| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Complement component 5 (C5)
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|---|---|
| ln Vitro |
With an IC50 value of 474.5 pM, zilucoplan (RA101495; 1-1000 nM; 30 min) inhibits the increase in C5a plasma levels in human whole blood caused by lipopolysaccharides. When zilucoplan is used at a concentration of 1 nM, C5a plasma levels are reduced by 65.7% [2]. By preventing C5 from being broken down by C5 convertase into C5a and C5b and attaching to preformed C5b to sterically block interaction with C6, zilucoplan binds to complement component 5 (C5) and prevents the downstream assembly of the membrane attack complex (MAC; C5b-9)[1].
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| ln Vivo |
In C5-deficient mice treated with human complement, zilucoplan (RA101495; 10 mg/kg; SC; daily, for 6 d) inhibits the development of immune-mediated necrotizing myopathy (IMNM)[1]. In C57BL/6 mice, zilucoplan (10 mg/kg; SC; daily, for 6 d) shows protective effects on the prevention of myopathy[1].
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| Animal Protocol |
Methods: purified immunoglobulin G (IgG) from an anti-HMGCR+ IMNM patient was co-injected intraperitoneally with human complement in C57BL/6, C5-deficient B10 (C5def) and Rag2 deficient (Rag2-/-) mice. Zilucoplan was administered subcutaneously in a preventive or interventional paradigm, either injected daily throughout the duration of the experiment in C57BL/6 and C5def mice or 8 days after disease induction in Rag2-/- mice. [1]
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| References | |
| Additional Infomation |
Introduction: Immune-mediated necrotizing myopathy (IMNM) is associated with pathogenic anti-signal recognition granule (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies, at least in part, through activation of the classical complement pathway. We evaluated the efficacy of the investigational drug zilucoplan (a macrocyclic peptide inhibitor of complement component 5 (C5)) using a humanized IMNM mouse model. Methods: Purified immunoglobulin G (IgG) from anti-HMGCR-positive IMNM patients was co-intraperitoneally injected with human complement into C57BL/6, C5-deficient B10 (C5def), and Rag2-deficient (Rag2-/-) mice. Zilucoplan was administered subcutaneously daily in C57BL/6 and C5def mice as a prophylactic or interventional regimen, and on day 8 post-disease in Rag2-/- mice. Results: Prophylactic administration of ziroblan prevented muscle strength decline in C5-deficient mice (anti-HMGCR+ group vs. anti-HMGCR++ ziroblan group: p = 0.0289; control group vs. anti-HMGCR++ ziroblan group: p = 0.4634) and wild-type C57BL/6 mice (anti-HMGCR+ group vs. anti-HMGCR++ ziroblan group: p = 0.0002; control group vs. anti-HMGCR++ ziroblan group: p = 0.0939), while also reducing C5b-9 deposition on muscle fibers and the number of regenerated muscle fibers. Following disease induction, ziroblan intervention in Rag2-/- mice reduced complement deposition and the number of regenerated muscle fibers in muscle, but to a lesser extent. In the latter case, C5 inhibitors did not significantly improve muscle strength. Conclusion: In the humanized IMNM mouse model, early administration of zirupram can prevent the occurrence of myopathy at both the clinical and histological levels. [1]
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| Molecular Formula |
C128H190N24O33
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|---|---|
| Molecular Weight |
2593.02
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| Exact Mass |
2591.39271
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| Related CAS # |
1841136-73-9
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| PubChem CID |
171042923
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| Appearance |
Typically exists as solids at room temperature
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| LogP |
8
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| Hydrogen Bond Donor Count |
28
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| Hydrogen Bond Acceptor Count |
35
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| Rotatable Bond Count |
76
|
| Heavy Atom Count |
185
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| Complexity |
5600
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| Defined Atom Stereocenter Count |
16
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| SMILES |
CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCCC(=O)NCCCC[C@@H](C(=O)O)NC(=O)[C@H](C1CCCCC1)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC3=CC=C(C=C3)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC4=CNC5=C4C=CC=N5)NC(=O)[C@H](CC6=CC=C(C=C6)O)NC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(=O)O)N(C)C(=O)[C@@H]7CC(=O)NCCCC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N7)CC8=CC=CC=C8)CCCNC(=N)N)CCC(=O)O)C(C)C)NC(=O)C)C(=O)O
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| InChi Key |
VCUCVVRJWKIPFX-MYCQSYGYSA-N
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| InChi Code |
InChI=1S/C128H190N24O33/c1-9-10-11-12-13-14-15-16-17-18-19-20-27-44-102(158)138-92(126(182)183)53-56-100(156)133-64-67-185-69-68-184-66-59-101(157)131-60-31-29-41-91(125(180)181)142-121(176)108(82-37-25-22-26-38-82)149-118(173)98-43-34-65-152(98)124(179)96(72-81-47-51-85(155)52-48-81)146-113(168)89(54-57-104(160)161)140-117(172)95(73-83-76-136-110-86(83)39-32-62-134-110)144-115(170)94(71-80-45-49-84(154)50-46-80)145-122(177)109(128(5,6)7)150-119(174)99(75-106(164)165)151(8)123(178)97-74-103(159)132-61-30-28-40-87(137-78(4)153)114(169)148-107(77(2)3)120(175)141-90(55-58-105(162)163)112(167)139-88(42-33-63-135-127(129)130)111(166)143-93(116(171)147-97)70-79-35-23-21-24-36-79/h21,23-24,32,35-36,39,45-52,62,76-77,82,87-99,107-109,154-155H,9-20,22,25-31,33-34,37-38,40-44,53-61,63-75H2,1-8H3,(H,131,157)(H,132,159)(H,133,156)(H,134,136)(H,137,153)(H,138,158)(H,139,167)(H,140,172)(H,141,175)(H,142,176)(H,143,166)(H,144,170)(H,145,177)(H,146,168)(H,147,171)(H,148,169)(H,149,173)(H,150,174)(H,160,161)(H,162,163)(H,164,165)(H,180,181)(H,182,183)(H4,129,130,135)/t87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,107-,108-,109+/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,14S,22S)-22-acetamido-11-benzyl-8-(3-carbamimidamidopropyl)-5-(2-carboxyethyl)-3,6,9,12,16,23-hexaoxo-2-propan-2-yl-1,4,7,10,13,17-hexazacyclotricosane-14-carbonyl]-methylamino]-3-carboxypropanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-2-cyclohexylacetyl]amino]-6-[3-[2-[2-[[(4S)-4-carboxy-4-(hexadecanoylamino)butanoyl]amino]ethoxy]ethoxy]propanoylamino]hexanoic acid
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| Synonyms |
Zilucoplan (PEG2); Zilucoplan PEG2
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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 |
| 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) |
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
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|---|---|
| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3857 mL | 1.9283 mL | 3.8565 mL | |
| 5 mM | 0.0771 mL | 0.3857 mL | 0.7713 mL | |
| 10 mM | 0.0386 mL | 0.1928 mL | 0.3857 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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