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DLin-M-C4-DMA

Cat No.:V73439 Purity: ≥98%
DLin-M-C4-DMA (Compound MC4) is a cationic lipid.
DLin-M-C4-DMA
DLin-M-C4-DMA Chemical Structure CAS No.: 1226909-66-5
Product category: Liposome
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
50mg
Other Sizes
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Product Description
DLin-M-C4-DMA (Compound MC4) is a cationic lipid. DLin-M-C4-DMA can be used for nucleic acid delivery.
DLin-M-C4-DMA (DLin-MC4-DMA) (CAS#: 1226909-66-5) is a synthetic ionizable cationic lipid belonging to the DLin-DMA family. It features a dimethylamino headgroup and dual linoleoyl tails, with a molecular weight of 656.1 g/mol. DLin-M-C4-DMA is an ionizable lipid with a pKa of 6.93 and an advanced dimethylaminobutyl headgroup that provides enhanced buffering capacity. This lipid is designed for the efficient encapsulation and delivery of nucleic acids, such as siRNA and mRNA, as part of lipid nanoparticle (LNP) formulations.
Biological Activity I Assay Protocols (From Reference)
Targets
DLin-M-C4-DMA does not have a specific biological receptor target. As an ionizable cationic lipid, its primary function is to facilitate the encapsulation and intracellular delivery of nucleic acids. At physiological pH, the lipid is largely neutral, but it becomes positively charged in the acidic environment of the endosome. This property enables endosomal escape, allowing the nucleic acid cargo to be released into the cytoplasm. Its pKa of 6.93 is optimized for this function.
ln Vitro
In vitro, DLin-M-C4-DMA is used to formulate lipid nanoparticles (LNPs) for nucleic acid delivery. LNPs containing DLin-M-C4-DMA can encapsulate siRNA or mRNA and deliver them to cells in culture. The ionizable nature of the lipid facilitates endosomal escape, which is a critical step for the effective delivery of nucleic acid therapeutics. The compound's ability to complex with and protect nucleic acids is assessed in these in vitro studies.
ln Vivo
In vivo, DLin-M-C4-DMA-containing LNPs have been shown to be effective for nucleic acid delivery. Lipid nanoparticles containing DLin-MC4-DMA and encapsulating siRNA for the gene encoding mouse coagulation factor VII (F7) reduce its gene expression levels in mice. This demonstrates the compound's utility in achieving functional delivery of siRNA to target tissues in vivo.
Enzyme Assay
In vitro assays for DLin-M-C4-DMA typically involve the formulation of lipid nanoparticles (LNPs) and the assessment of their nucleic acid encapsulation efficiency, size, and zeta potential. The pKa of the lipid is determined using a TNS (2-(p-toluidino)naphthalene-6-sulfonic acid) binding assay. The ability of the LNPs to deliver functional nucleic acids is assessed in cell culture by measuring the knockdown of a target gene (for siRNA) or the expression of a reporter protein (for mRNA).
Cell Assay
Cellular assays for DLin-M-C4-DMA typically involve treating cells with LNPs formulated with the lipid and encapsulating a nucleic acid cargo. The efficiency of delivery is measured by assessing the functional outcome, such as gene knockdown (for siRNA) or protein expression (for mRNA). Cytotoxicity is also evaluated to ensure the formulation is well-tolerated by cells.
Animal Protocol
In vivo animal studies for DLin-M-C4-DMA typically involve the intravenous administration of LNP formulations to mice. The efficacy of the formulation is assessed by measuring the reduction in target gene expression (e.g., Factor VII) in the liver or by evaluating the therapeutic effect in a disease model. Pharmacokinetics and biodistribution of the LNPs may also be evaluated.
ADME/Pharmacokinetics
DLin-M-C4-DMA is an ionizable cationic lipid with a pKa of 6.93. It has a molecular weight of 656.1 g/mol and is supplied as a liquid. It is soluble in chloroform and methanol and is typically stored at -20°C. Detailed pharmacokinetic parameters are not available in the public domain but are characteristic of ionizable lipids used in LNP formulations.
Toxicity/Toxicokinetics
There is no specific toxicity data reported for DLin-M-C4-DMA in the available literature. As a research chemical, it should be handled with standard safety precautions. The compound is not approved for human therapeutic use. Toxicity studies would be required if the compound were to be used in clinical formulations.
References

[1]. Lipids and lipid nanoparticle formulations for delivery of nucleic acids. Patent US10166298. 2019-01-01.

Additional Infomation
DLin-M-C4-DMA (DLin-MC4-DMA) is a synthetic ionizable cationic lipid used for nucleic acid delivery. It has a pKa of 6.93 and a molecular weight of 656.1 g/mol. LNPs containing this lipid have been shown to reduce gene expression in mice, demonstrating their in vivo efficacy for siRNA delivery.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Exact Mass
655.627
CAS #
1226909-66-5
PubChem CID
58559556
Appearance
Colorless to light yellow liquid
Hydrogen Bond Donor Count
0
Rotatable Bond Count
37
Heavy Atom Count
47
Complexity
702
Defined Atom Stereocenter Count
0
SMILES
CCCCC/C=C\\C/C=C\\CCCCCCCCC(OC(=O)CCCCN(C)C)CCCCCCCC/C=C\\C/C=C\\CCCCC
InChi Key
QNUBVWOFCJNYJO-KWXKLSQISA-N
InChi Code
InChI=1S/C44H81NO2/c1-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-35-39-43(47-44(46)41-37-38-42-45(3)4)40-36-34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-2/h13-16,19-22,43H,5-12,17-18,23-42H2,1-4H3/b15-13-,16-14-,21-19-,22-20-
Chemical Name
[(6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl] 5-(dimethylamino)pentanoate
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

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~100 mg/mL (~152.4 mM; with ultrasonication)
Solubility (In Vivo)
Solubility in Formulation 1: 2.5 mg/mL (3.81 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Suspended solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
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.

Solubility in Formulation 2: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well.

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

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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