HCQ Lipid 4（HCQ-4）|CAS|DC Chemicals

Cas No.:
Chemical Name:	HCQ Lipid 4（HCQ-4）
Synonyms:	HCQ-Lipid-4，Lipid 4
SMILES:	CCCCCCCCCCCCCCN(CCCCCCCCCCCCCC)C(=O)CCC(=O)OCCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1
Formula:	C₅₀H₈₇O₃ClN₄
M.Wt:	827.72
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
DC67989	Cl-4A3-LNSC8	Cl-4A3-LNSC8 represents a novel class of thiourea-functionalized ionizable lipids engineered for selective organ-targeted mRNA delivery. Its core innovation lies in an anion-coordination strategy, where the parent lipid, 4A3-LNSC8, binds chloride ions (Cl⁻) via hydrogen-bonding interactions with its thiourea groups. This binding event is not merely structural but functionally critical, as it induces a significant shift in the surface pKa of the resulting lipid nanoparticles (LNPs) from approximately 5.54 to 8.79. This pKa modulation is the key mechanism that redirects the organotropism of the LNPs upon systemic administration. While the unmodified 4A3-LNSC8 LNPs preferentially deliver mRNA to the liver, Cl-4A3-LNSC8 LNPs effectivelyreprogram this tropism, enabling highly efficient mRNA delivery to secondary lymphoid organs (SLOs), particularly the spleen and lymph nodes. This platform demonstrates remarkable efficacy, achieving up to 65.7% gene editing efficiency in splenic macrophages in vivo, significantly outperforming benchmark delivery systems. Furthermore, by leveraging the coordination with different halides, such as iodine for computed tomography (CT) contrast, the system can be adapted for dual-modal theranostic applications, enabling simultaneous lymphatic metastasis imaging and therapeutic mRNA delivery.
DC67544	HCQ Lipid 4（HCQ-4）	HCQ-4 is a rationally engineered ionizable lipid derived from hydroxychloroquine (HCQ), featuring a ditetradecylamine-derived twin-C14 saturated hydrocarbon tail linked to the HCQ headgroup via a succinic acid spacer. Synthesized through a three-step route involving HCQ deprotonation, ditetradecylamine carboxylation, and EDC/DMAP-mediated amidation, this lipid forms the core of optimized lipid nanoparticles (LNPs) at a molar ratio of 60:10:40:0.5 (HCQ-4:DOPE:cholesterol:DMG PEG₂₀₀₀). The structure enables dual functionality: (1) Spleen-selective mRNA delivery (2.3-fold higher splenic vs. hepatic transfection) via 80-100 nm particle size, near-neutral charge (-3 mV), and low PEG density, facilitating immune cell uptake; (2) Tumor microenvironment modulation through HCQ-mediated repolarization of M2 macrophages to antitumor M1 phenotype (iNOS⁺ cells ↑2.5-fold, CD206⁺ cells ↓60%). This bifunctional design synergistically enhances mRNA cancer vaccine efficacy, demonstrating superior prophylactic/therapeutic antitumor activity and antimetastatic effects compared to clinical benchmarks like MC-3 LNP.
DC67450	A28-C6B2	A28-C6B2 is an ionizable lipid (pKa 6.43) designed for mRNA encapsulation in lipid nanoparticles (LNPs). Following intravenous injection in mice, these LNPs exhibit spleen-selective accumulation, particularly localizing in F4/80+ macrophages and CD11c+ dendritic cells, with moderate uptake by T lymphocytes.