inotersen   Click here for help

GtoPdb Ligand ID: 13543

Synonyms: GSK-2998728 | GSK2998728 | ISIS-420915 | ISIS420915 | Tegsedi®
Approved drug
inotersen is an approved drug (EMA & FDA (2018), UK MHRA (2021))
Compound class: Nucleic acid
Comment: Inotersen is an antisense oligonucleotide that blocks expression of mutant transthyretin (TTR) protein that form pathogenic deposits in patients with hereditary transthyretin-mediated amyloidosis (hATTR).
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC1=CN([C@H]2C[C@@H]([C@@H](COP(=S)(O)O[C@H]3C[C@H](N4C=NC5=C4N=CN=C5N)O[C@@H]3COP(=S)(O)O[C@H]6C[C@H](N7C=C(C)C(=O)NC7=O)O[C@@H]6COP(=S)(O)O[C@H]8C[C@H](N9C=C(C)C(=O)NC9=O)O[C@@H]8COP(=S)(O)O[C@H]%10C[C@H](N%11C=NC%12=C%11N=C(N)NC%12=O)O[C@@H]%10COP(=S)(O)O[C@@H]%13[C@@H](COP(=S)(O)O[C@@H]%14[C@@H](COP(=S)(O)O[C@@H]%15[C@@H](COP(=S)(O)O[C@@H]%16[C@@H](COP(=S)(O)O[C@@H]%17[C@@H](CO)O[C@H]([C@@H]%17OCCOC)N%18C=C(C)C(=O)NC%18=O)O[C@H]([C@@H]%16OCCOC)N%19C=C(C)C(=NC%19=O)N)O[C@H]([C@@H]%15OCCOC)N%20C=C(C)C(=O)NC%20=O)O[C@H]([C@@H]%14OCCOC)N%21C=C(C)C(=O)NC%21=O)O[C@H]([C@@H]%13OCCOC)N%22C=NC%23=C%22N=C(N)NC%23=O)O2)OP(=S)(O)OC[C@@H]%24[C@H](C[C@H](N%25C=NC%26=C%25N=CN=C%26N)O%24)OP(=S)(O)OC[C@@H]%27[C@H](C[C@H](N%28C=C(C)C(=O)NC%28=O)O%27)OP(=S)(O)OC[C@@H]%29[C@H](C[C@H](N%30C=NC%31=C%30N=C(N)NC%31=O)O%29)OP(=S)(O)OC[C@@H]%32[C@H](C[C@H](N%33C=NC%34=C%33N=CN=C%34N)O%32)OP(=S)(O)OC[C@@H]%35[C@H](C[C@H](N%36C=NC%37=C%36N=CN=C%37N)O%35)OP(=S)(O)OC[C@@H]%38[C@H]([C@H]([C@H](N%39C=NC%40=C%39N=CN=C%40N)O%38)OCCOC)OP(=S)(O)OC[C@@H]%41[C@H]([C@H]([C@H](N%42C=C(C)C(=O)NC%42=O)O%41)OCCOC)OP(=S)(O)OC[C@@H]%43[C@H]([C@H]([C@H](N%44C=C(C)C(=NC%44=O)N)O%43)OCCOC)OP(=S)(O)OC[C@@H]%45[C@H]([C@H]([C@H](N%46C=C(C)C(=NC%46=O)N)O%45)OCCOC)OP(=S)(O)OC[C@@H]%47[C@H]([C@H]([C@H](N%48C=C(C)C(=NC%48=O)N)O%47)OCCOC)O)C(=O)N=C1N
Isomeric SMILES CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)COP(=S)(O)O[C@H]3C[C@@H](O[C@@H]3COP(=S)(O)O[C@H]4C[C@@H](O[C@@H]4COP(=S)(O)O[C@@H]5[C@H](O[C@H]([C@@H]5OCCOC)N6C=NC7=C6N=C(NC7=O)N)COP(=S)(O)O[C@@H]8[C@H](O[C@H]([C@@H]8OCCOC)N9C=C(C(=O)NC9=O)C)COP(=S)(O)O[C@@H]%10[C@H](O[C@H]([C@@H]%10OCCOC)N%11C=C(C(=O)NC%11=O)C)COP(=S)(O)O[C@@H]%12[C@H](O[C@H]([C@@H]%12OCCOC)N%13C=C(C(=NC%13=O)N)C)COP(=S)(O)O[C@@H]%14[C@H](O[C@H]([C@@H]%14OCCOC)N%15C=C(C(=O)NC%15=O)C)CO)N%16C=NC%17=C%16N=C(NC%17=O)N)N%18C=C(C(=O)NC%18=O)C)OP(=S)(O)OC[C@@H]%19[C@H](C[C@@H](O%19)N%20C=NC%21=C(N=CN=C%21%20)N)OP(=S)(O)OC[C@@H]%22[C@H](C[C@@H](O%22)N%23C=C(C(=NC%23=O)N)C)OP(=S)(O)OC[C@@H]%24[C@H](C[C@@H](O%24)N%25C=NC%26=C(N=CN=C%26%25)N)OP(=S)(O)OC[C@@H]%27[C@H](C[C@@H](O%27)N%28C=C(C(=O)NC%28=O)C)OP(=S)(O)OC[C@@H]%29[C@H](C[C@@H](O%29)N%30C=NC%31=C%30N=C(NC%31=O)N)OP(=S)(O)OC[C@@H]%32[C@H](C[C@@H](O%32)N%33C=NC%34=C(N=CN=C%34%33)N)OP(=S)(O)OC[C@@H]%35[C@H](C[C@@H](O%35)N%36C=NC%37=C(N=CN=C%37%36)N)OP(=S)(O)OC[C@@H]%38[C@H]([C@H]([C@@H](O%38)N%39C=NC%40=C(N=CN=C%40%39)N)OCCOC)OP(=S)(O)OC[C@@H]%41[C@H]([C@H]([C@@H](O%41)N%42C=C(C(=O)NC%42=O)C)OCCOC)OP(=S)(O)OC[C@@H]%43[C@H]([C@H]([C@@H](O%43)N%44C=C(C(=NC%44=O)N)C)OCCOC)OP(=S)(O)OC[C@@H]%45[C@H]([C@H]([C@@H](O%45)N%46C=C(C(=NC%46=O)N)C)OCCOC)OP(=S)(O)OC[C@@H]%47[C@H]([C@H]([C@@H](O%47)N%48C=C(C(=NC%48=O)N)C)OCCOC)O
InChI InChI=1S/C230H318N69O121P19S19/c1-98-53-280(219(312)262-178(98)231)140-43-110(121(382-140)66-364-425(328,444)406-114-47-144(292-90-254-150-183(236)244-85-249-188(150)292)387-126(114)71-368-423(326,442)404-112-45-142(282-59-104(7)197(303)274-225(282)318)383-122(112)67-363-421(324,440)403-111-44-141(281-58-103(6)196(302)273-224(281)317)385-124(111)69-366-427(330,446)410-119-52-149(297-95-260-156-194(297)268-217(242)271-204(156)310)391-130(119)75-372-431(334,450)419-167-139(401-215(177(167)362-42-32-352-22)299-97-261-157-195(299)269-218(243)272-205(157)311)84-381-438(341,457)418-165-136(398-213(175(165)360-40-30-350-20)291-64-109(12)202(308)279-230(291)323)82-379-437(340,456)417-163-135(397-211(173(163)358-38-28-348-18)289-62-107(10)200(306)277-228(289)321)81-378-435(338,454)414-161-132(394-209(171(161)356-36-26-346-16)286-56-101(4)181(234)265-222(286)315)78-375-433(336,452)412-159-120(65-300)392-207(169(159)354-34-24-344-14)288-61-106(9)199(305)276-227(288)320)402-422(325,441)367-70-125-115(48-145(386-125)293-91-255-151-184(237)245-86-250-189(151)293)407-426(329,445)365-68-123-113(46-143(384-123)283-60-105(8)198(304)275-226(283)319)405-424(327,443)371-74-129-118(51-148(390-129)296-94-259-155-193(296)267-216(241)270-203(155)309)409-429(332,448)370-72-127-116(49-146(388-127)294-92-256-152-185(238)246-87-251-190(152)294)408-428(331,447)369-73-128-117(50-147(389-128)295-93-257-153-186(239)247-88-252-191(153)295)411-430(333,449)374-77-138-166(176(361-41-31-351-21)214(400-138)298-96-258-154-187(240)248-89-253-192(154)298)420-439(342,458)380-83-137-164(174(359-39-29-349-19)212(399-137)290-63-108(11)201(307)278-229(290)322)416-436(339,455)377-80-134-162(172(357-37-27-347-17)210(396-134)287-57-102(5)182(235)266-223(287)316)415-434(337,453)376-79-133-160(170(355-35-25-345-15)208(395-133)285-55-100(3)180(233)264-221(285)314)413-432(335,451)373-76-131-158(301)168(353-33-23-343-13)206(393-131)284-54-99(2)179(232)263-220(284)313/h53-64,85-97,110-149,158-177,206-215,300-301H,23-52,65-84H2,1-22H3,(H,324,440)(H,325,441)(H,326,442)(H,327,443)(H,328,444)(H,329,445)(H,330,446)(H,331,447)(H,332,448)(H,333,449)(H,334,450)(H,335,451)(H,336,452)(H,337,453)(H,338,454)(H,339,455)(H,340,456)(H,341,457)(H,342,458)(H2,231,262,312)(H2,232,263,313)(H2,233,264,314)(H2,234,265,315)(H2,235,266,316)(H2,236,244,249)(H2,237,245,250)(H2,238,246,251)(H2,239,247,252)(H2,240,248,253)(H,273,302,317)(H,274,303,318)(H,275,304,319)(H,276,305,320)(H,277,306,321)(H,278,307,322)(H,279,308,323)(H3,241,267,270,309)(H3,242,268,271,310)(H3,243,269,272,311)/t110-,111-,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+,158+,159+,160+,161+,162+,163+,164+,165+,166+,167+,168+,169+,170+,171+,172+,173+,174+,175+,176+,177+,206+,207+,208+,209+,210+,211+,212+,213+,214+,215+,421?,422?,423?,424?,425?,426?,427?,428?,429?,430?,431?,432?,433?,434?,435?,436?,437?,438?,439?/m0/s1
InChI Key KLEGMTRDCCDFJK-XDQSQZFTSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Designated as an orphan medicine by the EMA in spring 2014. Approved by the EMA and FDA in 2018 to treat stage1/2 hereditary transthyretin-mediated amyloid polyneuropathy.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04136184 NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy Phase 3 Interventional Ionis Pharmaceuticals, Inc.
NCT01737398 Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy Phase 2/Phase 3 Interventional Ionis Pharmaceuticals, Inc.
NCT02175004 Extension Study Assessing Long Term Safety and Efficacy of IONIS-TTR Rx in Familial Amyloid Polyneuropathy (FAP) Phase 3 Interventional Ionis Pharmaceuticals, Inc. 1-2
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com