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FIAFUQMPZJWCLV-UHFFFAOYSA-N
}}
                     __NOTOC__
{{SI}}
{{CMG}}

==Overview==
'''Suramin''' is an antimicrobial [[medication|drug]] developed by [[Oskar Dressel]] and [[Richard Kothe]] of [[Bayer]], [[Germany]] in 1916, and is still sold by Bayer under the [[brand name]] '''Germanin'''. The formula of suramin was kept secret by Bayer for commercial reasons, however, it was elucidated and published in 1924 by [[Ernest Fourneau]] and his team of the [[Pasteur Institute]].<ref>E. Fourneau, [[Jacques Tréfouël|J. and Th. Tréfouël]] and J. Vallée (1924). "Sur une nouvelle série de médicaments trypanocides", ''C. R. Séances Acad. Sci.'' '''178''': 675.)</ref>

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref>

==Medical uses==

===Protozoa===
It is used for treatment of human [[African trypanosomiasis|sleeping sickness]] caused by [[Trypanosoma|trypanosome]]s.<ref name="pmid14728611">{{cite journal |author=Darsaud A, Chevrier C, Bourdon L, Dumas M, Buguet A, Bouteille B |title=Megazol combined with suramin improves a new diagnosis index of the early meningo-encephalitic phase of experimental African trypanosomiasis |journal=Trop. Med. Int. Health |volume=9 |issue=1 |pages=83–91 |date=January 2004 |pmid=14728611 |doi= 10.1046/j.1365-3156.2003.01154.x|url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1360-2276&date=2004&volume=9&issue=1&spage=83}}</ref>

===Helminthiasis===
It has been used in the treatment of [[onchocerciasis]].<ref name="pmid678497">{{cite journal |author=Anderson J, Fuglsang H |title=Further studies on the treatment of ocular onchocerciasis with diethylcarbamazine and suramin |journal=Br J Ophthalmol |volume=62 |issue=7 |pages=450–7 |date=July 1978 |pmid=678497 |pmc=1043255 |doi= 10.1136/bjo.62.7.450|url=http://bjo.bmj.com/cgi/pmidlookup?view=long&pmid=678497}}</ref>

===Other===
It has been investigated as treatment for [[prostate cancer]].<ref name="pmid15484217">{{cite journal |author=Ahles TA, Herndon JE, Small EJ, ''et al.'' |title=Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480 |journal=Cancer |volume=101 |issue=10 |pages=2202–8 |date=November 2004 |pmid=15484217 |doi=10.1002/cncr.20655}}</ref>

Also, suramin as treatment for [[autism]] is being evaluated<ref>http://medicalxpress.com/news/2013-03-drug-treatment-autism-symptoms-mouse.html</ref> and there are promising results in adult mice.<ref>http://news.sciencemag.org/biology/2014/06/century-old-drug-reverses-signs-autism-mice</ref><ref>http://www.nature.com/tp/journal/v4/n6/full/tp201433a.html</ref>

==Adverse reactions==
The most frequent adverse reactions are [[nausea]] and [[vomiting]]. 
About 90% of patients will get an [[urticaria]]l rash that disappears in a few days without needing to stop treatment.  There is a greater than 50% chance of [[adrenal cortex|adrenal cortical]] damage, but only a smaller proportion will require lifelong [[corticosteroid]] replacement.  It is common for patients to get a tingling or crawling sensation of the skin with suramin.  Suramin will cause clouding of the urine which is harmless: patients should be warned of this to avoid them becoming alarmed.

Kidney damage and exfoliative [[dermatitis]] occur less commonly.

Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition.<ref>{{cite journal | pmid=3548350}}</ref>

==Chemistry==
The molecular formula of suramin is C<sub>51</sub>H<sub>40</sub>N<sub>6</sub>O<sub>23</sub>S<sub>6</sub>. It is a [[symmetry|symmetric]] [[molecule]] in the center of which lies a [[urea]] (NH–CO–NH) functional group. Suramin contains eight [[benzene ring]]s, four of which are fused in pairs ([[naphthalene]]), four [[amide]] groups (in addition to the urea) and six [[sulfonic acid]] groups. When given as drug, it is usually as the sodium [[sulfonate]], with six [[sodium]] ions on the [[sulfonate]] groups rather than hydrogens.

==Research==
According to the National Cancer Institute there are no active clinical trials.<ref>Completed and closed clinical trials are listed here: [http://www.cancer.gov/search/ResultsClinicalTrialsAdvanced.aspx?protocolsearchid=4504138]</ref>

Suramin is also used in research as a broad-spectrum antagonist of [[P2 receptors]]<ref name="pmid16968944">{{cite journal |author=Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA. |title=International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy |journal=Pharmacol Rev. |volume=58 |issue=3 |pages=281–341 |date=September 2006 |pmid=16968944 |doi=10.1124/pr.58.3.3 |pmc=3471216}}</ref><ref name="pmid11171941">{{cite journal |author=Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Séguéla P, Voigt M, Humphrey PP. |title=International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits |journal=Pharmacol Rev. |volume=53 |issue=1 |pages=107–118 |date=March 2001 |pmid=11171941}}</ref> and agonist of [[Ryanodine receptor]]s.<ref name="pmid16056233">{{cite journal |author=Wolner I, Kassack MU, Ullmann H, Karel A, Hohenegger M |title=Use-dependent inhibition of the skeletal muscle ryanodine receptor by the suramin analogue NF676 |journal=Br. J. Pharmacol. |volume=146 |issue=4 |pages=525–33 |date=October 2005 |pmid=16056233 |pmc=1751178 |doi=10.1038/sj.bjp.0706359}}</ref>

Its effect on [[telomerase]] has been investigated.<ref name="pmid18667993">{{cite journal |author=Erguven M, Akev N, Ozdemir A, Karabulut E, Bilir A |title=The inhibitory effect of suramin on telomerase activity and spheroid growth of C6 glioma cells |journal=Med. Sci. Monit. |volume=14 |issue=8 |pages=BR165–73 |date=August 2008 |pmid=18667993 |doi= |url=http://www.medscimonit.com/fulltxt.php?ICID=865765}}</ref>

It may have some activity against RNA viruses.<ref name=Mastrangelo2012>Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M (2012) Structure-based inhibition of norovirus RNA-dependent RNA-polymerases. J Mol Biol</ref>

In addition to antagonism of P2 receptors, Suramin inhibits the activation of heterotrimeric G proteins in a variety of other GPCRs with varying potency.  It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF).  With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including [[rhodopsin]], the [[A1 adenosine receptor]], and the [[D2 dopamine receptor]].<ref name="pmid8700151">{{cite journal |author=Beindl W, Mitterauer T, Hohenegger M, Ijzerman AP, Nanoff C, Freissmuth M. |title=Inhibition of receptor/G protein coupling by suramin analogues |journal=ol. Pharmacology. |volume=50 |issue=2 |pages=415–23 |date=August 1996 |pmid=8700151 |doi= |url=http://molpharm.aspetjournals.org/content/50/2/415.long}}</ref>

==References==
{{Reflist|2}}

== External links ==
* [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=SVR Suramin bound to proteins] in the [[Protein Data Bank|PDB]]
* [http://www.drugs.com/cons/Suramin.html Drug information]
* [http://www.jbc.org/cgi/content/full/273/20/12281 Suramin, drug information by JBC Online]
* [http://www.clinicaltrials.gov/ct/show/NCT00006476?order=11 Suramin in treating patients with recurrent bladder cancer]
* [http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=40052 National Cancer Institute]


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