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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
miR-122[1]
miR-122 (microRNA-122). |
|---|---|
| ln Vitro |
Miravirsen's primary mechanism of action is assumed to be hybridizing to mature miR-122 and preventing its interaction with HCV RNA; both pri- and pre-miR-122 include its target sequence[1]. With nanomolar affinity, miravirsen binds to the stem-loop structure of pri- and pre-miR-122, preventing Drosha and Dicer from processing miR-122 precursors[1].
Miravirsen hybridizes to mature miR-122 with high affinity (Tm >80degC) and blocks its interaction with HCV RNA; it inhibits HCV replication across genotypes 1-6 in cell-based assays; ED50 is approximately 2.2 log10 HCV RNA reduction at 5 mg/kg in preclinical models. |
| ln Vivo |
In mice, miravirsen (SPC-3649; 2.5–25 mg/kg; intravenous; daily, for 3 days) suppresses miR-122 activity[2].
Miravirsen demonstrates potent antiviral activity in a Phase 2a clinical trial: dose-dependent reduction in HCV RNA levels was observed in treatment-naïve chronic HCV patients, with viral load reductions becoming significant by the third dose and persisting for weeks to months post-dosing. |
| Enzyme Assay |
miR-122 binding affinity is assessed by surface plasmon resonance (SPR) or electrophoretic mobility shift assay (EMSA) using synthetic miR-122 RNA and LNA antisense oligonucleotide; thermal denaturation experiments measure melting temperature (Tm) to evaluate duplex stability.
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| Cell Assay |
HCV replication inhibition is evaluated in Huh7.5 human hepatoma cells infected with HCV replicon or JFH1-based recombinant viruses; cells are treated with Miravirsen for 48-72 hours, and HCV RNA levels are quantified by qRT-PCR; EC50 values are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: NMRI female mice (27 g)[2]
Doses: 2.5, 6.25, 12.5, and 25 mg/kg Route of Administration: intravenous (iv)injection; daily, for 3 days Experimental Results: Inhibited miR-122 activity in a dose-dependent manner. Mouse models: transgenic mice expressing HCV replicon or humanized liver mice (e.g., uPA-SCID) infected with HCV are administered Miravirsen via subcutaneous injection; HCV RNA levels in plasma and liver are measured; tolerability and pharmacokinetics are assessed. |
| ADME/Pharmacokinetics |
PK: subcutaneous administration; well-characterized clinical PK with a plasma half-life (t½) of approximately 4 days; predominantly distributed to liver (the target organ); metabolized by nuclease degradation; excreted in urine; dose-proportional exposure with minimal accumulation.
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| Toxicity/Toxicokinetics |
Toxicology: Phase 1 and Phase 2a clinical trials demonstrate acceptable safety profile; most adverse events were mild to moderate; no dose-limiting toxicity reported; no significant effects on liver function or lipid metabolism; long-term safety remains to be fully characterized.
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| References |
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| Additional Infomation |
Miravirsen has been investigated for the treatment of hepatitis C and chronic hepatitis C.
Miravirsen completed Phase 2a clinical trials for HCV infection, demonstrating proof-of-concept antiviral efficacy; however, further development was not advanced to Phase 3; it was not approved by FDA or EMA; it remains a valuable research tool for miR-122 biology and HCV research; its well-characterized clinical PK and safety profile make it a benchmark for next-generation miR-122 inhibitor development. |
| Molecular Formula |
C151H185N49O83P14S14
|
|---|---|
| Molecular Weight |
4896.90576338768
|
| Exact Mass |
4894.421
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| CAS # |
1072874-90-8
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| PubChem CID |
56843415
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
-12.2
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| Hydrogen Bond Donor Count |
32
|
| Hydrogen Bond Acceptor Count |
111
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| Rotatable Bond Count |
86
|
| Heavy Atom Count |
311
|
| Complexity |
14200
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S=P(O)(OCC12COC(C(N3C(NC(C(C)=C3)=O)=O)O1)C2OP(O)(OCC1C(CC(N2C(N=C(C=C2)N)=O)O1)OP(O)(OCC1C(CC(N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OCC12COC(C(N3C(N=C(C=C3)N)=O)O1)C2OP(O)(OCC1C(CC(N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OCC12COC(C(N3C(N=C(C=C3)N)=O)O1)C2OP(O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OCC12COC(C(N3C(N=C(C=C3)N)=O)O1)C2OP(O)(OCC12COC(C(N3C(N=C(C=C3)N)=O)O1)C2O)=S)=S)=S)=S)=S)=S)=S)=S)OC1C2C(N3C=NC4C(NC(N)=NC3=4)=O)OC1(COP(O)(OC1CC(N3C(NC(C(C)=C3)=O)=O)OC1COP(O)(OC1CC(N3C(NC(C(C)=C3)=O)=O)OC1COP(O)(OC1C3C(N4C=NC5C(N)=NC=NC4=5)OC1(COP(O)(OC1CC(N4C(N=C(C=C4)N)=O)OC1COP(O)(OC1C4C(N5C(N=C(C=C5)N)=O)OC1(CO)CO4)=S)=S)CO3)=S)=S)=S)CO2
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| InChi Key |
OSOOBMBDIGGTCP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C151H185N49O83P14S14/c1-60-26-193(140(215)182-119(60)203)87-21-66(74(258-87)34-245-290(225,304)281-110-102-130(199-58-171-94-114(161)165-55-168-117(94)199)268-150(110,44-239-102)50-252-291(226,305)272-65-20-86(187-13-6-79(153)174-134(187)209)256-72(65)33-243-286(221,300)277-105-97-125(262-144(105,37-201)38-234-97)189-15-8-81(155)176-136(189)211)271-285(220,299)241-30-73-67(22-88(257-73)194-27-61(2)120(204)183-141(194)216)273-293(228,307)253-51-151-45-240-103(131(269-151)200-59-172-95-118(200)180-132(162)181-123(95)207)111(151)283-297(232,311)254-52-149-43-238-101(129(267-149)196-29-63(4)122(206)185-143(196)218)109(149)280-289(224,303)244-32-71-64(19-85(255-71)186-12-5-78(152)173-133(186)208)270-284(219,298)242-31-76-69(24-90(260-76)197-56-169-92-112(159)163-53-166-115(92)197)275-294(229,308)249-47-147-41-236-99(127(265-147)191-17-10-83(157)178-138(191)213)107(147)279-288(223,302)247-36-77-70(25-91(261-77)198-57-170-93-113(160)164-54-167-116(93)198)276-295(230,309)250-48-146-40-235-98(126(264-146)190-16-9-82(156)177-137(190)212)106(146)278-287(222,301)246-35-75-68(23-89(259-75)195-28-62(3)121(205)184-142(195)217)274-292(227,306)251-49-148-42-237-100(128(266-148)192-18-11-84(158)179-139(192)214)108(148)282-296(231,310)248-46-145-39-233-96(104(145)202)124(263-145)188-14-7-80(154)175-135(188)210/h5-18,26-29,53-59,64-77,85-91,96-111,124-131,201-202H,19-25,30-52H2,1-4H3,(H,219,298)(H,220,299)(H,221,300)(H,222,301)(H,223,302)(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)(H2,152,173,208)(H2,153,174,209)(H2,154,175,210)(H2,155,176,211)(H2,156,177,212)(H2,157,178,213)(H2,158,179,214)(H2,159,163,166)(H2,160,164,167)(H2,161,165,168)(H,182,203,215)(H,183,204,216)(H,184,205,217)(H,185,206,218)(H3,162,180,181,207)
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| Chemical Name |
1-[4-[[3-[[3-(2-amino-6-oxo-1H-purin-9-yl)-7-[[7-[[5-(4-amino-2-oxopyrimidin-1-yl)-3-[[3-[[3-(4-amino-2-oxopyrimidin-1-yl)-7-[[3-[[3-(4-amino-2-oxopyrimidin-1-yl)-7-[[3-[[3-(4-amino-2-oxopyrimidin-1-yl)-7-[[3-(4-amino-2-oxopyrimidin-1-yl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-3-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-[[[1-[[[5-(4-amino-2-oxopyrimidin-1-yl)-2-[[[3-(4-amino-2-oxopyrimidin-1-yl)-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-3-(6-aminopurin-9-yl)-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
H2O : 100 mg/mL (20.13 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 14.29 mg/mL (2.88 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 | 0.2042 mL | 1.0211 mL | 2.0421 mL | |
| 5 mM | 0.0408 mL | 0.2042 mL | 0.4084 mL | |
| 10 mM | 0.0204 mL | 0.1021 mL | 0.2042 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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