Hopewell Lipid 649|CAS|DC Chemicals

Cas No.:
Chemical Name:	Hopewell Lipid 649
SMILES:	CCCCCCCCCCC(C)SCCNC(=O)CCN(CCCN(C)CCCN(CCC(=O)NCCSC(C)CCCCCCCCCC)CCC(=O)NCCSC(C)CCCCCCCCCC)CCC(=O)NCCSC(C)CCCCCCCCCC
Formula:	C₇₅H₁₅₁O₄N₇S₄₁₃₄₃^.₃₂
M.Wt:	1343.32
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

MSDS

Cat. No.	Product name	Field of application
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.
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.
DC60663	Si5-N14	Si5-N14 is a lipid-based molecule engineered with siloxane groups, designed specifically for efficient mRNA delivery to the lungs. The incorporation of siloxane units boosts the cellular uptake of mRNA-loaded lipid nanoparticles (LNPs) and enhances their ability to escape from endosomes. These properties significantly increase the overall effectiveness of mRNA delivery, making Si5-N14 a promising tool for targeted therapeutic applications.
DC65682	RCB-4-8	RCB-4-8 is a biodegradable ionizable lipid nanoparticle (LNP) engineered for efficient pulmonary mRNA delivery and in vivo genome editing, as detailed in the primary research article "Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing" (Li et al., Nature Biotechnology 2023）. Synthesized from a combinatorial library of 720 biodegradable lipids via a three-component reaction system, RCB-4-8 features an alkyne-containing lipid tail and tertiary amine headgroup, optimized through high-throughput screening for superior lung-targeting capabilities. Its unique molecular design incorporates hydrolyzable ester and carbonate groups, enabling rapid biodegradation (<30% lung retention at 48 h vs. >90% for conventional lipids) while maintaining high transfection efficiency. When formulated with DOTAP instead of DOPE, RCB-4-8 LNPs achieved 100-fold higher luciferase mRNA expression in murine lungs compared to FDA-approved MC3 LNPs and mediated 95% GFP knockout in vitro. In Ai9 reporter mice, intratracheal delivery of RCB-4-8 loaded with Cre mRNA edited 53% of total lung cells after three doses, while codelivery with Cas9 mRNA/sgRNA yielded 7.2% tdTomato⁺ cells, rising to 17% when combined with AAV-sgRNAs. With an optimal particle size of 85.7 nm (PDI 0.11) and >87% mRNA encapsulation, RCB-4-8 supports repeat dosing and represents a transformative platform for inhalable gene therapies targeting congenital lung diseases like cystic fibrosis.
DC60489	LIPID 331	Lipid 331 is a biodegradable cyclic ionizable lipid. LNPs containing Lipid 331 result in robust transfection in the nasal and lung tissues of mice and efficient transfection of lung epithelial cells and lung-resident APCs. Lipid 331 is a promising candidate for mRNA vaccine delivery, offering the potential for further enhancing the potency of mRNA vaccines.