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Systematic (IUPAC) name
2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-2'-deoxy-Pthioguanylyl-(3'→5')P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-Pthioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methylcytidine nonadecasodiumsalt
Clinical data
Trade names Kynamro
Routes of
CAS Registry Number 629167-92-6
ATC code C10AX11
PubChem CID: 44564107
ChemSpider 24710309
Chemical data
Formula C230H305N67Na19O122P19S19
Molecular mass 7594.80 g/mol

Mipomersen (previously ISIS 301012, trade name Kynamro) is a cholesterol-reducing drug. It is an antisense therapeutic that targets the messenger RNA for apolipoprotein B.[1][2][3] It is administered as a weekly injection for familial hypercholesterolemia.


Kynamro is FDA approved to treat homozygous familial hypercholesterolemia (HoFH). It reduces LDL-C, non HDL-C, and apolipoprotein B. Over a 26 week trial LDL decreased 25%. The FDA decided on a boxed warning of liver toxicity and requires cerfiication by the prescriber and pharmacy.

Mipomersen decreases hepatic and plasma apoB as well as apoC-III.[4]


The compound is a 'second-generation' antisense oligonucleotide; the nucleotides are linked with phosphorothioate linkages rather than the phosphodiester linkages of RNA and DNA, and the sugar parts are deoxyribose in the middle part of the molecule and 2'-O-methoxyethyl-modified ribose at the two ends. These modifications make the drug resistant to degradation by nucleases, allowing it to be administered weekly. The drug accumulates in the liver, which is convenient since apolipoprotein B predominantly acts there.

The complete sequence is

G*-C*-C*-U*-C*-dA-dG-dT-dC-dT-dG-dmC-dT-dT-dmC-G*-C*-A*-C*-C* [d = 2'-deoxy, * = 2'-O-(2-methoxyethyl)]

with 3'→5' phosphorothioate linkages.[5]

Phosphorothioate RNA.

Clinical development[edit]

The drug was discovered and developed to Phase 2 by ISIS Pharmaceuticals and subsequently licensed to Genzyme Corporation in 2008 by an auction bid. Isis earned an upfront payment of $325 million, with payments of a further $825 million if milestones are met.[6]

In January 2013, The United States Food and Drug Administration approved mipomersen for the treatment of homozygous familial hypercholesterolemia.[7][8] Launch quantities will be manufactured by Isis at their Carlsbad manufacturing facilities.


  1. ^ Merki E, Graham MJ, Mullick AE et al. (August 2008). "Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice". Circulation 118 (7): 743–53. doi:10.1161/CIRCULATIONAHA.108.786822. PMID 18663084. 
  2. ^ El Harchaoui K, Akdim F, Stroes ES, Trip MD, Kastelein JJ (2008). "Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins". Am J Cardiovasc Drugs 8 (4): 233–42. doi:10.2165/00129784-200808040-00003. PMID 18690757. 
  3. ^ Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP (July 2008). "Antisense technology for the prevention or the treatment of cardiovascular disease: the next blockbuster?". Expert Opin Investig Drugs 17 (7): 969–72. doi:10.1517/13543784.17.7.969. PMID 18549334. 
  4. ^ "Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins." 53. Apr 2012. pp. 784–91. doi:10.1194/jlr.P021717. PMID 22301884. 
  5. ^ Statement on a nonproprietary name adopted by the USAN council: Mipomersen sodium
  6. ^ "Genzyme and Isis Complete Licensing of Mipomersen". 24 June 2008. 
  7. ^ Pollack, Andrew (29 January 2013) F.D.A. Approves Genetic Drug to Treat Rare Disease The New York Times, Retrieved 31 January 2013
  8. ^ Staff (29 January 2013) FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder U.S. Food and Drug Administration, Retrieved 31 January 2013

External links[edit]