Novel agonist of the water channel aquaporin-1 (AQP1)

VU0238441 is a pan muscarinic acetylcholine receptor (mAChR) positive allosteric modulator (PAM) with EC50s of 3.2 μM, 2.8 μM, 2.2 μM, 2.1 μM, >10 μM for M1, M2, M3, M5 and M4, respectively.

NuP-3 is a potent, selective MAPK13 and MAPK14 inhibitor with IC50 of 7 and 14 nM, respectively.

JXL069 is a novel mitochondrial pyruvate carrier (MPC) inhibitor being investigated for its therapeutic potential in treating alopecia and hair growth disorders.

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.

A potent inhibitor of tumor promoting phorbol ester TPA/PMA and inhibitor of Ca2+/calmodulin dependent EF-2 phosphorylation

ProSeAM is a chemical tool for methylome analysis.

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.

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.

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

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.

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).

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.

DOIC is a cationic lipid that can be used for RNA vaccines.

Leucettinib-21 is a highly selective and potent dual inhibitor targeting both DYRK and CLK kinase families. It demonstrates nanomolar-level inhibitory activity, with IC50 values of 2.4 nM (DYRK1A), 6.7 nM (DYRK1B), 12 nM (CLK1), 33 nM (CLK2), and 5 nM (CLK4), respectively. This compound exhibits remarkable kinase selectivity, making it a valuable pharmacological tool for studying these kinase-mediated pathways.

UHMCP1 is a small molecule that prevents the SF3b155/U2AF65 interaction, binds to the hydrophobic pocket of the U2AF65 UHM domain (Kd=1-20 uM), impacts splicing and cell viability.

Novel pendrin inhibitor, inhibiting Cl-/anion exchange mediated by mouse pendrin without affecting other major kidney tubule transporters

Amastatin HCl is an aminopeptidase inhibitor that also induces vasoconstriction.

BI-8128 is a potent, selective, reversible and orally bioavailable fourth generation EGFR inhibitor, potently inhibits oncogenic EGFR variants del19 and L858R as well as the acquired EGFR resistance mutations T790M and C797S.

Phenylacetylglutamine is used as biomarker for metabolic age.

DC-LC3in-D5 acts as an autophagy inhibitor by attenuating LC3B lipidation. DC-LC3in-D5 binds with LC3B. DC-LC3in-D5 disrupts the LC3B-LBP2 interaction with an IC50 of 200 nM. DC-LC3in-D5 may contribute to anti-HCV or combination treatments in cancer through inhibiting autophagy.

ER-464195-01 is a specific, orally active inhibitor that inhibits Calreticulin (CRT) binding to integrin α subunits (ITGAs) with IC50 of 0.17, 0.36, and 0.23 uM in the interaction between CRT and ITGA α4, αL, and αM/α2/α5.

AGF347 (AGF-347) is a small molecule inhibitor targeting mitochondrial C1 metabolism at SHMT2 (in vitro Ki=2.19 uM), also directly targers the purine biosynthetic enzymes GARFTase (Ki=3.13 uM) and AICARFTase (Ki=3.72 uM), and SHMT1 (Ki=2.91 uM).

Galvestine-1 is a small molecule MGDG (monogalactosyldiacylglycerol) synthase inhibitor with IC50 of 10 uM by competing with diacylglycerol binding.

2-Furoyl-LIGRLO-amide is a potent and selective proteinase-activated receptor 2 (PAR2) agonist with a pD2 value of 7.0.

A small molecule inhibitor of diacylglycerol kinase (DGK) with IC50 of 2.8 uM, inhibits the phosphorylation of OAG to OAPA with IC50 of 3.8 uM in intact platelets.

LBL1 is a first-in-class pyrroloquinazoline small molecule that selectively targets the coiled-coil domain of lamin A (binding affinity Kd = 5.11 μM), demonstrating potent anticancer effects through nuclear lamina disruption.

SD-36 (STAT3 degrader SD-36) is a potent, selective STAT3 degrader (PROTAC), potently induces the degradation of STAT3 protein in vitro and in vivo.SD-36 is designed using an analogue of CRBN ligand lenalidomide and the STAT3 inhibitor SI-109, binds to recombinant STAT3 protein with Ki of 11 nM.SD-36 (250 nM) depleted >90% of STAT3 protein in MOLM-16 cells after 4 hr treatment and >50% of STAT3 protein in DEL, KI-JK and SU-DHL-1 cells after 7 hr treatment, also efficiently degraded STAT3 protein in murine cells.SD-36 displays extremely high cellular selectivity for degradation of STAT3 over other STATs.SD-36 effectively degrades both wild-type and mutated STAT3 proteins in cells, effectively degrades mutated STAT3 (D661Y, K658R mutant), also effectively degrades CRISPR-mutated homozygous Y705F mutant STAT3 protein in DLD-1/STAT3Y705F/Y705F cells.SD-36 displayed strong growth-inhibitory activities in a subset of leukemia and lymphoma cell lines (MOLM-16 cell line IC50, 35 nM), 100-fold more potent than SI-109.SD-36 (i.v. 25 mg/kg) effectively and selectively depletes STAT3 protein, achieves complete and long-lasting tumor regression in in mouse xenograft tumors.

ARV-110 is an orally active, specific androgen receptor (AR) PROTAC degrader. ARV-110 promotes ubiquitination and degradation of AR. ARV-110 can be used for the research of prostate cancer.

ARV471 is an orally bioavailable estrogen receptor-targeting (ER-targeting) PROTAC for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.