hgc

Glutaminyl Cyclase Inhibitor 3, a designed anti-Alzheimer's compound, is a potent human Glutaminyl Cyclase (GC) inhibitor (IC50: 4.5 nM). It significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions.

HGC652 is a molecular glue that targets the E3 ubiquitin ligase TRIM21, facilitating the formation of a ternary complex between TRIM21 and NUP98, which induces the degradation of NUP155 and nuclear pore complex proteins, ultimately leading to cell death. HGC652 inhibits the proliferation of various cancer cells, with its antiproliferative activity depending on the expression level of TRIM21.

HgCht2-IN-1 (compound 1516b) is an HgCht2 inhibitor that effectively suppresses the antagonistic effect of cyst nematodes on nitrogen-fixing rhizobia and phosphorus-absorbing arbuscular mycorrhizal symbioses. It is applicable for research involving the microbial symbiosis antagonism by cyst nematodes.

Pevonedistat (MLN4924) is a potent and selective NEDD8 activating enzyme (NAE) inhibitor (IC50=4.7 nM) with therapeutic potential for myelodysplastic syndromes (MDS) and antitumor activity.

Dihydroartemisinin (Artenimol) is an antimalarial drug.

MAPK-IN-3 (Compound 4a) is an antiproliferative agent demonstrating significant inhibitory effects on KYSE 30, HCT 116, and HGC 27 cell lines, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. This compound arrests the cell cycle via a p53-dependent mechanism and induces apoptosis through a p53-independent pathway. It reduces the expression of cell cycle-related proteins, such as Cyclin D1 and Cyclin B1, while increasing pro-apoptotic proteins like cleaved PARP, cleaved caspase-7, and cleaved caspase-9. MAPK-IN-3 also decreases anti-apoptotic proteins such as Bcl-2, elevates ROS levels in KYSE 30 cells, and enhances the expression of ROS-related MAPK pathway members, including p-ERK, p-p38, and p-JNK.

Tubulin polymerization-IN-76 (compound 20b) is a potent and orally active inhibitor of tubulin polymerization. It acts at the colchicine binding site to inhibit tubulin polymerization with an IC50 value of 2.505 μM, effectively disrupting the intracellular microtubule network and interfering with mitosis. Tubulin polymerization-IN-76 shows significant inhibitory effects on MGC-803 and HGC-27 cells, with IC50 values of 1.61 and 1.82 nM, respectively. It effectively suppresses colony formation and cell migration activities in these cell lines, inducing G2/M phase cell cycle arrest and apoptosis (Apoptosis). Furthermore, Tubulin polymerization-IN-76 exhibits broad-spectrum antiproliferative activity.

PI3K-IN-52 (compound cis 6g) is a potent PI3K inhibitor with an IC50 of 0.23 μM in HGC-27 cells. It plays a significant role in cancer research.

PROTACPI3Kα degrader-1 is a PI3Kα-targeting PROTAC degrader (DC50= 0.08 μM) that demonstrates notable selectivity in degrading PI3Kα over the PI3Kβ, PI3Kγ, and PI3Kδ isoforms. It degrades PI3Kα effectively in a time- and concentration-dependent manner and significantly inhibits the phosphorylation of AKT at the Ser473 site. Additionally, PROTACPI3Kα degrader-1 exhibits significant in vivo anticancer efficacy in HGC-27 and DOHH2 xenograft models.

VEGFR-2-IN-71 is a dual inhibitor of VEGFR2/tubulin. It suppresses tumor cell proliferation, induces apoptosis and cell cycle arrest, and inhibits angiogenesis in the chicken embryo chorioallantoic membrane (CAM) model. By targeting VEGFR2 and tubulin, VEGFR-2-IN-71 hinders tumor growth in the HGC-27 xenograft model. It exhibits low oral bioavailability in rats and is applicable in cancer research.

Myceliothermophin E is a polyketide-amino acid hybrid fungal metabolite that has been found inT. thermophilusand has anticancer and antimicrobial activities.1,2It is cytotoxic to DLD-1, Hep3B, HepG2, and HGC-27 cancer cells (IC50s = 0.32, 0.42, 0.26, and 0.08 μg/ml, respectively).1Myceliothermophin E is active against methicillin-resistant, but not -sensitive,S. aureus(MICs = 15.8 and >100 μM, respectively).2 1.Gao, Y.-L., Zhang, M.-L., Wang, X., et al.Isolation and characterization of a new cytotoxic polyketide-amino acid hybrid from Thermothelomyces thermophilus ATCC 42464Nat. Prod. Res.Epub ahead of print(2019) 2.Wang, X., Zhao, L., Liu, C., et al.New tetramic acids comprising of decalin and pyridones from Chaetomium olivaceum SD-80A with antimicrobial activityFront. Microbiol.102958(2020)

Antitumor agent-53 is a potent compound that inhibits tumor growth by inducing G2/M cell cycle arrest and promoting apoptosis in HGC-27 cells through PI3K/AKT pathway inhibition. It shows promise for further research in gastrointestinal tumor treatment [1].

GRPR antagonist-1 is a potent antagonist of the gastrin-releasing peptide receptor (GRPR) and displays cytotoxicity to certain cancer cells, including PC3 cells (IC50: 4.97 μM), Pan02 cells (IC50: 4.36 μM), and HGC-27 cells (IC50: 3.40 μM). It reduces Bcl-2 levels, increases Bax levels, inhibits HGC-27 cell viability, and induces apoptosis, thereby exhibiting anti-cancer effects.

GRPR antagonist-2 is a potent antagonist of the gastrin-releasing peptide receptor (GRPR) and exhibits anticancer effects with cytotoxicity to HGC-27 cells (IC50: 0.77 μM) and Pan02 cells (IC50: 2.5 μM).

SC10914 is a highly potent PARP inhibitor (PARP1 IC50 = 7.87 nM) with potent anti-proliferative activity against human BRCA deficient tumor cells (MDA-MB-436, BRCA1 deficient, IC50 = 4.03 nM, Capan-1 BRCA2 deficient, IC50 = 11.66 nM) and PTEN deficient tumor cells (HGC-27,PTEN deficient, IC50 = 0.35 μM). SC10914 showed potent anti-tumor activity in BRCA1/2 mutant tumor models and better pharmacokinetics profile has the potential to be selected as the clinical candidate for the treatment of treatment of BRCA1/2 deficient cancers.

Anticancer Agent 39 (compound B12), a fluorescent derivative of Jiyuan Oridonin A (JOA), not only induces apoptosis through the collapse of mitochondrial membrane potential (MMP) but also inhibits cell cloning and migration, demonstrating promising anti-proliferative activity against HGC-27 cells with an IC50 value of 0.39 μM [1].

PI3K-IN-47 (Compound 27) is a potent bivalent inhibitor targeting the phosphoinositide 3-kinases (PI3K) family, with IC50 values of 0.44 nM for PI3Kα, and 7.18 nM, 13.92 nM, and 22.83 nM for PI3Kβ, PI3Kγ, and PI3Kδ respectively. It induces G1 phase cell cycle arrest and exhibits anti-neoplastic properties by restraining colony formation and cell migration. Additionally, PI3K-IN-47 has demonstrated the ability to suppress tumor growth in HGC-27 xenograft mouse models [1].

C-02, a proteolysis-targeting chimera (PROTAC) that combines the hexokinase inhibitor lonidamine with the cereblon ligand thalidomide, effectively induces the degradation of hexokinase 2 in 786-O and PANC-1 cells at a concentration of 20 µM. This compound exhibits cytotoxicity to a range of cancer cells, including 786-O, 4T1, PANC-1, HGC-27, and MCF-7, with IC50 values of 34.07 µM, 5.08 µM, 31.53 µM, 6.11 µM, and 21.65 µM, respectively. Additionally, at 20 µM, C-02 diminishes both the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in 4T1 cells, suggesting a suppression of glycolysis and mitochondrial damage. In vivo studies reveal that at a dosage of 50 mg/kg, C-02 not only reduces tumor volume but also promotes intratumoral cytokine accumulation and triggers pyroptosis in a 4T1 murine mammary carcinoma model.