AX6​​ is an ionizable lipid in the ​​F32 LNP​​ formulation, engineered by ReNAgade/Orna Therapeutics for targeted mRNA delivery to T cells. AX-6's unique ​​bridged bicyclic/polycyclic core​​ with a ​​tertiary amine group​​ enables pH-dependent protonation and endosomal escape, while ​​C14-C18 hydrophobic tails​​ (optionally branched/fluorinated) enhance bilayer stability and mRNA encapsulation. Demonstrating ​​exceptional T-cell tropism​​, AX6 achieves high transfection efficiency in CD4+/CD8+ T cells (validated in NHP/humanized models) with minimal toxicity. Compared to clinical benchmarks (SM-102, ALC-0315), its rigid core offers superior ​​serum stability​​ and ​​immune-cell specificity​​, positioning it as an ideal candidate for ​​CAR-T/NK therapies​​ and ​​next-gen vaccines​​. The F32 LNP system's proven efficacy (e.g., in vivo B-cell depletion) underscores AX 6's transformative potential for ​​cell engineering​​ and ​​immunotherapies​​.

BHD-C2C2-PipZ, as an efficient ionizable cationic lipid, achieves high encapsulation efficiency and controllable release of mRNA through its unique chemical structure. In PEG-free 3P-LNPs, its electrostatic interaction with tripolyphosphate successfully replaces the steric stabilization effect of traditional PEG, offering a new strategy to circumvent PEG immunogenicity. Its hepatic distribution pattern further indicates that LNP design should take into account the heterogeneity of the organ microenvironment.

TE AA3-Dlin is an optimized lipid nanoparticle (LNP) carrier designed for mRNA-based cancer immunotherapy, enabling precise in vivo dendritic cell (DC) reprogramming to enhance antitumor immunity. TE AA3-Dlin LNP exhibits superior serum stability, maintaining consistent particle size and low turbidity under physiological conditions, while protecting mRNA from degradation, which is crucial for effective delivery. Functionally, TE AA3-Dlin preferentially targets splenic DCs by leveraging ApoE-enriched protein coronas, facilitating efficient cellular uptake and mRNA expression, as demonstrated by enhanced EGFP signals in DCs.This targeting promotes DC maturation, antigen presentation, and membrane-bound IL-15 expression, activating cytotoxic T lymphocytes (CTLs) for tumor rejection. In models like melanoma and colon carcinoma, it synergizes with checkpoint inhibitors, showing minimal toxicity and robust immunological memory.

Lipid A-12 is an ionizable cationic lipid from Capstan Therapeutics and a close analog of CICL-1 (L829). The structure was modified by the extension of the headgroup linker from a two-carbon (C2) to a three-carbon (C3) spacer compared to CICL-1 (L829).

4A3-LNSC8​ is a strategically designed thiourea-functionalized ionizable lipid that serves as the foundational core for a novel anion-coordination delivery platform. Its structure features a central 4A3 amine headgroup symmetrically extended with four hydrophobic tails, each incorporating a biodegradable ester linkage and a key thiourea-bridged linker. The inclusion of the thiourea group is the pivotal innovation, as it provides specific hydrogen-bonding sites capable of interacting with various halide anions (F⁻, Cl⁻, I⁻). When formulated into lipid nanoparticles (LNPs) without anion coordination, 4A3-LNSC8 itself exhibits a characteristic liver tropism, efficiently delivering mRNA to hepatocytes following systemic administration, with a measured surface pKa of approximately 5.54. However, its primary significance lies in its role as a versatile precursor. The strong anion-binding capability of its thiourea linkers allows for predictable modulation of the LNP's properties. Upon binding with anions like Cl⁻, the resulting complex (e.g., Cl-4A3-LNSC8) undergoes a significant pKa shift, which reprograms the LNP's in vivo fate, redirecting mRNA delivery from the liver to secondary lymphoid organs such as the spleen and lymph nodes. Thus, 4A3-LNSC8 is not merely an efficient ionizable lipid but a programmable scaffold that enables precise control over organ-targeting specificity through simple anion coordination, offering a powerful rational design strategy for advanced mRNA therapeutics.

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.

E12LA6B603（ILB3132，ILB-3132） is a novel ionizable amino lipid disclosed in patent WO2024198497A1, developed by MagicRNA, representing a highly efficient component for lipid nanoparticle (LNP) delivery systems.When formulated into LNPs, E12LA6B603 LNP achieves a remarkable 98.26% encapsulation efficiency for mRNA. It mediates superior in vitro transfection in dendritic cells (1.8E+05 intensity) and demonstrates best-in-class in vivo protein expression after intramuscular injection (2.2E+09 intensity). Most notably, in a B16-OVA melanoma model, therapeutic OVA-mRNA vaccines delivered by E12LA6B603 LNPs induced 100% complete tumor regression, highlighting its superior efficacy over benchmarks like DLin-MC3 and SM-102. Its biodegradable ester linkages and balanced structure make it a promising, potent candidate for next-generation mRNA vaccines and therapeutics.

CL15F 6-4 is a short-tail ionizable lipid from the piperidine-based CL15F series, characterized by its symmetric branched structure with a 6-carbon main chain and 4-carbon side chain. This specific tail length critically determines the lipid nanoparticle's (LNP) properties, resulting in larger particles with a high surface density of the phospholipid DSPC. This elevated DSPC density reduces interactions with serum proteins like ApoE, minimizing rapid liver clearance and shifting mRNA delivery preference towards the spleen. Consequently, CL15F 6-4 LNPs achieve efficient, endogenous spleen-targeted delivery, making them a highly promising candidate for enhancing vaccine efficacy by preferentially transfecting antigen-presenting cells without complex functionalization.

PyCB lipid (MeDZ) is a rationally designed zwitterionic ionizable lipid that serves as a core functional component in the novel three-component (ThrCo) lipid nanoparticle (LNP) platform. It is synthesized by covalently attaching a zwitterionic PyCB structure to the hydroxyl group of the clinically available ionizable lipid ALC-0315.Its key feature is its pH-responsive behavior. At physiological pH (~7.4), the PyCB headgroup exhibits zwitterionic properties, forming charge-assisted hydrogen bonds with water molecules (PyCB-H₂O complexes). This confers high hydrophilicity to the LNP surface, enhancing stability in aqueous environments and reducing nonspecific protein adsorption in the bloodstream. This zwitterionic surface effectively mimics and replaces PEGylated lipids, thereby avoiding PEG immunogenicity and the associated Accelerated Blood Clearance (ABC) effect upon repeated administrations.Crucially, in the acidic environment of endosomes (pH ~6.5), the PyCB group undergoes strong protonation, rapidly transforming into a cationic state (PyCB-H₃O⁺ complexes). This promotes efficient fusion with and disruption of the endosomal membrane, facilitating the escape and cytoplasmic release of encapsulated mRNA.By replacing both cholesterol and PEGylated lipids in traditional LNPs, PyCB lipid enables the redirection of LNP biodistribution from the liver to the spleen, achieving superior spleen-specific mRNA translation and enhancing antigen presentation for potent immune activation.

ARV-T1 is a novel ionizable lipid featuring a cholesterol moiety incorporated in its tail, designed to enhance mRNA delivery efficiency. With a pKa of 6.73, it exhibits optimal pH-dependent ionization for endosomal escape and mRNA release. Structurally, ARV-T1 contains a tertiary amine head group and ester-linked lipid tails, enabling rapid in vivo metabolism and improved biocompatibility.Compared to SM-102 (used in Moderna's vaccine), LNPs formulated with ARV-T1 demonstrate superior physicochemical properties: smaller particle size (~80 nm vs. 90 nm), lower polydispersity index (0.09 vs. 0.10), and higher absolute zeta potential (-10 mV vs. -5 mV). These characteristics correlate with >90% mRNA encapsulation efficiency and enhanced stability, maintaining performance for 12 weeks at -20°C.In vitro, ARV-T1 LNPs showed 7-fold higher protein expression than SM-102 LNPs. In vivo, they prolonged luciferase expression (>72 hours vs. <48 hours for SM-102) and induced 10-fold higher neutralizing antibodies against SARS-CoV-2 spike protein at low doses. The cholesterol tail promotes endosomal membrane fusion, while ester linkages facilitate metabolic clearance, yielding an excellent safety profile in toxicity studies. This combination of efficacy and safety positions ARV-T1 as a promising platform for mRNA vaccines and therapeutics.

Lipid S4 is an advanced ionizable lipid engineered for systemic mRNA delivery to the brain, leveraging SR-57227—a high-affinity 5-HT3 receptor ligand—as its core head group to enable targeted blood-brain barrier (BBB) penetration via receptor-mediated transcytosis, while incorporating amino linkers for pH-responsive ionization and biodegradable branched ester tails to facilitate efficient endosomal escape and intracellular mRNA release; optimized through orthogonal screening into OS4 LNP (formulated at S4/DOPE/Chol/DMG-PEG2k = 40:40:60:0.75 molar ratio), it demonstrated a 13.3-fold increase in brain mRNA expression compared to FDA-approved MC3 LNPs, and further conjugation with the Tat cell-penetrating peptide yielded OS4T LNP, boosting delivery efficiency by 12.7-fold over OS4 alone and enabling broad mRNA expression across neurons, astrocytes, microglia, and endothelial cells; validated in orthotopic glioblastoma models, OS4T delivered engineered IL-12 mRNA, suppressing tumor growth and extending median survival to 37 days (vs. 17 days for controls) with minimal systemic toxicity, positioning S4-based LNPs as a robust, translatable platform for CNS-targeted therapeutics.

A28-C6B2 is a biodegradable ionizable lipid specifically engineered for spleen-targeted delivery. Through its unique branched structure, it bypasses hepatic uptake to achieve highly efficient transfection of F4/80+ macrophages and CD11c+ dendritic cells within the spleen. This lipid remains neutral in the bloodstream to minimize non-specific interactions, while undergoing protonation in the acidic environment of the endosome to facilitate nucleic acid release, thereby significantly enhancing the potency of mRNA vaccines and immunotherapies.

MMG-11 quarterhydrate is a potent and selective human TLR2 antagonist with low cytotoxicity. MMG-11 quarterhydrate inhibits both TLR2/1 and TLR2/6 signaling with IC50s of 1.7?μM for Pam3CSK4-induced hTLR2/1 and 5.7?μM for Pam2CSK4-induced hTLR2/6 responses.

MMG-11 is a potent and selective dual inhibitor of TLR2/1 and TLR2/6 signaling with low cytotoxicity.

MMG-1, a monomycoloyl glycerol, is a C-type lectin receptor agonist. MMG-1, a lipid membrane stabilizer, is an immunopotentiator in liposomes. MMG-1 can be used to prepare lipid nanoparticles for drug delivery.

Triantennary GalNAc ligand is known to bind Asialo Glycoprotein Receptor (ASGPR). The ligand is functionalized with dibenzocyclooctyne for click chemistry.

Triantennary GalNAc ligand is known to bind Asialo Glycoprotein Receptor (ASGPR). The ligand is functionalized with dibenzocyclooctyne for click chemistry

(β-D-GalNAc-sp)3-NHC(O)-(CH2)2-NHC(O)-PEG3-(CH2)2-N3 Tris-β-D-GalNAc ligands bind with asialoglycoprotein receptors (ASGPR) that are highly expressed on hepatocytes resulting in rapid endocytosis of the ligand along with conjugated payloads

An amine-reactive asialo glycoprotein receptor (ASGPR) ligand.

VL422 is a novel ionizable cationic lipid, as a high-performance "molecular engine" for next-generation Lipid Nanoparticles (LNPs), specifically engineered for the precise delivery of CRISPR base editors and mRNA. Its sophisticated chemical architecture is designed to remain neutral in systemic circulation for enhanced safety, while rapidly protonating within the acidic cellular environment to trigger efficient endosomal escape and cargo release. Validated by groundbreaking research in liver-targeted gene silencing, VL422 has become a critical benchmark molecule for developing permanent, transformative therapies for cardiovascular and metabolic diseases.

H5T5 is a leading ionizable lipid nanoparticle (LNP) formulation optimized for in vivomRNA delivery, featuring a pKa of 6.51, a size of ~154 nm, and a narrow polydispersity index (PDI) of 0.05. It demonstrated superior in vitromRNA transfection efficiency in primary immune cells, such as bone marrow-derived macrophages. Following intravenous administration, H5T5 exhibits precise organotropism, predominantly targeting the spleen and bone marrow, where it effectively delivers mRNA to a broad spectrum of immune cells, including macrophages, dendritic cells, T cells, B cells, and NK cells. This capability enables its core application: the in vivogeneration of "pan-CAR" immune cells. When loaded with anti-HER2 CAR mRNA, the H5T5-based therapy achieved potent tumor regression and prolonged survival in multiple solid tumor models. Preliminary safety assessments indicated a manageable cytokine profile and no significant organ toxicity, positioning it as a promising platform for in vivocell engineering.

Sail Lipid 2308​ is a novel ionizable lipid targeting to spleen developed by Sai Biomedicine.As described on US20250205167A1, Lipid 2308 was designed with a ​​piperidine core​​ (6-membered ring) and asymmetric C17/C11 chains, this lipid achieves unprecedented ​​spleen-specificity​​. It demonstrates dominant spleen accumulation (Spleen RLU: ​​7.8E+06​​, 91.8% of total signal) with a record ​​spleen-to-liver ratio of 112.7​​ (9× higher than 2231). Despite lower protein expression (hEPO: 11,000 ng/mL), near-zero liver uptake (Liver RLU: 66,000) makes Lipid 2308 unparalleled for vaccine/immunotherapy applications targeting splenic immune cells.

CICL-242​ is a constrained ionizable cationic lipid highlighted in patent US 20250127728A1 developed by Capstan as a promising candidate for advanced therapeutic delivery, particularly in stem cell and gene editing applications. Its structure features a rigid amine headgroup similar to CICL-207, which likely facilitates efficient endosomal escape and reduces non-specific uptake, enhancing targeted nucleic acid delivery. Although detailed performance data is not fully disclosed in the patent, CICL-242 is explicitly synthesized and included in gene editing experimental systems (e.g., CRISPR-Cas9 workflows), suggesting its potential for high-efficiency transfection in hard-to-transfect cells​ like hematopoietic stem cells (CD34⁺). This makes it a strong candidate for ex vivo cell engineering and regenerative medicine, where precision and low off-target effects are critical. While further validation is needed to quantify its efficacy and safety profile, CICL-242 represents a strategic innovation in the lipid library for next-generation genetic therapies.

CHCha-10 is an amino acid-derived ionizable lipid engineered for pulmonary gene therapy. Its optimal surface charge (-0.126 mV) enables efficient mucus penetration, while a pKa of ~7.0 facilitates endosomal escape. Its unique conical structure promotes membrane fusion and mRNA release. In animal models, CHCha-10-based LNPs achieved highly efficient and specific editing of lung epithelial cells, particularly stem-like basal cells (~44%), with effects persisting through tissue renewal. It also demonstrated excellent efficacy and safety in ferrets, a model closely mimicking human lung physiology.

ISM5939 is an orally active and selective ENPP1 inhibitor with an IC50 of 0.63 nM for 2,3-cGAMP degradation and 9.28 nM for ATP hydrolysis. ISM5939 has antitumor activity.

BioE-1197 is a novel Pask inhibitor. BioE-1197 is a compound that enhances T cell function. Functionally, treatment with BIOE-1197 significantly boosts the ability of effector T cells (such as CD8+, Th1, and Th2 cells) to produce lineage-specific cytokines upon restimulation. BIOE-1197 is considered a novel agent with potential applications in tumor immunotherapy and enhancing vaccine efficacy.

Emupertinib (example 37) is a potent EGFR inhibitor with IC50 values of <0.3 nM, 0.52 nM, 0.5 nM, 0.69 nM and 0.92 nM for EGFR (d746-750/T790M/C779S), EGFR (L858R/T790M/C797S), EGFR (d746-750/C797S), EGFR (L858R/C797S), and EGFR (wild-type), respectively.

KVS0001 is a specific and bioavailable small molecule inhibitor of SMG1 kinase, disrupts nonsense mediated decay (NMD).

AURKB PROTAC MS44 is a potent, selective, first-in-class Aurora B kinase (AURKB) PROTAC degrader with DC50 of 103 nM in HPAF-11 cells, Dmax of 89%.