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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
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Structure of 96-54-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
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Batch number can be found on the product's label following the word 'Batch'.
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Gong, Ningqiang ; Kim, Dongyoon ; Alameh, Mohamad-Gabriel ; El-Mayta, Rakan ; Han, Emily L ; Dwivedi, Garima , et al.
Abstract: The immunogenicity of lipid nanoparticles (LNPs) used for the delivery of nucleoside-modifed messenger RNA limits the levels and durability of expression of the encoded protein. Here, by leveraging the Mannich reaction for ionizable lipid synthesis, and via the in vitro and in vivo screening of six combinatorial libraries of synthesized lipids, we report the identifcation of an antioxidant ionizable lipid, C-a16, exhibiting reduced immunogenicity. When incorporated into LNPs for mRNA delivery, C-a16 mitigated the generation of intracellular reactive oxygen species, thereby extending the duration of protein expression. In mice, and compared with commercial LNPs, LNPs incorporating C-a16 and co-delivering Cas9 mRNA and guide RNA for the editing of the transthyretin gene led to 2.8-fold higher editing efciency; LNPs with C-a16 delivering fbroblast growth factor 21 mRNA increased the expression of the protein 3.6-fold; and when delivering mRNA encoding a tumour neoantigen or the spike protein of SARS-CoV-2, LNPs with C-a16 induced stronger antigen-specifc immune responses. Our fndings support the further testing of C-a16 as a promising ionizable lipid for mRNA delivery in therapeutic applications.
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CAS No. : | 96-54-8 |
Formula : | C5H7N |
M.W : | 81.12 |
SMILES Code : | CN1C=CC=C1 |
MDL No. : | MFCD00005345 |
InChI Key : | OXHNLMTVIGZXSG-UHFFFAOYSA-N |
Pubchem ID : | 7304 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H315-H319-H335 |
Precautionary Statements: | P210-P261-P305+P351+P338 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅱ |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 25.69 |
TPSA ? Topological Polar Surface Area: Calculated from |
4.93 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.72 |
Solubility | 1.54 mg/ml ; 0.019 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.91 |
Solubility | 9.97 mg/ml ; 0.123 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.05 |
Solubility | 7.2 mg/ml ; 0.0887 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.94 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With trimethylsilyl trifluoromethanesulfonate; In 1,2-dichloro-ethane; at 25℃; for 0.5h; | General procedure: The mixture of asodium arylsulfinate (0.2 mmol, 1.0 equiv), a pyrrole/thiophene (0.3 mmol, 1.5equiv) and TMSOTf (0.4 mmol, 2.0 equiv) in (ClCH2)2 (1.0 mL) was stirred at25 C for 0.5 h, then water (5 mL) and dichloromethane (10 mL) were added.The two layers were separated, and the aqueous phase was extracted withdichloromethane (3 × 10 mL). The combined organic extracts were washed bybrine, dried over anhydrous Na2SO4, filtered, and concentrated. The residuewas purified by flash chromatography on silica gel (ethyl acetate : petroleumether = 1:1) to afford the desired sulfoxides 4. |
A337205 [43036-06-2]
3-(1H-Pyrrol-1-yl)propanenitrile
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