Drisapersen sodium targets dystrophin pre-mRNA at exon 51. By hybridizing to this region, it masks splice donor and acceptor sites, causing the spliceosome to bypass exon 51 during mRNA processing. This exon-skipping strategy is applicable to approximately 13% of Duchenne muscular dystrophy (DMD) patients who have amenable deletions in the dystrophin gene. The skipping event restores the translational reading frame.

In vitro, Drisapersen sodium is tested in patient-derived myoblast cell cultures carrying DMD gene deletions that disrupt the reading frame but are amenable to exon 51 skipping. Treatment with 10-20 uM Drisapersen for 48-72 h induces exon 51 skipping, as detected by RT-PCR and sequencing. Restored dystrophin protein expression is confirmed by Western blotting or immunofluorescence, typically achieving 10-30% of normal control levels depending on the specific mutation and treatment conditions.

In vivo studies were conducted in the mdx mouse model, which carries a nonsense mutation in exon 23 that is not amenable to exon 51 skipping. Therefore, efficacy was evaluated using humanized mouse models or non-human primates. A Phase 2 clinical trial in DMD patients showed that once‑weekly subcutaneous injection of Drisapersen (6 mg/kg) restored dystrophin expression in approximately 50% of treated patients as measured by muscle biopsy immunostaining after 12 weeks, with some patients achieving up to 15-20% of normal dystrophin levels.

The ability of Drisapersen to induce exon 51 skipping is assessed in a cell‑free splicing assay using nuclear extracts from HeLa cells together with a minigene construct containing human dystrophin exons 51-52 flanked by introns. The ASO (0.1-10 uM) is added, and RNA is isolated after a 2 h incubation. RT-PCR is performed using primers spanning the exon 51-52 junction. Skipping efficiency is calculated by densitometry of the shorter PCR product representing exon 51 deletion.

Primary human myoblasts from DMD patients with amenable deletions are differentiated into myotubes in 12‑well plates. Drisapersen is transfected using cationic lipids at concentrations of 5-25 uM. After 48 h, cells are harvested for RNA isolation and dystrophin mRNA analysis by nested RT-PCR. Dystrophin protein is detected by immunofluorescence using a C‑terminal antibody that recognizes the restored reading frame product. The percentage of dystrophin-positive myotubes is quantified by microscopy.

The in vivo efficacy of Drisapersen was evaluated in a Phase 2 open‑label clinical trial (NCT01153932). DMD patients with amenable deletions received once‑weekly subcutaneous injections of 6 mg/kg Drisapersen for 12 weeks. Muscle biopsies were taken from the tibialis anterior before the first dose and at week 12. The primary endpoint was the change in dystrophin-positive fibers from baseline as measured by immunohistochemistry. Secondary endpoints included the 6‑minute walk test (6MWT) for functional assessment.

Drisapersen sodium is administered subcutaneously. Its pharmacokinetic profile in patients shows dose-proportional exposure across 1-12 mg/kg. The terminal half‑life is approximately 2-4 weeks due to high protein binding and tissue distribution. Cmax is reached at 2-4 h post-dose. The plasma area under the curve (AUC) increases linearly with dose. Urinary excretion accounts for less than 5% of the administered dose, as it is mainly taken up by tissues, including skeletal muscle, where it exerts its pharmacodynamic effect.

In Phase 2 and Phase 3 clinical trials, Drisapersen was generally well-tolerated. The most common adverse events were injection site reactions, including erythema and pain, occurring in >90% of patients, as well as transient pyrexia, and subclinical proteinuria. More serious adverse events included thrombocytopenia (low platelet count) and renal toxicity. In 2015, the European Medicines Agency (EMA) issued a negative opinion on the marketing authorization application due to insufficient evidence of efficacy and safety concerns.

[1]. Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial. Neuromuscul Disord. 2014;24(1):16-24.

[2]. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014;13(10):987-996.

Drisapersen sodium was developed for Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. While it received orphan drug designation from both FDA and EMA, it failed to achieve regulatory approval. Following a phase 3 confirmatory trial (NCT02310906) that did not meet its primary endpoint, the sponsor discontinued development in 2016. However, the antisense oligonucleotide technology validated by Drisapersen paved the way for the FDA‑approved drug eteplirsen (Exondys 51), a phosphorodiamidate morpholino oligomer targeting the same exon. Drisapersen is now exclusively a research tool for studying exon‑skipping mechanisms in DMD.

C211H256N76NA19O119P19S19

7395.00

7392.415

1181666-20-5

121494117

Solid powder

27

172

136

463

19400

80

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FZJHBHYSGPESDI-FWLJYILUSA-A

InChI=1S/C211H275N76O119P19S19.19Na/c1-329-136-116(295)77(369-178(136)271-33-24-99(289)252-206(271)304)40-349-407(310,426)389-118-79(371-180(138(118)331-3)268-30-21-96(212)249-203(268)301)42-351-409(312,428)392-121-81(373-183(141(121)334-6)273-35-26-101(291)254-208(273)306)44-352-410(313,429)393-122-82(374-184(142(122)335-7)274-36-27-102(292)255-209(274)307)45-353-411(314,430)394-123-83(375-185(143(123)336-8)275-37-28-103(293)256-210(275)308)46-355-415(318,434)396-125-85(377-187(145(125)338-10)277-65-238-105-156(215)226-59-232-162(105)277)48-358-413(316,432)391-120-80(372-182(140(120)333-5)270-32-23-98(214)251-205(270)303)43-354-417(320,436)402-131-94(386-193(151(131)344-16)283-71-244-111-168(283)258-198(221)263-173(111)296)57-366-424(327,443)405-132-91(383-194(152(132)345-17)284-72-245-112-169(284)259-199(222)264-174(112)297)54-363-414(317,433)395-124-84(376-186(144(124)337-9)276-38-29-104(294)257-211(276)309)47-356-416(319,435)397-126-89(381-188(146(126)339-11)278-66-239-106-157(216)227-60-233-163(106)278)52-361-422(325,441)403-133-92(384-195(153(133)346-18)285-73-246-113-170(285)260-200(223)265-175(113)298)55-364-420(323,439)400-130-88(380-192(150(130)343-15)282-70-243-110-161(220)231-64-237-167(110)282)51-360-419(322,438)399-128-90(382-190(148(128)341-13)280-68-241-108-159(218)229-62-235-165(108)280)53-362-423(326,442)404-134-95(387-196(154(134)347-19)286-74-247-114-171(286)261-201(224)266-176(114)299)58-367-425(328,444)406-135-93(385-197(155(135)348-20)287-75-248-115-172(287)262-202(225)267-177(115)300)56-365-421(324,440)401-129-87(379-191(149(129)342-14)281-69-242-109-160(219)230-63-236-166(109)281)50-359-418(321,437)398-127-86(378-189(147(127)340-12)279-67-240-107-158(217)228-61-234-164(107)279)49-357-412(315,431)390-119-78(370-181(139(119)332-4)269-31-22-97(213)250-204(269)302)41-350-408(311,427)388-117-76(39-288)368-179(137(117)330-2)272-34-25-100(290)253-207(272)305;;;;;;;;;;;;;;;;;;;/h21-38,59-95,116-155,178-197,288,295H,39-58H2,1-20H3,(H,310,426)(H,311,427)(H,312,428)(H,313,429)(H,314,430)(H,315,431)(H,316,432)(H,317,433)(H,318,434)(H,319,435)(H,320,436)(H,321,437)(H,322,438)(H,323,439)(H,324,440)(H,325,441)(H,326,442)(H,327,443)(H,328,444)(H2,212,249,301)(H2,213,250,302)(H2,214,251,303)(H2,215,226,232)(H2,216,227,233)(H2,217,228,234)(H2,218,229,235)(H2,219,230,236)(H2,220,231,237)(H,252,289,304)(H,253,290,305)(H,254,291,306)(H,255,292,307)(H,256,293,308)(H,257,294,309)(H3,221,258,263,296)(H3,222,259,264,297)(H3,223,260,265,298)(H3,224,261,266,299)(H3,225,262,267,300);;;;;;;;;;;;;;;;;;;/q;19*+1/p-19/t76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,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-,151-,152-,153-,154-,155-,178-,179-,180-,181-,182-,183-,184-,185-,186-,187-,188-,189-,190-,191-,192-,193-,194-,195-,196-,197-,407?,408?,409?,410?,411?,412?,413?,414?,415?,416?,417?,418?,419?,420?,421?,422?,423?,424?,425?;;;;;;;;;;;;;;;;;;;/m1.................../s1

nonadecasodium;1-[(2R,3R,4R,5R)-5-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-2-(hydroxymethyl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-sulfidophosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(2,4-dioxopyrimidin-1-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(2,4-dioxopyrimidin-1-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(2,4-dioxopyrimidin-1-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(2,4-dioxopyrimidin-1-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)-4-methoxyoxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]-4-hydroxy-3-methoxyoxolan-2-yl]pyrimidine-2,4-dione

Kyndrisa sodium; GSK2402968A sodium; PRO051 sodium

2934.99.9001

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, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)