Mipomersen sodiumProduct ingredient for Mipomersen

Show full entry for Mipomersen
Name
Mipomersen sodium
Drug Entry
Mipomersen

Mipomersen sodium, which was known as the investigational drug, isis-301012, is the salt form of a synthetic phosphorothioate oligonucleotide. Mipomersen sodium prevents the formation of apo B-100, resulting in a decrease in the levels of apolipoprotein B (apo B), low density lipoprotein (LDL), and total cholesterol. Mipomersen is indicated in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications. It is marketed under the brand name Kynamro in the United States, and the FDA label includes a black box warning of hepatoxicity. Specifically, elevations in the liver enzymes, i.e. transaminases, and in liver fat (hepatic steatosis) have been reported. Due to this serious risk of liver toxicity, mipomersen sodium is only available to patients under the restricted program called Kynamro Risk Evaluation and Mitigation Strategy program.

See full entry for Mipomersen
Accession Number
DBSALT000120
Structure
Similar Structures
Synonyms
Mipomersen sodium
UNII
18EAY4870E
CAS Number
629167-92-6
Weight
Average: 7594.76
Monoisotopic: 7589.74862332
Chemical Formula
C230H305N67Na19O122P19S19
InChI Key
OSGPYAHSKOGBFY-KMHHXCEHSA-A
InChI
InChI=1S/C230H324N67O122P19S19.19Na/c1-97-55-278(217(309)256-177(97)231)141-45-131(112(400-141)70-381-422(327,328)442-136-50-146(283-66-108(12)196(302)275-228(283)320)406-118(136)76-387-427(337,338)448-140-54-150(294-93-253-154-191(294)266-214(243)270-200(154)306)409-120(140)78-389-428(339,340)446-138-52-148(292-91-250-151-186(240)246-89-248-188(151)292)407-121(138)79-390-430(343,344)450-169-124(413-204(160(169)373-37-27-363-17)286-59-101(5)181(235)260-221(286)313)83-394-435(353,354)455-174-128(417-209(165(174)378-42-32-368-22)291-68-110(14)198(304)277-230(291)322)87-396-434(351,352)453-172-126(415-207(163(172)376-40-30-366-20)289-62-104(8)184(238)263-224(289)316)85-395-433(349,350)452-171-123(412-206(162(171)375-39-29-365-19)288-61-103(7)183(237)262-223(288)315)82-393-432(347,348)449-168-111(69-298)410-211(159(168)372-36-26-362-16)296-95-254-155-192(296)267-215(244)271-201(155)307)439-420(323,324)384-74-117-137(51-147(405-117)284-67-109(13)197(303)276-229(284)321)444-425(333,334)388-77-119-139(53-149(408-119)293-92-252-153-190(293)265-213(242)269-199(153)305)447-426(335,336)386-71-113-132(46-142(401-113)279-56-98(2)178(232)257-218(279)310)440-421(325,326)383-73-115-135(49-145(403-115)282-65-107(11)195(301)274-227(282)319)443-424(331,332)385-75-116-134(48-144(404-116)281-64-106(10)194(300)273-226(281)318)441-423(329,330)382-72-114-133(47-143(402-114)280-57-99(3)179(233)258-219(280)311)445-429(341,342)392-81-129-176(167(380-44-34-370-24)212(419-129)297-96-255-156-193(297)268-216(245)272-202(156)308)457-438(359,360)398-86-127-173(164(377-41-31-367-21)208(416-127)290-63-105(9)185(239)264-225(290)317)454-436(355,356)399-88-130-175(166(379-43-33-369-23)210(418-130)295-94-251-152-187(241)247-90-249-189(152)295)456-437(357,358)397-84-125-170(161(374-38-28-364-18)205(414-125)287-60-102(6)182(236)261-222(287)314)451-431(345,346)391-80-122-157(299)158(371-35-25-361-15)203(411-122)285-58-100(4)180(234)259-220(285)312;;;;;;;;;;;;;;;;;;;/h55-68,89-96,111-150,157-176,203-212,298-299H,25-54,69-88H2,1-24H3,(H,323,324)(H,325,326)(H,327,328)(H,329,330)(H,331,332)(H,333,334)(H,335,336)(H,337,338)(H,339,340)(H,341,342)(H,343,344)(H,345,346)(H,347,348)(H,349,350)(H,351,352)(H,353,354)(H,355,356)(H,357,358)(H,359,360)(H2,231,256,309)(H2,232,257,310)(H2,233,258,311)(H2,234,259,312)(H2,235,260,313)(H2,236,261,314)(H2,237,262,315)(H2,238,263,316)(H2,239,264,317)(H2,240,246,248)(H2,241,247,249)(H,273,300,318)(H,274,301,319)(H,275,302,320)(H,276,303,321)(H,277,304,322)(H3,242,265,269,305)(H3,243,266,270,306)(H3,244,267,271,307)(H3,245,268,272,308);;;;;;;;;;;;;;;;;;;/q;19*+1/p-19/t111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122+,123-,124-,125+,126-,127+,128-,129-,130+,131+,132+,133+,134+,135+,136+,137+,138+,139+,140+,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,157+,158+,159-,160-,161+,162-,163-,164+,165-,166+,167-,168-,169-,170+,171-,172-,173+,174-,175+,176-,203+,204-,205+,206-,207-,208+,209-,210+,211-,212-;;;;;;;;;;;;;;;;;;;/m1.................../s1
IUPAC Name
nonadecasodium [(2S,3S,4S,5S)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxy-4-(2-methoxyethoxy)oxolan-2-yl]methyl {[(2S,3S,4R,5S)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2S,3S,4R,5S)-2-{[({[(2S,3S,4R,5S)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3R,4S,5R)-2-{[({[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3S,5R)-2-{[({[(2R,3R,4S,5R)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3R,4S,5R)-2-{[({[(2R,3R,4S,5R)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3R,4S,5R)-5-(4-amino-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-2-{[({[(2R,3R,4S,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(6-amino-9H-purin-9-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-5-(6-amino-9H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}(oxido)phosphoryl)oxy]methyl}-4-(2-methoxyethoxy)oxolan-3-yl]sulfanyl}phosphonate
SMILES
[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].COCCO[C@H]1[C@@H](O)[C@H](COP([O-])(=O)S[C@H]2[C@H](COP([O-])(=O)S[C@H]3[C@H](COP([O-])(=O)S[C@H]4[C@H](COP([O-])(=O)S[C@@H]5[C@@H](COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@H]6C[C@@H](O[C@@H]6COP([O-])(=O)S[C@@H]6[C@@H](COP([O-])(=O)S[C@@H]7[C@@H](COP([O-])(=O)S[C@@H]8[C@@H](COP([O-])(=O)S[C@@H]9[C@@H](COP([O-])(=O)S[C@@H]%10[C@@H](CO)O[C@H]([C@@H]%10OCCOC)N%10C=NC%11=C%10N=C(N)NC%11=O)O[C@H]([C@@H]9OCCOC)N9C=C(C)C(N)=NC9=O)O[C@H]([C@@H]8OCCOC)N8C=C(C)C(N)=NC8=O)O[C@H]([C@@H]7OCCOC)N7C=C(C)C(=O)NC7=O)O[C@H]([C@@H]6OCCOC)N6C=C(C)C(N)=NC6=O)N6C=NC7=C6N=CN=C7N)N6C=NC7=C6N=C(N)NC7=O)N6C=C(C)C(=O)NC6=O)N6C=C(C)C(N)=NC6=O)N6C=C(C)C(=O)NC6=O)N6C=NC7=C6N=C(N)NC7=O)N6C=C(C)C(N)=NC6=O)N6C=C(C)C(=O)NC6=O)N6C=C(C)C(=O)NC6=O)N6C=C(C)C(N)=NC6=O)O[C@H]([C@@H]5OCCOC)N5C=NC6=C5N=C(N)NC6=O)O[C@@H]([C@H]4OCCOC)N4C=C(C)C(N)=NC4=O)O[C@@H]([C@H]3OCCOC)N3C=NC4=C3N=CN=C4N)O[C@@H]([C@H]2OCCOC)N2C=C(C)C(N)=NC2=O)O[C@@H]1N1C=C(C)C(N)=NC1=O
PubChem Compound
44564107
ChemSpider
24710309
ChEMBL
CHEMBL502097
Wikipedia
Mipomersen
Predicted Properties
PropertyValueSource
logP-9.4Chemaxon
pKa (Strongest Acidic)1.28Chemaxon
Physiological Charge-5Chemaxon
Hydrogen Acceptor Count141Chemaxon
Hydrogen Donor Count26Chemaxon
Polar Surface Area2603.2 Å2Chemaxon
Rotatable Bond Count156Chemaxon
Refractivity1578.06 m3·mol-1Chemaxon
Polarizability645.59 Å3Chemaxon
Number of Rings46Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon