Amenamevir, also known as ASP2151, is a herpes virus helicase-primase inhibitor.

A pan-RAR inverse agonist that blocks RARα activity with IC50 of 114 nM.

DAPT(GSI-IX) is an inhibitor of γ-secretase; DAPT causes a reduction in Aβ40 and Aβ42 levels in human primary neuronal cultures (IC50 values are 115 and 200 nM for total Aβ and Aβ42 respectively) and in brain extract, cerebrospinal fluid and plasma.

AH001 is a orally active RhoA inhibitor, which binds a cryptic pocket proximate to GDP within RhoA with a KD of 73.16 nM. AH001 interacts with GDP, stabilizing RhoA’s interaction with its endogenous inhibitor, RhoGDIα. AH001 reduces the downstream MRTFA nuclear translocation and downregulates fibrosis/hypertrophy proteins. AH001 mitigates myocardial remodeling in multiple HF animal models, and in the 3D myocardial tissue model. AH001 exerts its cardioprotective effects through the RhoA-RhoGDIα axis, effectively inhibiting downstream RhoA activation signaling.

CTOP is a potent and highly selective μ-opioid receptor antagonist. CTOP antagonizes the acute morphine-induced analgesic effect and hypermotility. CTOP enhances extracellular dopamine levels in the nucleus accumbens. CTOP dose-dependently enhances locomotor activity.

EVT0185 is an orally active ATP citrate lyase (ACLY) inhibitor. EVT0185 is converted to a CoA thioester in the liver by SLC27A2 and interacts with the CoA-binding site of ACLY. EVT0185-CoA inhibits ACLY activity with an IC50 of 2.5 μM. EVT0185 can phenocopy the immune and antitumour effects of genetic ACLY deletion. EVT0185 can increase tumour-infiltrating B cells and chemokine CXCL13 levels. EVT0185 can be used for the research of cancer, such as hepatocellular carcinoma (HCC).

Abarelix is a synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix directly and competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with prostate hypertrophy or prostate cancer, since testosterone is required to sustain prostate growth.

NuP-3 is a potent and selective MAPK13 and MAPK14 inhibitor (IC50 of 7 nM and 14 nM, respectively) that effectively targets respiratory inflammation and mucus overproduction. In human tracheal epithelial cell (hTEC) cultures, it markedly inhibits IL-13-induced MUC5AC and CLCA1 expression without causing cell toxicity, showing superior efficacy compared to the MAPK14 inhibitor NuP-43. Beyond its success in minipig models of airway disease and viral infection, NuP-3 also down-regulates biomarkers associated with basal-epithelial stem cell activation, demonstrating its role as a precise upstream therapeutic agent for chronic lung conditions.

BPH-1358 free base (NSC50460 free base) is a potent human farnesyl diphosphate synthase (FPPS) and undecaprenyl diphosphate synthase (UPPS) inhibitor with IC50s of 1.8 μM and 110 nM, respectively, and is active against S. aureus in vitro (MIC ~250 ng/mL).

BPH-1358 mesylate (NSC50460 mesylate) is a potent human farnesyl diphosphate synthase (FPPS) and undecaprenyl diphosphate synthase (UPPS) inhibitor with IC50s of 1.8 μM and 110 nM, respectively. BPH-1358 mesylate is active against S. aureus in vitro (MIC ~250 ng/mL).

Fosaprepitant, also known as MK0517, is an antiemetic drug, administered intravenously. It is a prodrug of aprepitant. Fosaprepitant was developed by Merck & Co. and was approved. It is a prodrug of Aprepitant. It aids in the prevention of acute and delayed nausea and vomiting associated with chemotherapy treatment. Fosaprepitant is a weak inhibitor of CYP3A4, and aprepitant, the active moiety, is a substrate, inhibitor, and inducer of CYP3A4

T0080 is a FPR-1 antagonist. T0080 reduces the cell apoptosis, inhibits ROS production and pro-inflammatory cytokines (TNF-α and IL-1β) from plaque macrophages, which attenuates atherosclerotic progression in ApoE−/− mice.

MitoCKi (Creatine kinase inhibitor CKi-26) is a selective, covalent inhibitor of creatine kinases (CKs), inhibits recombinant creatine kinase B (CKB) phosphotransfer activity with IC50 of 185 nM, depletes creatine phosphagen energetics in cells.

GSK 525762A is a potent small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4).

A novel potent, selective, allosteric and orally active dopamine D1 receptor potentiator with Kb of 26 nM.

GSK-3923868 (PI4KB inhibitor 30) is a potent, selective, slow-dissociating PI4KB (PI4kIII-beta) inhibitor with pKi of 9.8, >1000-fold selectivity over PI4KA, inhibits HRV viral replication in COPD BECs.

T26A is a competitive prostaglandin transporter (PGT) inhibitor (Ki=378 nM). T26A is promising for research of prostaglandin signaling and inflammatory diseases (e.g., glaucoma, pulmonary hypertension) .

HQY426 is a specific, orally bioavailable inhibitor of pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3) with binding IC50 of 0.32 uM, exhibits potent antitumor activity.

LDN-0130436 is a novel TDP-43::GFP aggregation inhibitor.

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

KDOBA67 is a novel cell-permeable inhibitor of H3K27 lysine demethylase KDM6A/B, inhibits TBXT expression chordoma cell lines.KDOBA67 displayed in vitro inhibitory activity in the low micromolar range with IC50 values of 2 to 5 uM in various chordoma cell lines, leading to induction of apoptosis.H3K27 demethylase inhibition via KDOBA67 alters chromatin state at TBXT and inhibits its expression.TBXT was a KDM6A/B target gene, and chromatin changes at TBXT following KDOBA67 treatment were associated with a reduction in TBXT protein levels.KDOBA67 treatment downregulated expression of a network of transcription factors critical for chordoma survival and upregulated pathways dominated by ATF4-driven stress and proapoptotic responses.

Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. Cyclovirobuxine D induces autophagy and attenuates the phosphorylation of Akt and mTOR. Cyclovirobuxine D inhibits cell proliferation of gastric cancer cells through suppression of cell cycle progression and inducement of mitochondria-mediated apoptosis. Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction.

MN132.0262 is a small molecule, dual inhibitor of A3G (APOBEC3G, IC50=20 uM).

MN256.0102 is a small-molecule APOBEC3G DNA cytosine deaminase inhibitor with IC50 of 3.9 uM.

UNC10013 is a SETDB1 allosteric modulator that forms a covalent bond with Cys385 in the 3TD domain, exhibiting negative allosteric regulatory activity. It has a kinact/KI value of 1.0 × 106 M-1*s-1. UNC10013 effectively disrupts SETDB1-mediated Akt methylation and holds potential value for research in cancer and neurodegenerative diseases.

AF12198 is a potent, selective and specific peptide antagonist for human type I interleukin-1 receptor (IL1-R1) (IC50=8 nM) but not the human type II receptor (IC50=6.7 μM) or the murine type I receptor (IC50>200 μM). AF12198 inhibits IL-1-induced IL-8 production (IC50=25 nM) and IL-1-induced intercellular adhesion molecule-1 (ICAM-1) expression (IC50=9 nM) in vitro. AF12198 has anti-inflammatory activities and?blocks responses to IL-1 in vivo.

A-1331852 is a high affinity BH3 mimetic Ligand of BCL protein BCL-XL.

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