D-MoDE-A (1) is a bifunctional small molecule that mediates the degradation of extracellular proteins through the asialoglycoprotein receptor (ASGPR).

tri-GalNAc-COOH acetylation is the acetylated and modified form of tri-GalNAc-COOH. tri-GalNAc-COOH acetylation can be used for the synthesis of LYTAC.

Tri-GalNAc-NHS ester is a LYsosome TArgeting Chimera (LYTAC) and a ligand of asialoglycoprotein receptor (ASGPR). ASGPR is a lysosomal targeting receptor specifically expressed on liver cells, for the degradation of extracellular proteins including membrane proteins. Tri-GalNAc-NHS ester can be used as a protein degrader and it can be used for the research of LYTAC.

tri-GalNAc-COOH is an asialoglycoprotein receptor (ASGPR) ligand that can be used for LYsosome TArgeting Chimera (LYTAC) research.

VRK-IN-1 is a potent and selective inhibitor of vaccinia-related kinases 1 (VRK1), with an IC50 of 150 nM. VRK1 is human Ser/Thr protein kinases associated with increased cell division and neurological disorders.

Vicadrostat (compound 29 A) is a potent and selective inhibitor of aldosterone synthase(CYP11B2) with an IC50 of 16 nM. It exhibits potential in renal disease, diabetic nephropathy, cardiovascular diseases and fibrotic disorder research.

Barbadin is a small molecule that selectively inhibits the β-arrestin/β2-adaptin interaction (IC50=19.1/15.6 uM for β-arrestin1/2) without effect on the formation of receptor/β-arrestin complexes.

Olorofim (F901318) selectively inhibits fungal dihydroorotate dehydrogenase (DHODH), a key enzyme in the pyrimidine biosynthesis pathway. Olorofim (F901318). Olorofim exhibits excellent activity against A. fumigatus and other Aspergillus spp.

AUR1545 is a selective degrader of KAT2A and KAT2B. AUR1545 can be used in the cancer research, including studies on AML (Acute myeloid leukemia), SCLC (Small-cell carcinoma), and NEPC (Neuroendocrine Prostate Cancer).

T025 is as an orally available and potent inhibitor of Cdc2‐like kinases (CLKs) with an IC50s of 0.93 nM, 1 nM, 14 nM, 1.5 nM for CLK1, CLK2, CLK3, DYRK1B respectively. It exhibits anti‐tumor efficacy and can be used in MYC‐driven cancer research.

(3S) ALG-05 is a potent pan-inhibitor of gut microbia tryptophan-indole-lyases (TILs, E.C. 4.1.99.1), exhibits inhibitory activity across TILs with Ki of 7-11 uM.

Sitagliptin, also known as MK-0431, is a potent inhibitor of DPP4 with an IC50 of 19 nM in Caco-2 cell extracts. Sitagliptin is believed to exert its actions in patients with type 2 diabetes mellitus by slowing the inactivation of incretin hormones. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

OV329 (OV 329) is a highly potent inactivator of gamma-aminobutyric acid aminotransferase (GABA-AT) with Ki of 9.69 uM.

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs used as an anti-inflammatory and immunosuppressant.

Novel Sirtuin1 Activator, Down-Regulating Sclerostin and Rescuing Ovariectomy-Induced Bone Loss

ARC39 is acid sphingomyelinase inhibitor (IC50 =20 nM).

Icotrokinra (JNJ-77242113, JNJ-2113, PN-235) is an orally available and selective antagonist of the IL-23 receptor. It also inhibits IL-23–induced STAT3 phosphorylation in peripheral blood mononuclear cells with an IC50 of 5.6 pM and suppresses IL-23–induced IFN-γ production in NK cells with an IC50 of 18.4 pM. It also exhibits anti-inflammatory activity in a TNBS-induced colitis model in rats and holds potential for studying psoriasis, psoriatic arthritis, and inflammatory bowel disease.

NMS-P293 (also known as NMS-03305293) is an innovative, second-generation oral small molecule inhibitor specifically targeting PARP1. Developed by Nerviano Medical Sciences, it distinguishes itself from first-generation PARP inhibitors through its high selectivity for PARP1 over PARP2, which significantly reduces hematological toxicities like bone marrow suppression.A defining feature of NMS-P293 is its non-trapping mechanism; by inhibiting enzyme activity without trapping PARP on DNA, it offers a superior safety profile that allows for effective combination with DNA-damaging chemotherapies. Furthermore, it possesses exceptional blood-brain barrier (BBB) permeability, making it a leading candidate for treating primary CNS tumors like glioblastoma and brain metastases.

A potent, selective inhibitor of HIV integrase (IC50=8-15 nM) with potent antiviral activity in cell culture and good pharmacokinetic properties.

Secreted frizzled-related protein-1 (sFRP-1) modulaitor

NCGC00685960 is a Nicotinamide N-methyltransferase (NNMT) inhibitor with an IC50 < 10  nM. NCGC00685960 has potent antitumor activity. NCGC00685960 increases H3K27 trimethylation levels in ovarian cancer cells and inhibits α-SMA expression in NNMT-expressing ovarian fibroblasts. NCGC00685960 reduces 1-MNA levels, reverses SAM and H3K27 hypomethylation and significantly impairs collagen contractility in cancer-associated fibroblasts (CAFs). NCGC00685960 can be used for cancers research.

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.

503O13 is a next-generation, biodegradable lipid nanoparticle (LNP) engineered for highly efficient and targeted siRNA delivery. Designed through rational structure-activity criteria—including optimal tail length (O13), tertiary amines, and a surface pKa ≥5.5—this single-component LNP achieves unparalleled gene silencing with an ultra-low EC50 of 0.01 mg/kg in preclinical models.503O13 outperforms non-degradable counterparts (e.g., C12-200) with improved toxicity profiles—no hepatic necrosis or pancreatic inflammation—while maintaining rapid blood clearance (t1/2: 6 min) and organ-specific accumulation (liver/spleen).

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.

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.

IC8 is an ionizable cationic lipid. It has been used in combination with other lipids for the formation of lipid nanoparticles (LNPs). Immunization with severe acute respiratory coronavirus 2 (SARS-CoV-2) spike glycoprotein mRNA in IC8- and manganese-containing LNPs induces IgG responses to SARS-CoV-2 Delta and Omicron variants in mice.1 Administration of mRNA encoding B7-H3 X CD3 bispecific T cell engaging (BiTE) antibodies in IC8-containing LNPs reduces tumor growth in MV4-11 and A375 mouse xenograft models.

PAANIB-1 is a brain-penetrant PAAN/MIF nuclease inhibitor that prevents neurodegeneration that prevents neurodegeneration induced by α-syn PFF, AAV-α-syn overexpression, or MPTP intoxication in vivo.

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

CLinDMA, a cationic lipid known to potentially trigger inflammatory responses, is utilized in the synthesis of LNP201. This liposome-based assembly is specifically designed for the systemic delivery of siRNA.

QC-01-175 is a hetero-bifunctional molecule designed to engage both tau and Cereblon (CRBN) to trigger tau ubiquitination and proteasomal degradation (tau PROTAC).QC-01–175 effected clearance of tau in frontotemporal dementia (FTD) patient-derived neuronal cell models, with minimal effect on tau from neurons of healthy controls.QC-01–175 also rescued stress vulnerability in FTD neurons, phenocopying CRISPR-mediated MAPT-knockout.