Simepdekinra (Compound 221) is a IL-17A modulator with IC50s ≤10  nM and 10-100 nM for IL-17A/A HEK-Blue and IL-17A/F HEK-Blue cells. Simepdekinra can be used for inflammatory diseases such as psoriasis, ankylosing spondylitis and psoriatic arthritis research.

PA-915 (PA915) is a small-molecule, non-peptide antagonist of the PACAP type I (PAC1) receptor, inhibits PACAP (1 nM)-induced phosphorylation of CREB in PAC1/CHO cells with IC50 of <10 pM.

A derivative of the neurotransmitter GABA that acts as a GABAB receptor agonist.

GYS32661 is a potent, small-molecule inhibitor of RAC1 and its isoform RAC1B, specifically designed to target the Sonic Hedgehog (Shh) signaling pathway in cancers like medulloblastoma and colorectal carcinoma. Distinguishing itself from other RAC1 inhibitors, GYS32661 exhibits exceptional blood-brain barrier (BBB) permeability with an approximately 50% brain-to-plasma ratio, making it a premier candidate for treating CNS-related malignancies. It functions by disrupting the activation of RAC1 (IC50 ≈ 1.18 μM), subsequently reducing the expression of downstream transcription factors GLI1 and GLI2, which effectively halts tumor proliferation and metastasis. In preclinical in vivo models, the compound has demonstrated significant anti-tumor efficacy and a favorable safety profile without systemic toxicity. Due to its hydrophobic nature, it is typically formulated in a vehicle of DMSO, PEG300, and saline for administration. As a non-toxic clinical candidate, GYS32661 represents a promising therapeutic strategy for overcoming chemoresistance and improving survival rates in Shh-driven pediatric and adult tumors.

LY2334737 is an orally available prodrug of gemcitabine which is a nucleoside analog used as chemotherapy.

DF-003 is a selective, orally active, ATP-competitive, and brain-penetrant ALPK1 inhibitor. DF-003 potently inhibits human ALPK1 and ALPK1[T237M] with IC50s value of 1.5 nM and 16 nM. DF-003 exhibits more than 860-fold selectivity over the closest kinase. DF-003 inhibits TNF, CXCL10, or CXCL8 upregulation in HEK-293 cells. DF-003 can be used for the study of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome.

RSL3-NH2 is a GPX4 inhibitor and Ferroptosis inducer. RSL3-NH2 can be used as a cytotoxic payload for synthesis of antibody-drug conjugates (ADCs).

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

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.

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.

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

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.

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.

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

SLW131 (Compound 10) is the antagonist for CCR7 with a good affinity of Ki of 9.85 nM. SLW131 inhibits CCL19-induced Go protein activation with an IC50 of 29.4 μM, inhibits β-arrestin2 recruitment with an IC50 of 6.0 μM. SLW131 inhibits CCL19-induced cell morphological changes in primary BMDCs, and CCR7-mediated migration in mouse CD4+ T cell.

Novel modulator of NF-Y transcription, inhibiting the binding of NF-Y to DNA, blocking cellular proliferation and cell cycle progression, interacting with a variety of CCAAT-containing promoters leading to p53-independent cell cycle arrest

A potent, selective and orally bioavailable TRPV1 receptor antagonist with IC50 of 65 nM and 102 nM for hTRPV1 and rTRPV1, respectively.

HHS-475 is a novel sulfur-triazole exchange (SuTEx) covalent probe with ~5-fold enhanced chemoselectivity for tyrosines over other nucleophilic amino acids.

ATN-224 is a choline salt of tetrathiomolybdate and an inhibitor of superoxide dismutase 1 (SOD1; IC50s = 2.91 and 3.51 µM in human and mouse blood cells, respectively, in vitro).