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.

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.

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.

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.

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%.

STING inhbiitor, which inhibited the activation of the STING signal pathway and to prevent or treat a STING-​mediated disease.

RO5126766(CH5126766) is a Raf/MEK dual kinase inhibitor.

GSK898 is a potent, highly selective kynurenine monooxygenase (KMO) inhibitor with pIC50 of 8.8.

seMpai is a high-performance near-infrared (NIR) luciferin analogue engineered for enhanced deep-tissue bioluminescence imaging, producing a robust 675 nm emission comparable to top-tier substrates. In vitro, it effectively supports mutant luciferase systems like Akaluc, while in vivo, it enables detection of pulmonary micro-metastases, overcoming traditional D-luciferin limitations. The compound features an optimized, neutral pH formulation that reduces hepatic background, ensuring superior signal-to-noise ratios without significant toxicity, making it ideal for longitudinal studies. For optimal solubility and performance, seMpai is a critical tool for preclinical imaging and drug discovery. Learn more at MedKoo. NOTE. seMpai (Cat#465342) is the free acid form and is less water soluble. seMpai Sodium (CAT#333158) is water soluble.

YXN47931, also known as Paclitaxel succinate sulfo-NHS ester, is a paclitaxel derivative with a succinic acid linker, in which the carboxy group is activated with an sulfo-NHS ester. The sulfo-NHS ester group is highly reactive to amino group or hydroxy group, and can be used to conjugate with other molecules such as peptides, proteins, antibodies or enzymes, or polymers. Paclitaxel-Succinic acid is a useful agent to make Paclitaxel-conjugate for drug delivery, nanodrug research. Note: Paclitaxel-Succinic acid (CAT#620101), Paclitaxel-Succinate-NHS (also called DCN10809, CAT#408092) are also in stock. This product has no formal name at the moment. For the convenience of communication, a temporal code name was therefore proposed according to MedKoo Chemical Nomenclature (see web page: https://www.medkoo.com/page/naming). NOTE: YXN47931 sodium (CAT#408203) is water soluble. YXN47931 free acid (CAT#408211) has very low solubility in water.

AM-001, a small-molecule EPAC1 (exchange protein directly activated by cAMP) inhibitor, showed potent in vitro antiviral activity against SARS-CoV-2 and influenza A in cultured cells. In Vero E6 cells, AM-001 reduced SARS-CoV-2 viral RNA and infectious titres with IC₅₀ ≈ 355–388 nM and in human lung Calu-3 cells with IC₅₀ ≈ 147–167 nM, achieving ~10⁴-fold suppression at 20 µM without cytotoxicity (CC₅₀ > 40 µM; selectivity index >100). AM-001 also inhibited influenza A replication in Calu-3 cells with IC₅₀ ~1 µM. These effects reflect host-targeted EPAC1 inhibition rather than direct virucidal action. No in vivo animal model data were included in the study’s antiviral evaluation.

CT-996 is an orally active GLP-1RA agonist, with an EC50 of 0.49 nM. CT-996 reduces the β-arrestin recruitment and GLP-1R internalization. CT-996 suppresses postprandial blood glucose following a mixed meal tolerance test (MMTT) in mice expressing the human GLP-1 receptor and enhances glucose stimulated insulin secretion (GSIS) during an intravenous glucose challenge in obese monkeys. CT-996 can be used for the study of type 2 diabetes (T2D) and obesity.

Selumetinib (AZD6244) is selective, non-ATP-competitive oral MEK1/2 inhibitor, with an IC50 of 14 nM for MEK1. Selumetinib (AZD6244) inhibits ERK1/2 phosphorylation.

Opitor-0 is a potent and selective inhibitor of the mitochondrial GTPase Optic atrophy protein 1 (OPA1) with an IC50 of approximately 3 µM. In cellular studies, Opitor-0 disrupts OPA1 oligomer stability, leading to mitochondrial fragmentation and remodeling of mitochondrial cristae. These structural changes facilitate the release of Cytochrome c from mitochondria into the cytosol, triggering apoptotic signaling. The compound exhibits significant pro-apoptotic and antitumor effects in cancer cell models. Importantly, Opitor-0 demonstrates strong synergistic activity with Bcl-2 inhibitors such as ABT-737 and Venetoclax, enhancing tumor cell death. These results suggest that Opitor-0 effectively targets mitochondrial dynamics and apoptosis pathways in cancer cells.

DOTA-GPC3 is a ligand for radiotracer targeting glypican GPC3 . DOTA-GPC3 molecule is consisted of a chelator DOTA for radioactive metal ions and a GPC targeting peptide for binding glypican GPC3. Glypican-3 (GPC3) is highly expressed in HCC but not in normal liver tissue, making it a promising target for PET-based molecular imaging, which may complement existing approaches for HCC diagnosis.

Moxonidine (BDF5895) hydrochloride is an orally active imidazoline type 1 receptor (I1-R) agonist. Moxonidine hydrochloride activates imidazoline I1 receptors and α2 adrenoceptors, affecting oxidized low-density lipoprotein uptake. Moxonidine hydrochloride reduces atherosclerotic lesions and lowers blood pressure. Moxonidine hydrochloride can be used in the study of hypertension, heart failure, and atherosclerosis.

DPI-4452 is a CAIX-targeting cyclic peptide with a DOTA chelator. DPI-4452 can be chelated with radionuclide for CAIX-expressing tumor PET-CT imaging. DPI-4452 was used to prepare [68Ga]Ga-DPI-4452, which is a first-in-class carbonic anhydrase IX-binding radiolabeled peptide, and is the imaging agent of a theranostic pair with [177Lu]Lu-DPI-4452, developed for selecting and treating patients with carbonic anhydrase IX-expressing tumors. [68Ga]Ga-DPI-4452 showed exceptional tumor uptake in patients with clear cell renal cell carcinoma, with very high tumor-to-background ratios and no significant adverse events, suggesting potential diagnostic and patient selection application.

Mortaparib is a dual inhibitor of mortalin-PARP1 interaction, and a p53 activating cytotoxic compound, induces activation of growth arrest and apoptosis signaling in cancer cells in vitro and in vivo.