 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C230H299N69NA19O121P19S19 |
| Molecular Weight | 7600.76688694954 |
| Exact Mass | 7597.719 |
| CAS # | 1432726-13-0 |
| Related CAS # | Inotersen;1492984-65-2 |
| PubChem CID | 121493436 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 25 |
| Hydrogen Bond Acceptor Count | 166 |
| Rotatable Bond Count | 156 |
| Heavy Atom Count | 477 |
| Complexity | 20100 |
| Defined Atom Stereocenter Count | 70 |
| SMILES | S=P([O-])(OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OCCOC)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C(NC(C(C)=C2)=O)=O)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C(NC(C(C)=C2)=O)=O)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C(N=C(C(C)=C2)N)=O)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C(NC(C(C)=C2)=O)=O)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP([O-])(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP([O-])(OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3C(N)=NC=NC2=3)O1)OCCOC)OP([O-])(OC[C@@H]1[C@H]([C@H]([C@H](N2C(NC(C(C)=C2)=O)=O)O1)OCCOC)OP([O-])(OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C(C)=C2)N)=O)O1)OCCOC)OP([O-])(OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C(C)=C2)N)=O)O1)OCCOC)OP([O-])(OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C(C)=C2)N)=O)O1)OCCOC)O)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)O[C@@H]1[C@@H](COP([O-])(O[C@@H]2[C@@H](COP(=O)(O[C@@H]3[C@@H](COP([O-])(O[C@@H]4[C@@H](CO)O[C@H]([C@@H]4OCCOC)N4C(NC(C(C)=C4)=O)=O)=S)O[C@H]([C@@H]3OCCOC)N3C(N=C(C(C)=C3)N)=O)[S-])O[C@H]([C@@H]2OCCOC)N2C(NC(C(C)=C2)=O)=O)=S)O[C@H]([C@@H]1OCCOC)N1C(NC(C(C)=C1)=O)=O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] |
| InChi Key | QHNLHIXTRPKKQN-QKZXOKHWSA-A |
| InChi Code | InChI=1S/C230H318N69O121P19S19.19Na/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);;;;;;;;;;;;;;;;;;;/q;19*+1/p-19/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 |
| Chemical Name | nonadecasodium;1-[(2R,4S,5R)-4-[[(2R,3S,5R)-3-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-hydroxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(6-aminopurin-9-yl)-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,3R,4R,5R)-2-(hydroxymethyl)-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-sulfidophosphoryl]oxymethyl]-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | TTR mRNA levels in HepG2 cells are dose-dependently decreased by inotersen sodium (0.16–20 μM; 16 h)[1]. |
| ln Vivo | In transgenic mice carrying the Ile84Ser human TTR mutant, inotersen sodium (10–100 mg/kg; sc twice a week for 4 weeks) decreases the plasma TTR protein by >80%[1]. |
| References |
[1]. Suppressing transthyretin production in mice, monkeys and humans using 2nd-Generation antisense oligonucleotides. Amyloid. 2016 Sep;23(3):148-157. [2]. Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis. Drug Des Devel Ther. 2019 May 6;13:1515-1525. [3]. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):22-31. |
| Additional Infomation |
See also: Inotersen Sodium (annotation moved to). Drug Indication Treatment of stage 1 or Stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR). |
Solubility Data
| Solubility (In Vitro) | H2O: 100 mg/mL (13.16 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (13.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1316 mL | 0.6578 mL | 1.3157 mL | |
| 5 mM | 0.0263 mL | 0.1316 mL | 0.2631 mL | |
| 10 mM | 0.0132 mL | 0.0658 mL | 0.1316 mL |