no cytotoxicity

Flibanserin (Girosa) is a serotonergic antidepressant used to treat hypoactive sexual desire disorder. Flibanserin has been associated with a low rate of minor serum aminotransferase elevations during treatment but has not been linked to instances of clinically apparent acute liver injury.

Tau-aggregation and neuroinflammation-IN-1 is a potent inhibitor of tau protein aggregates, showing significant inhibitory activity against AcPHF6 and full-length tau protein aggregates. It has anti-inflammatory activity, reduces NO release, exhibits low cytotoxicity against LSP-stimulated BV2 cells, and reverses okadaic acid-induced memory impairment in rats.

Compound 27b, also known as hURAT1 inhibitor 1, is an isomarine-derived, orally active inhibitor that targets both hURAT1 and GLUT9 with IC50 values of 0.16 μM and 4.47 μM, respectively. This compound exhibits significant anti-hyperuricemia effects and has demonstrated potent uric acid-lowering activity in a hyperuricemia mouse model at a dose of 10 mg/kg. Importantly, Compound 27b displays no notable in vitro cytotoxicity or in vivo hepatotoxicity, and possesses favorable pharmacokinetic (PK) characteristics.

MC1, an effective NLRP3 inhibitor, exhibits a KD value of 19.3 nM and is devoid of cytotoxicity. This compound enhances cognitive function without causing adverse effects and exhibits no hepatotoxicity. MC1 holds potential for research in Alzheimer's disease.

Antifungalagent 122 (compound 201), a potent and broad-spectrum antifungal agent, prevents the phase shift in fungi and the formation of fungal biofilms. This compound effectively inhibits the enzymatic activity of CYP3A4-M and CYP3A4-T, with IC50 values of 2.11 and 4.53 µM, respectively. Notably, Antifungalagent 122 exhibits no cytotoxicity.

Anticanceragent 263 (compound 7) is an effective anticancer agent. It binds with the G-quadruplex DNA (G4) sequence 22-mer Pu22 (a c-Myc DNA analog). As a structural modulator, Anticanceragent 263 significantly enhances the formation of protein α-helices and has the capacity to form a supramolecular network. Furthermore, Anticanceragent 263 exhibits no cytotoxicity.

PB01 is a DPP-4 inhibitor with an IC50 of 15.66 nM. It effectively suppresses high glucose-induced ROS generation and mitochondrial superoxide production while significantly reducing the cellular expression of DPP-4. Additionally, PB01 notably lowers blood glucose levels in diabetic mice. It demonstrates excellent safety, exhibiting almost no cytotoxicity at a concentration of 100 μM. PB01 holds promise for research in the diabetes field.

α-Glucosidase-IN-79 (Compound 4d9) is a non-competitive α-glucosidase inhibitor with an IC50 of 2.11 μM, demonstrating greater inhibitory potency than the existing α-glucosidase inhibitors Acarbose (IC50 of 327.0 μM) and HXH8r (IC50 of 15.32 μM). It exhibits no cytotoxicity on normal human liver cells (LO2) and shows good metabolic stability in rat plasma. α-Glucosidase-IN-79 holds promise for research in type 2 diabetes.

SLU-10906 (Compound 63) is an orally active inhibitor of Cryptosporidium. It demonstrates activity against the parasite in cell-based infection models with an EC50 of 0.19 μM and exhibits no cytotoxicity. SLU-10906 is a promising candidate for research in cryptosporidiosis.

PPARγ-IN-5 (Compound A3) is an inhibitor of PPARγ. In liver cells, it reduces lipid accumulation and shows no significant cytotoxicity in HepG2 cells at a concentration of 400 µM. PPARγ-IN-5 is applicable for research on non-alcoholic fatty liver disease.

SJPYT-310 is a selective PXR antagonist, exhibiting no noticeable cytotoxicity.

O6BTG-C8-αGlu is an O6-methylguanine-DNA methyltransferase (MGMT) inhibitor with an IC50 of 0.45 μM. At a concentration of 0.1 μM, it fully inhibits MGMT in HeLaS3 cells and demonstrates no cytotoxicity even at prolonged high doses (up to 20 μM). This compound is suitable for research on MGMT-related cancers.

NF-κB/HIF-1α-IN-1 (compound 9c) effectively inhibits the NF-κB activation pathway and demonstrates selective antifibrotic activity. This compound exhibits no significant cytotoxicity in NCI tumor cell lines. In rat models, NF-κB/HIF-1α-IN-1 successfully ameliorates liver fibrosis, suppresses the expression levels of NF-κB and HIF-1α, and induces Nrf2.

AChE-IN-87 is an AChE inhibitor with an IC50 of 0.05 μM and a Ki of 16.93 nM. It exhibits no cytotoxicity toward 3T3 cells and is suitable for Alzheimer's disease (AD) research.

BTK-IN-28 (compound PID-4) is a potent BTK inhibitor with anti-cancer properties. It effectively inhibits BTK and downstream signaling cascades, selectively suppressing the proliferation of Burkitt's lymphoma RAMOS cells, while exhibiting no significant cytotoxicity towards non-tumor cells.

TLR7 agonist18 (Compound 21a) is a selective Toll-like receptor 7 (TLR7) agonist with an EC50 of 7.8 μM. It demonstrates no cytotoxicity in an HEK293 cell line co-transfected with the hTLR7 gene and can induce the secretion of several cytokines, including IL-1β, IL-12p70, IL-8, and TNF-α. This compound is useful in research related to vaccines, asthma, allergies, and cancer treatment.

OX2R-IN-2 (compound 63c) is an agonist of the type 2 orexin receptor (OX2R) with an EC50 value of 339 nM. It can cross the blood-brain barrier and exhibits no cytotoxicity.

IDD-8E is an effective anti-pseudomonal agent (MIC = 4.4 µM) with no cytotoxicity. It demonstrates significant killing of Pseudomonas and disruption of its biofilm. IDD-8E targets the ATP-binding pocket of WaaP and also inhibits other ESKAPE pathogens.

CDK8-IN-19 (Compound 3d) is a CDK8 inhibitor with an IC50 of 25.08 nM. It exhibits broad-spectrum anticancer activity, showing effectiveness against leukemia, melanoma, and breast cancer, while demonstrating no significant cytotoxicity to normal Vero cells (mean IC50 values are 2.87, 3.65, 3.79, and 45.48 μM, respectively).

XL-3158 is an orally active inhibitor of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) with human cGAS IC50 of 11.1 μM and murine cGAS IC50 of 2.19 μM. It binds both allosteric and orthosteric sites, stabilizing the inactive closed conformation of the enzyme, thereby weakening cGAS interaction with DNA. By targeting phase separation, XL-3158 effectively penetrates cells, reduces intracellular cGAS local concentration through inhibition of aggregate formation, and shows no significant cytotoxicity at effective concentrations, making it suitable for subsequent cellular function experiments. XL-3158 overcomes species selectivity barriers, presenting a candidate drug for cGAS-dependent inflammatory diseases.

MXC-017 is an apoptosis inducer capable of crossing the blood-brain barrier, specifically targeting glioma stem cells (GSCs). It effectively prevents the formation of radiation-induced GSCs while promoting G0/G1 cell cycle arrest and apoptosis. With minimal off-target effects, MXC-017 exhibits no significant cytotoxicity even at concentrations up to 10 µM. Additionally, it significantly extends the median survival in patient-derived orthotopic xenograft (PDOX) glioblastoma (GBM) mouse models when used in conjunction with radiation therapy.

PI3Kα-IN-26 (Compound 11e) is a PI3Kα inhibitor with an IC50 of 75.31 nM. It demonstrates broad-spectrum anticancer activity, being effective against leukemia, colon cancer, and breast cancer, while exhibiting no significant cytotoxicity to normal Vero cells (average IC50 values are 2.74, 3.50, 3.34, and 85.29 μM, respectively).

α-Glucosidase-IN-95 (Compound 21c) is a competitive inhibitor of α-Glucosidase, with an IC50 value of 0.44 μM. This compound exhibits significant inhibitory potency and shows no cytotoxicity towards normal cells. α-Glucosidase-IN-95 is applicable for research into metabolic disorders such as diabetes.

SOD1-IN-1 (Compound 9) is a potent SOD1 inhibitor that exhibits no cytotoxicity to cells.