Miravirsen

Miravirsen
Clinical data
Other namesSPC3649
Routes of
administration		Intravenous or subcutaneous injection
ATC code
  • none
Legal status
Legal status
  • Investigational
Identifiers
  • all-P-ambo-5-methyl-2′-O,4′-C-methylene-P-thiocytidylyl-(3′→5′)-2′- deoxy-P-thiocytidylyl-(3′→5′)-2′-O,4′-C-methylene-P-thioadenylyl- (3′→5′)-P-thiothymidylyl-(3′→5′)-P-thiothymidylyl-(3′→5′)-2′-O,4′-C- methylene-P-thioguanylyl-(3′→5′)-5-methyl-2′-O,4′-C-methylene-P- thiouridylyl-(3′→5′)-2′-deoxy-P-thiocytidylyl-(3′→5′)-2′-deoxy-P- thioadenylyl-(3′→5′)-5-methyl-2′-O,4′-C-methylene-P-thiocytidylyl-(3′→5′)-2′-deoxy-P-thioadenylyl-(3′→5′)-5-methyl-2′-O,4′-C-methylene-P-thiocytidylyl-(3′→5′)-P-thiothymidylyl-(3′→5′)-5-methyl- 2′-O,4′-C-methylene-P-thiocytidylyl-(3′→5′)-5-methyl-2′-O,4′-C-methylenecytidine
CAS Number
PubChem CID
UNII
Chemical and physical data
FormulaC156H195N49O83P14S14
Molar mass4967.01 g·mol−1
  • CC=1C(=NC(N([C@H]2[C@@H]3OC[C@]([C@H]3OP(=S)(O)OC[C@@H]3[C@H](C[C@@H](O3)N3C(=O)N=C(N)C=C3)OP(=S)(O)OC[C@]34[C@H]([C@H]([C@@H](O3)N3C=NC=5C(N)=NC=NC35)OC4)OP(=S)(O)OC[C@@H]4[C@H](C[C@@H](O4)N4C(=O)NC(=O)C(C)=C4)OP(=S)(O)OC[C@@H]4[C@H](C[C@@H](O4)N4C(=O)NC(=O)C(C)=C4)OP(=S)(O)OC[C@]43[C@H]([C@H]([C@@H](O4)N4C=NC=5C(=O)NC(N)=NC45)OC3)OP(=S)(O)OC[C@]34[C@H]([C@H]([C@@H](O3)N3C(=O)NC(=O)C(=C3)C)OC4)OP(=S)(O)OC[C@@H]4[C@H](C[C@@H](O4)N4C(=O)N=C(N)C=C4)OP(=S)(O)OC[C@@H]4[C@H](C[C@@H](O4)N4C=NC=3C(N)=NC=NC43)OP(=S)(O)OC[C@]43[C@H]([C@H]([C@@H](O4)N4C(=O)N=C(N)C(=C4)C)OC3)OP(=S)(O)OC[C@@H]3[C@H](C[C@@H](O3)N3C=NC=4C(N)=NC=NC34)OP(=S)(O)OC[C@]34[C@H]([C@H]([C@@H](O3)N3C(=O)N=C(N)C(=C3)C)OC4)OP(=S)(O)OC[C@@H]4[C@H](C[C@@H](O4)N4C(=O)NC(=O)C(C)=C4)OP(=S)(O)OC[C@]43[C@H]([C@H]([C@@H](O4)N4C(=O)N=C(N)C(=C4)C)OC3)OP(=S)(O)OC[C@]34[C@H]([C@H]([C@@H](O3)N3C(=O)N=C(N)C(=C3)C)OC4)O)(CO)O2)C1)=O)N
  • InChI=1S/C156H195N49O83P14S14/c1-60-21-196(140(215)180-112(60)159)129-96-104(207)150(268-129,39-238-96)46-253-301(236,315)287-109-101-133(200-25-64(5)116(163)184-144(200)219)271-153(109,42-243-101)49-256-297(232,311)279-73-18-89(195-28-67(8)126(210)189-147(195)222)264-80(73)35-251-293(228,307)283-106-98-131(198-23-62(3)114(161)182-142(198)217)269-151(106,40-240-98)48-255-300(235,314)281-75-20-91(203-57-175-93-118(165)169-54-172-121(93)203)266-82(75)36-252-294(229,308)284-107-99-132(199-24-63(4)115(162)183-143(199)218)270-152(107,41-241-99)47-254-299(234,313)280-74-19-90(202-56-174-92-117(164)168-53-171-120(92)202)265-81(74)31-247-289(224,303)275-69-14-85(191-12-10-83(157)178-138(191)213)260-76(69)32-249-292(227,306)285-108-100-134(201-29-68(9)127(211)190-148(201)223)272-154(108,43-242-100)52-259-302(237,316)288-111-103-136(205-59-177-95-123(205)185-137(167)186-128(95)212)274-156(111,45-245-103)51-258-298(233,312)278-72-17-88(194-27-66(7)125(209)188-146(194)221)262-78(72)30-246-290(225,304)276-71-16-87(193-26-65(6)124(208)187-145(193)220)263-79(71)34-250-295(230,309)286-110-102-135(204-58-176-94-119(166)170-55-173-122(94)204)273-155(110,44-244-102)50-257-296(231,310)277-70-15-86(192-13-11-84(158)179-139(192)214)261-77(70)33-248-291(226,305)282-105-97-130(267-149(105,37-206)38-239-97)197-22-61(2)113(160)181-141(197)216/h10-13,21-29,53-59,69-82,85-91,96-111,129-136,206-207H,14-20,30-52H2,1-9H3,(H,224,303)(H,225,304)(H,226,305)(H,227,306)(H,228,307)(H,229,308)(H,230,309)(H,231,310)(H,232,311)(H,233,312)(H,234,313)(H,235,314)(H,236,315)(H,237,316)(H2,157,178,213)(H2,158,179,214)(H2,159,180,215)(H2,160,181,216)(H2,161,182,217)(H2,162,183,218)(H2,163,184,219)(H2,164,168,171)(H2,165,169,172)(H2,166,170,173)(H,187,208,220)(H,188,209,221)(H,189,210,222)(H,190,211,223)(H3,167,185,186,212)/t69-,70-,71-,72-,73-,74-,75-,76+,77+,78+,79+,80+,81+,82+,85+,86+,87+,88+,89+,90+,91+,96+,97+,98+,99+,100+,101+,102+,103+,104-,105-,106-,107-,108-,109-,110-,111-,129+,130+,131+,132+,133+,134+,135+,136+,149-,150+,151+,152+,153+,154+,155+,156+,289?,290?,291?,292?,293?,294?,295?,296?,297?,298?,299?,300?,301?,302?/m0/s1
  • Key:RJUXZHVRDPBRSK-HZOZQJTBSA-N

Miravirsen (INN; codenamed SPC3649) is an experimental drug for the treatment of hepatitis C, being developed by Santaris Pharma. As of 2017 it was in Phase II clinical trials.[1]

Miravirsen had been given by subcutaneous injection in early clinical trials as of 2017.[1] It is antisense to a human microRNA called miR-122. miR-122 ferries an argonaute protein to 5'-UTR region of viral RNA, where it binds, protecting the RNA from being destroyed by normally present nucleases; by binding to miR-122, miravirsen removes that protection and the virus RNA can be destroyed.[1] There is some evidence that the 5'-UTR region mutates under repeated exposure to miravirsen.[1]

Chemistry

Miravirsen is a modified antisense oligonucleotide consisting of a chain of 15 nucleotides, the base sequence of which is designed to selectively bind to miR-122.[1][2] Seven of the 15 sugar units are deoxyriboses, and the other eight are riboses with an additional bridge between the 2' oxygen and the 4' carbon atoms; this makes miravirsen a locked nucleic acid gapmer. Furthermore, miravirsen uses phosphorothioate linkages instead of the phosphate linkages in natural oligonucleotides to make it stable towards degradation by nucleases.[2]

The complete base sequence is

mC*-dC-A*-dT-dT-G*-mU*-dC-dA-mC*-dA-mC*-dT-mC*-mC* [d = 2'-deoxy, m = 5-methyl, * = 2'-O,4'-C-methylene, i.e. bridged or "locked" sugar]

with 3'→5' phosphorothioate linkages.[2]

References

  1. ^ a b c d e Titze-de-Almeida R, David C, Titze-de-Almeida SS (July 2017). "The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market". Pharmaceutical Research. 34 (7): 1339–1363. doi:10.1007/s11095-017-2134-2. PMID 28389707. S2CID 4925216.
  2. ^ a b c "Miravirsen". PubChem.

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