Macrocyclic Lipid 5|CAS|DC Chemicals

Cas No.:
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Cat. No.	Product name	Field of application
DC67721	Macrocyclic Lipid 5	Lipid 5 is an ionizable lipid based on a macrocyclic cyclam headgroup. Its structure incorporates a benzylmethyl carbonate (BMC) linker, which contains an aromatic benzene ring, and a saturated C18 hydrophobic tail. Lipid 5 was mixed with helper lipids at a fixed molar ratio and formulated into mRNA-loaded lipid nanoparticles (LNPs) using microfluidic technology. Characterization data show that these LNPs have a hydrodynamic diameter of approximately 50-80 nanometers and a polydispersity index (PDI) below 0.2, indicating a small particle size with a uniform distribution. Their zeta potential at physiological pH is near neutral (ranging from -3 to +3 mV). The mRNA encapsulation efficiency, as determined by the Ribogreen assay, exceeds 95%. Cryo-transmission electron microscopy images reveal that the LNPs exhibit a typical spherical bilayer structure. In in vitro experiments, Lipid 5 LNPs mediated a higher level of luciferase protein expression in HEK293FT cells compared to the benchmark lipid DLin-MC3-DMA. In Balb/c mice, intravenous injection of LNPs encapsulating luciferase mRNA resulted in in vivo imaging signals predominantly concentrated in the lungs. Quantitative analysis indicated that the signal intensity in the lungs was over 100 times greater than that in the liver, with more than 95% of the total signal distributed in the lungs. In Ai9 reporter gene mice, two intravenous injections of Lipid 5 LNPs encapsulating Cre mRNA led to quantitative analysis of lung tissue sections showing that approximately 30% of lung cells were positive for tdTomato signal.
DC67657	Lipid TS41	TS41 is a trisulfide-derived ionizable lipid engineered for lipid nanoparticles (LNPs) to deliver mRNA therapeutics against multidrug-resistant bacterial pneumonia. Its optimized formulation, TS41S LNP, combines TS41 with helper lipids (e.g., DOPE, cholesterol) at a precise ratio, achieving a hydrodynamic diameter of ~105 nm, low polydispersity, and high mRNA encapsulation efficiency (~84%). This design enables efficient pulmonary delivery via intratracheal administration, with luminescence signals in lungs 4.8-fold higher than clinical benchmarks like SM-102 LNPs, ensuring targeted expression in epithelial cells, macrophages, and neutrophils. Crucially, TS41 LNPs exhibit potent anti-inflammatory properties by scavenging reactive oxygen species (ROS), reducing neutrophil infiltration and proinflammatory cytokines (e.g., IL-6, TNF-α) in infected lungs. In preclinical models, TS41S LNP encoding PB9 peptibody mRNA eradicated pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, improved survival rates to 80%, and minimized tissue damage without systemic toxicity. Its ROS-scavenging capability synergizes with antibacterial effects, offering a promising, translatable platform for combating resistant infections while controlling inflammation. Future enhancements, such as codon optimization or inhalation delivery, could further broaden its therapeutic potential.
DC67538	XH-04	XH-04 (Lipid#4) is an ionizable lipid engineered for advanced mRNA delivery developed by JiaChen West Lake Biotech. Its core structure features a central benzene ring with asymmetric hydrophobic tails (C9-C10 chains) and pH-responsive tertiary amines that enable efficient mRNA encapsulation and endosomal escape. As detailed in CN113993839A, XH04 outperforms industry benchmarks (e.g., MC3 lipid), boosting protein expression by >10-fold in BHK cells. In PCT/CN2024/121624, JiaChen further demonstrated its utility in lung-targeted LNPs (tLNP/tLCNP). When combined with cationic lipids (e.g., DOTMA at 2:1 molar ratio), XH 04 redirects >80% of mRNA delivery to murine lungs—overcoming liver tropism—while maintaining low toxicity. The lipid’s benzenic core and optimized alkyl chain geometry (patent claims 1-9) are credited for enhanced endosomal disruption and mRNA release kinetics. JiaChen’s innovations position XH-04 as a cornerstone for next-generation mRNA therapeutics.
DC60855	4A3-SC7	4A3-SC7 is a proprietary, ionizable lipid component central to the SORT LNP platform developed for targeted organ delivery. It features a unique branched-tail structure designed to enhance mRNA encapsulation and endosomal escape. In the study, it served as the primary ionizable lipid in both Liver SORT LNPs and updated Lung SORT LNPs. For liver targeting, it was formulated at 15.04 mol% alongside helper lipids (DOPE: 23.04%, Cholesterol: 38.72%), PEG-lipid (DMG-PEG2000: 3.2%), and the liver-targeting lipid 4A3-Cit (20 mol%). This specific composition (Total lipid:RNA = 20:1 wt/wt) yielded LNPs with ~74 nm size, low PDI (0.17), and high encapsulation efficiency (87%) for large mRNAs like ABE editors (~5000 nt). Its branched-tail architecture was critical for stabilizing nanoparticles encapsulating large RNAs, overcoming a key limitation of previous formulations. 4A3-SC7-based Liver SORT LNPs enabled >40% base editing in hepatocytes in vivo, achieving durable correction of the disease-causing SERPINA1 mutation in PiZ mice and significantly reducing pathological protein aggregates. In the updated DualSORT system, 4A3-SC7 was also paired with DORI (instead of DOTAP) for improved lung targeting, demonstrating its versatility as a foundational ionizable lipid for multi-organ gene editing therapeutics.
DC67525	Hopewell Lipid 649	L649 is a next-generation, lung-targeting ionizable lipid specifically designed for systemic mRNA delivery developed by Hopewell. Belonging to the novel "N-series" lipid class, it features a unique structure with an amine-containing head group and hydrophobic tails incorporating amide bonds. This design enables L649 to form highly stable lipid nanoparticles (LNPs) that exhibit exceptional tropism for the lower respiratory tract (lungs, bronchi, trachea) following intravenous administration. It demonstrates superior efficiency in delivering therapeutic payloads (like mRNA) specifically to key lung cell types, including alveolar epithelial cells (AT1 and AT2) and bronchial cells, while minimizing off-target accumulation in organs like the liver. L649-based LNPs, particularly when formulated with helper lipids like POPE, combine high potency with significantly improved tolerability, allowing for effective dosing in vivo. This makes L649 a promising candidate for developing treatments for various lung diseases such as pulmonary fibrosis, COPD, lung cancer, and infectious diseases like COVID-19.
DC67449	Lipid TG4C	TG4C is an ionizable cationic lipid (pKa 6.71) optimized for mRNA delivery via lipid nanoparticles (LNPs). When formulated into LNPs carrying human EPO mRNA, it significantly elevates serum EPO levels in mice. Furthermore, aerosolized TG4C-based LNPs containing HGF mRNA demonstrate therapeutic potential in pulmonary emphysema models, showing reduced inflammatory cytokines (IL-1β, IL-6, TNF-α) in bronchoalveolar lavage fluid after elastase-induced lung injury.
DC60809	6Ac1-C12	6Ac1-C12 is an ester-core degradable ionizable cationic lipid designed for mRNA delivery, featuring a unique hexa-acrylate ester core ("6Ac1") conjugated with six N-methyldodecylamine chains ("C12") via solvent-free Michael addition. This branched architecture enables optimal mRNA encapsulation and confers exceptional stability, maintaining consistent ~100 nm particle size for over 30 days at 4°C—crucial for cold-chain storage. With a pKa ≈ 6.0, it facilitates pH-responsive endosomal escape through membrane fusion (80% FRET signal increase at pH 5.5) and efficient cytoplasmic mRNA release.Its composition allows precise organ targeting: in conventional four-component LNPs, 98% hepatic mRNA expression occurs post-IV administration, primarily in endothelial cells (60% transfection efficiency). Cholesterol removal enables lung-specific accumulation and translation via three-component formulations, overcoming historical hepatic off-targeting. The lipid shows negligible cytotoxicity in vitro (>85% cell viability) and no significant organ damage in vivo (ALT/AST/BUN/CREA levels comparable to PBS controls). Its degradable ester core hydrolyzes into smaller metabolites, enhancing biocompatibility. Modular compatibility with DOTAP/DDAB cationic lipids expands applicability for pulmonary or splenic targeting, establishing 6Ac1-C12 as a versatile platform for organ-selective mRNA therapeutics.
DC67292	IAJD34	IAJD-34 is a one-component ionizable amphiphilic Janus dendrimer specifically engineered for targeted mRNA delivery to the lung parenchyma, as described by Meshanni et al. in Nature Communications article "Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers" . This synthetic nanoparticle self-assembles with mRNA through simple mixing in acetate buffer, forming stable dendrimersomes approximately 93-97 nm in size with high encapsulation efficiency (>95%) and a positive zeta potential (~48 mV). Its defining feature, highlighted in the study, is exceptional lung tropism after intravenous injection, enabling significantly higher luciferase expression in murine lungs compared to other organs. As demonstrated by Meshanni et al., IAJD 34 effectively delivers therapeutic mRNA (e.g., TGF-β mRNA) to the lower lung, inducing transient protein production with minimal systemic toxicity at appropriate doses (e.g., 10 µg), offering a promising strategy for treating parenchymal lung diseases.
DC60793	LUMI6	The LUMI-6 lipid, autonomously designed via the LUMI-lab platform, is a brominated ionizable lipid optimized for mRNA delivery. Formulated at a molar ratio of 35:28:34.5:2 (LUMI-6:DOTAP:cholesterol:C14-PEG2000), LNPs exhibit uniform physicochemical properties, including a hydrodynamic diameter of ~80 nm, polydispersity index (PDI) <0.2, and robust mRNA encapsulation efficiency. In vitro, LUMI-6 LNPs demonstrated 1.8-fold higher transfection potency in human bronchial epithelial cells compared to its debrominated counterpart (LUMI-6D), with minimal cytotoxicity confirmed by CCK-8 assays. In vivo, pulmonary delivery of CRISPR-Cas9 mRNA via LUMI-6 LNPs achieved 20.3% gene editing efficiency in murine lung epithelial cells, surpassing SM-102 (Moderna’s clinical benchmark) and demonstrating preferential tropism for lung epithelium over endothelial cells—critical for inhaled therapies targeting cystic fibrosis and surfactant disorders. The brominated tail enhances endosomal escape through optimized protonation dynamics, though explicit pKa values remain unmeasured. Synthesized via high-throughput combinatorial chemistry and refined through AI-driven active learning, LUMI-6 combines scalable production with organ-selective delivery, positioning it as a transformative platform for pulmonary nucleic acid therapeutics.
DC60706	FO-35	FO35 is an artificial intelligence-guided designed ionizable lipid for RNA delivery to the muscle, lung and nose. FO-35 LNPs enable potent transfection throughout the whole ferret lung epithelium, from trachea to alveoli.