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.

FTT5 is a lipid-like compound for efficient delivery of long mRNAs in vivo.

KZR-8445 (KZR8445) is a cyclic depsipeptide, client-selective Sec61 inhibitor with IC50 of 100 nM, targets the Sec61 translocon and selectively modulate Sec61-mediated protein biogenesis.

Homoorientin is a potent inhibitor of COX-2 with an IC50 value of 39 μM.

Nanvuranlat (JPH203) is a potent, selective L-type amino acid transporter 1 (LAT1, SLC7A5) inhibitor with IC50 of 60 nM (leucine uptake inhibition), but not LAT2.

IBS007125 is a small molecule inhibitor of c-Maf, inhibits multiple myeloma proliferation by targeting cMaf transcriptional activity.

YSK 05 is a pH-sensitive cationic lipid. YSK 05 improves the intracellular trafficking of non-viral vectors. YSK 05-MEND shows significantly good gene silencing activity and hemolytic activity. YSK 05 overcomes the suppression of endosomal escape by PEGylation. YSK 05 effectively enhances siRNA delivery both in vitro and in vivo.

Nangibotide is a TREM-1 receptor inhibitor that can modulate innate immune response. Nangibotide can reduce systemic and in situ inflammatory reaction in rodent models of myocardial ischaemia‐reperfusion.

TFAX 488,SE dilithium, an amine reactive green fluorescent dye, is insensitive to pH in the range 4-10. TFAX 488,SE dilithium forms bright and photostable conjugates with proteins and antibodies. TFAX 488,SE dilithium is suitable for use in flow cytometry, two-photon excitation microscopy (TPE), and super resolution microscopy techniques, such as dSTORM, SIM and STED. Excitation maximum=495 nm; emission maximum=515 nm; extinction coefficient=73,000 M-1cm-1; quantum yield=0.92.

A potent, long lasting 5-HT(1B/1D) receptor agonist as a antimigraine agent..

MC-GGFG-DX8951 is a drug-linker conjugate for ADC with antitumor activity by using DX8951 (DNA topoisomerase I inhibitor), linked via the protease cleavable MC-GGFG linker.

Rhodamine 123 is a chemical compound and a dye.

OG 488, acid, a fluorescent pH indicator, has many applications in biochemistry and neurosciences.

HCQ-2 NHS is a dark quencher with no native emission due to the polyaromatic-azo backbone and a terminal NHS ester. UBHQ-2 NHS has a wide and intense quenching range from 560-670 nm, which makes it useful as an acceptor in fluorescence resonance energy transfer (FRET) applications in conjunction with orange to far-red emitting dyes. The NHS ester can be applied to label the primary amines (-NH2) of proteins, amine-modified oligonucleotides, and other amine-containing molecules.

5-FAM SE is a single isomer, it is one of the most popular green fluorescent reagents used for labeling peptides, proteins and nucleotides.

Fluorescein isothiocyanate(FITC) is a derivative of fluorescein used in wide-ranging applications including flow cytometry.

JZL184 is a strong and selective inhibitor of Monoglyceride Lipase

YO-01027 (Dibenzazepine, DBZ) is a dipeptidic g-secretase inhibitor with IC50 of 2.6 and 2.9 nM for APPL and Notch, respectively.

CeMMEC13 is a potent inhibitor of TAF1 (2) bromodomain, with an IC50 of 2.1 μM.

E-64c is a synthetic analog of E-64, a potent and irreversible cysteine protease inhibitor isolated from Aspergillus japonicus.

OPC-21268 is a vasopressin 1 receptor antagonist potentially for the treatment of heart failure and hypertension.

Bay K-8644 is a potent L-type calcium channels (LTCCs) activator with EC50 of 17.3 nM, has positive inotropic, vasoconstrictive and behavioral effects in vivo.

Dp44mT is a potent iron chelator, which shows selective antitumor activity.

Azoramide is a small-molecule modulator of the unfolded protein response with antidiabetic activity.

Pico145 is a highly potent, subtype-selective TRPC1/4/5 channels inhibitor with potency ranged from 9 to 1300 pM, depending on the TRPC1/4/5 subtype and activation mechanism.

POL1-IN-1 is a RNA polymerase 1 (POL1, also known as Pol I) inhibitor with an IC50 of less than 0.5 uM. POL1-IN-1 inhibits ribosome biogenesis by inhibiting POL1 transcription.

A highly potent, selective, orally available Src family kinase inhibitor with IC50 of <0.5 nM, <0.5 nM and for Src, Yes and Fyn kinases respectively, >950-fold selectivity for Src over ABL.

Traumatic Acid is a monounsaturated dicarboxylic acid isolated from  Phaseolus vulgaris. Traumatic Acid can cause a decrease in membrane phospholipid peroxidation and show antioxidant and stimulatory effects on collagen biosynthesis. Traumatic Acid is a potential agent for the treatment of many skin diseases connected with collagen biosynthesis disorders and oxidative stress.

NERx 329 (RPAi 329, NERx329) is a novel potent, specific inhibitor of replication protein A (RPA), demonstrated potent RPA inhibitory activity in vitro, in vivo, and in cellular assays.

AZD 4205 (AZD4205) is a potent, selective JAK1 inhibitor IC50 of 73 nM and Ki of 2.8 nM, shows high selectivity against JAK2 and JAK3 with IC50 of 13,233 nM and >30,000 nM respectively; shows potent inhibition of p-STAT3 in a cell based assay of JAK1 activity with an IC50 of 128 nM and excellent selectivity across the kinome; reduces residual disease and prolongs the benefit of Osimertinib in lung cancer patients with EGFR activating mutations both in vitro and in vivo.