AA76-lipid is a dipeptide-modified ionizable lipid, engineered with an arginine-histidine motif, that constitutes the core of the pancreatic-targeted AH-LNP delivery platform. Its chemical architecture, characterized by an externally positioned and C-terminally modified arginine residue, was identified through systematic screening as the optimal structure for function. Upon intraperitoneal administration, AH-LNPs formulated with this lipid interact with proteins in the peritoneal fluid, undergoing dynamic assembly into significantly larger complexes. This substantial increase in size (from ~100 nm to over 360 nm) exploits a physical targeting principle termed the Capsule-filter-mediated pancreatic targeting (CAMP) mechanism. Large particles are selectively filtered out by the dense capsules of other abdominal organs, leading to preferential enrichment in the capsule-deficient pancreas. Concurrently, the arginine-histidine motif directs the formation of a distinct protein corona enriched with apolipoproteins (e.g., APOE, APOB-100), which mimics very-low-density lipoprotein (VLDL). This corona enables efficient cellular internalization primarily into pancreatic stromal cells via VLDL receptor (VLDLR)-mediated endocytosis, known as the VMP pathway. The synergistic integration of the physical CAMP targeting and the biological VMP uptake mechanisms empowers AA76-lipid-based AH-LNPs to achieve highly specific, potent, and sustained mRNA delivery and gene editing within the pancreas across multiple species, demonstrating exceptional therapeutic efficacy in models of both autoimmune pancreatitis and pancreatic cancer.

Lipid 2298 is a novel ionizable lipid developed by Sai Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 3.448​ and a very high total expression level of 2.4E+07. Lipid 2298 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen.

Lipid 2310 is a novel ionizable lipid developed by Sail Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 5.58 and a very high total expression level of 1.3E+07. Lipid 2310 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen.

Lipid 2306 is a novel ionizable lipid developed by Sail Biomedicine demonstrates excellent performance with a spleen-to-liver ratio of 3.68 and a very high total expression level of 2.5E+07. Lipid 2306 offers a strong balance of efficient systemic protein production and clear preferential delivery to the spleen.

Lipid OC7, as described in the patent WO2022207938A1, is a novel ionizable lipid that serves as the core functional component of the saNppa-LNP delivery system. Its key innovation lies in its unique biodegradable structure featuring an internal ester bond. Under typical physiological conditions, this bond hydrolyzes, triggering a charge shift from a cationic form that complexes nucleic acids to a zwitterionic form that releases them. This property is central to its role in enabling long-acting self-amplifying RNA (saRNA) therapies. Specifically, OC7 facilitates immune stealth by mitigating early interferon responses, supports sustained and efficient intracellular replication of saRNA even at low doses, and enables therapeutic protein expression that persists for over 28 days from a single administration. This combination of efficient delivery, controlled release, and extended duration of action makes OC7-based LNPs a promising platform for long-term treatments, such as for myocardial infarction, as demonstrated in the referenced research.

​​Lipid 10a-26​​ is an ionizable lipid developed by Orna Therapeutics for lipid nanoparticle (LNP) formulations. Lipid 10a-26 is a key ionizable lipid in the LNP-6 formulation. Through structural modification, it exhibits reduced binding to ApoE proteins and lowered liver affinity compared to traditional ionizable lipids. Instead, Lipid 10a-26 demonstrates strong splenic tropism—in non-human primate studies, it effectively delivers payloads to the spleen and immune cells in peripheral blood, such as T cells, NK cells, and macrophages, enabling the possibility of "in vivo CAR-T" therapy. Its pKa is tuned to approximately 6.0–6.5, allowing rapid protonation in the acidic endosomal environment, which promotes endosomal membrane disruption and efficient cytosolic release of circular RNA.

98N12-5 is an ionizable cationic lipid. It has been used in combination with other lipids in the generation of lipid nanoparticles (LNPs). LNPs containing 98N12-5 and encapsulating proprotein convertase subtilisin kexin type 9 (PCSK9) siRNA selectively accumulate in the liver and reduce total serum cholesterol levels in mice and rats and serum LDL levels in cynomolgus monkeys.

246C10 is a synthesized ionizable lipid. 246C10 can be formulated into lipid nanoparticles (LNPs) with dioleoylphosphatidylethanolamine (DOPE), cholesterol, and C16-PEG2000 ceramide (PEG-lipid) as well as mRNA. The lipid nanoparticle formulations can be used for mRNA delivery. To obtain iLNPs that could specifically target liver sinusoidal endothelial cells (LSECs), six different ionizable lipids (241C10 to 246C10) were synthesized by an epoxide ring-opening reaction with piperazine- or piperidine-containing amines. Biodistribution and gene regulation of various iLNPs were assessed in vivo, and the results showed that the 246C10 iLNPs (containing piperazine amine) had the highest luciferase expression in the liver. When further analyzing the 246C10 iLNPs transfection efficiency in different types of liver cells, it was found that tdTomato fluorescence was mainly concentrated in hepatocytes, not in LSECs. Figure 6f shows that 80% of hepatocytes are fluorescent, 40% of LSECs are fluorescent, and 20% of Kupffer cells are fluorescent. Due to the mannose receptor on LSECs, mannose-PEG lipid was introduced into 246C10 iLNPs to alter the distribution of iLNPs in different liver cells. As shown in Figure 6g, tdTomato fluorescence distribution was 15% of hepatocytes, 70% of LSECs, and 15% of Kupffer cells, significantly improved the ability of iLNPs to actively target LSECs. In contrast, this work indirectly shows that the iLNPs with piperazine head lipid are more able to deliver mRNA to the liver and translate the target protein than the iLNPs with piperidine head lipid. It is worth mentioning that the preparation buffer of 246C10 iLNPs could influence the encapsulation efficiency of mRNA. With the addition of sodium chloride in the citrate buffer, the encapsulation efficiency of CRISPR-Cas9 mRNA and sgRNA was increased. These iLNPs were able to treat hemophilia safely, without causing hepatotoxicity, the immune response induced by Cas9 and off-target editing.

First Inhibitor of PEX14-PEX5 Protein-Protein Interaction (PPI) with Trypanocidal Activity

DSPE-PEG2K-triGalNAc is a polar lipid composed of DSPE and tri-N-acetylgalactosamine that can be used to construct liposomes target to asialoglycoprotein receptor (ASGPR).

Lysophosphatidylcholine 18:2 (1-Linoleoyl-2-Hydroxy-sn-glycero-3-PC), a lysophospholipid, is a potential biomarker identified from insulin resistance (IR) polycystic ovary syndrome (PCOS). Low plasma Lysophosphatidylcholine 18:2 also has been shown to predict impaired glucose tolerance, insulin resistance, type 2 diabetes, coronary artery disease, and memory impairment.

SLW131 (Compound 10) is the antagonist for CCR7 with a good affinity of Ki of 9.85 nM. SLW131 inhibits CCL19-induced Go protein activation with an IC50 of 29.4 μM, inhibits β-arrestin2 recruitment with an IC50 of 6.0 μM. SLW131 inhibits CCL19-induced cell morphological changes in primary BMDCs, and CCR7-mediated migration in mouse CD4+ T cell.

Novel modulator of NF-Y transcription, inhibiting the binding of NF-Y to DNA, blocking cellular proliferation and cell cycle progression, interacting with a variety of CCAAT-containing promoters leading to p53-independent cell cycle arrest

BEN-28010 is a potent selective, orally bioavailable and brain-penetrant checkpoint kinase 1 (CHK1) inhibitor with IC50 of 4 nM, 450-fold selective over CHK2.

NP1867 is a potent, selective, covalent PMS2 inhibitor. NP1867 functionally inhibits DNA mismatch repair. NP1867 enhances immune surveillance. NP1867 can be used in the research of colorectal cancer.

A potent, selective and orally bioavailable TRPV1 receptor antagonist with IC50 of 65 nM and 102 nM for hTRPV1 and rTRPV1, respectively.

CCR7 inhibitor Cmp1205 is an allosteric ligand and antagonist for human CC chemokine receptor 7 (CCR7) with Kd of 3 nM, suppresses arrestin binding in response to activation by CCL19 with IC50 of 7.3 uM.Cmp1205 binds to a pocket at the intracellular part of CCR7 between the ends of TM1, TM2, TM3, and TM6 and the loop between TM7 and H8.Cmp1205 allosterically inhibits binding of the native chemokine CCL19 ligand in a membrane-based competition binding experiment with IC50 of 35 nM.

Trivalent GalNAc-DBCO can be used for oligonucleotide coupling.

ASGPR ligand-1 is a compound that targets the asialoglycoprotein receptor (ASGPR) and is utilized in various disease research contexts .

iDeg-6 is a pseudo-natural product derived from (−)-myrtanol, that inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDeg-1 inhibits kynurenine (Kyn) with IC50 of 16 nM and DC50 of 6.5  nM for IDO1 degradation.

iDeg-1 is a pseudo-natural product derived from (−)-myrtanol, that inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDeg-1 inhibits kynurenine (Kyn) with IC50 of 0.83  µM.

CSN5i-3 is a potent orthosteric molecular glue inhibitor of COP9 signalosome (CSN), functions dually as an orthosteric inhibitor of the iso-peptidase target while simultaneously stabilizing the enzyme–substrate complex as a molecular glue.

HHS-475 is a novel sulfur-triazole exchange (SuTEx) covalent probe with ~5-fold enhanced chemoselectivity for tyrosines over other nucleophilic amino acids.