oral bioavailability

GNE-9605 is a highly effective, specifical, and brain-penetrant LRRK2 inhibitor (IC50: 19 nM).

ELN-441958 is a potent, neutral antagonist of the B1 receptor, inhibiting the binding of the B1 agonist ligand [3H]DAKD to IMR-90 cells with a Ki of 0.26 nM. ELN-441958 (ELN 441958) is highly selective for B1 over B2 receptors.

Orforglipron (LY3502970) belongs to non-peptide small molecule GLP-1 receptor agonists and is a highly selective, orally effective GLP-1 receptor agonist with good cell permeability and oral bioavailability. This compound is used in research on type 2 diabetes and obesity, demonstrating significant glucose-lowering and weight-reducing activities.

Bemcentinib (R428) belongs to small molecule inhibitors and is a highly selective oral Axl inhibitor (IC50 = 14 nM) with oral bioavailability and potent cell permeability. This compound effectively inhibits cancer cell migration and invasion, blocks tumor dissemination, and prolongs survival in various tumor models.

Valproic Acid (2-Propylpentanoic Acid) is an HDAC inhibitor that suppresses HDAC1 activity and induces HDAC2 degradation, exhibiting oral bioavailability. Valproic Acid activates Notch1 signalling and inhibits the proliferation of small cell lung carcinoma cells, making it applicable for research into epilepsy and bipolar disorder.

SBP-7455 potently inhibited ULK1/2 enzymatic activity in vitro and in cells, reduced the viability of TNBC cells and had oral bioavailability in mice.

TC ASK 10 is a potent, selective and orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1)(IC50 of 14 nM).

BMS-929075 is an orally active HCV NS5B replicase (HCV NS5B replicase) palm site variant inhibitor with potency, high oral bioavailability and pharmacokinetic parameters.BMS-929075 shows cytotoxicity.

Laniquidar (R101933) is a third generation non-competitive inhibitor of P-glycoprotein (P-gp) (IC50: 0.51 μM) with limited oral bioavailability. It can also be used to modulate multidrug resistance transporters.

PF-07258669 is a small-molecule compound and a melanocortin 4 receptor (MC4R) antagonist (IC50 = 13 nM, Ki = 0.46 nM) with high selectivity, oral bioavailability, and favorable pharmacokinetic properties. This compound can be used for research on diseases such as cachexia and anorexia.

MET kinase-IN-2, a selective and potent MET kinase inhibitor, demonstrates oral bioavailability and exhibits an IC50 value of 7.4 nM. It also possesses antitumor activity[1].

Erythromycin estolate is a semi-synthetic derivative of erythromycin with good oral absorption and bioavailability tolerance. As a macrolide antibiotic, Erythromycin exerts its antibacterial action by inhibiting bacterial protein synthesis and is mainly used in studies for the treatment of respiratory, skin and soft tissue infections caused by susceptible bacteria. Erythromycin estolate may cause liver injury, including mild cholestatic hepatitis, jaundice, and paucity of bile ducts.

Molnupiravir (EIDD-2801) is an isopropyl ester prodrug of the ribonucleoside analog EIDD-1931 with oral bioavailability. Molnupiravir can be used in the study of COVID-19, seasonal and pandemic influenza, and has broad-spectrum antiviral activity against multiple coronaviruses and influenza viruses, such as SARS-CoV-2, MERS-CoV, SARS-CoV.

KLS-13019 is a highly effective and orally active GPR55 receptor antagonist, a cannabidiol (CBD)-derived neuroprotective agent that can reverse chemotherapy-induced peripheral neuropathy (CIPN) and is suitable for studying hepatic encephalopathy (HE).

Bacampicillin is a penicillin antibiotic and a prodrug of ampicillin with good oral bioavailability.

Bacampicillin hydrochloride is an improved oral bioavailability penicillin antibiotic which is a prodrug of ampicillin.

BRD0705 is a potent, orally active GSK3α inhibitor with high selectivity (IC50: 66 nM; Kd: 4.8 μM), demonstrating an 8-fold higher selectivity for GSK3α compared to GSK3β (IC50: 515 nM).

GNF179 Metabolite, the derivative of GNF179—an optimized 8,8-dimethyl IP analog—demonstrates significant potency (4.8 nM against the multidrug-resistant W2 strain) alongside in vitro metabolic stability and in vivo oral bioavailability.

Reutericyclin is a selective anti-Gram-positive substance with good oral bioavailability, possessing both antibacterial and anti-obesity effects. It disrupts bacterial transmembrane potential specifically, exerting bactericidal or bacteriostatic effects on pathogenic bacteria such as Clostridium difficile and Staphylococcus aureus in a non-bacteriolytic manner, and rapidly eliminates vegetative cells and spores of Clostridium difficile. It is resistant to enzymatic degradation, has iron chelating properties, and is hardly absorbed by colonic epithelial cells. In addition to effectively eliminating Staphylococcus biofilms and inhibiting the proliferation of drug-resistant bacteria, Reutericyclin regulates intestinal flora structure and improves body energy metabolism, thereby alleviating abnormal weight gain induced by risperidone medication. Currently, Reutericyclin has been widely used in basic research on Clostridium difficile infection, drug-induced weight gain and superficial skin infection caused by Staphylococcus.

SDZ 220-581 hydrochloride is a highly potent competitive NMDA receptor antagonist with good oral bioavailability and a pKᵢ of 7.7.

Cevimeline hydrochloride hemihydrate ((-)-SNI-2011), a novel muscarinic receptor agonist, is being explored as a potential treatment for xerostomia in Sjogren's syndrome, exhibiting an IC50 value indicative of its affinity for mAChR. This compound's pharmacological effects on the gastrointestinal, urinary, and reproductive systems, alongside its impact on various tissues, were thoroughly examined in species including mice, rats, guinea pigs, rabbits, and dogs. The metabolic breakdown of (-)-SNI-2011 was studied in vitro using rat and dog liver microsomes to assess its biotransformation. Upon oral administration, peak plasma concentrations were reached within an hour in both rats and dogs, showcasing rapid absorption and a subsequent decrease in concentration with a half-life ranging from 0.4 to 1.1 hours. Bioavailability was noted at 50% in rats and 30% in dogs. Metabolic pathways highlighted significant species differences, with both S- and N-oxidized metabolites identified in rats, but only N-oxidized metabolites in dogs. Additionally, gender differences in pharmacokinetics were observed in rats but were absent in dogs. In vitro studies pinpointed the involvement of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in the metabolism of (-)-SNI-2011, specifically through sulfoxidation and N-oxidation processes, respectively. CYP2D and CYP3A were identified as the primary enzymes responsible for sulfoxidation in rat liver microsomes.

(+)-Cevimeline hydrochloride hemihydrate ((+)-SNI-2011), a potent muscarinic receptor agonist, shows promise as a therapeutic candidate for xerostomia in Sjogren's syndrome. It exhibits a broad pharmacological profile across various systems in animal models including mice, rats, guinea pigs, rabbits, and dogs. Metabolism studies using rat and dog liver microsomes reveal rapid absorption with peak plasma concentrations (Cmax) within one hour post-oral administration and a half-life (t1/2) between 0.4 to 1.1 hours. Bioavailability is 50% in rats and 30% in dogs. Metabolic analysis shows species-specific differences: rats produce S- and N-oxidized metabolites, while dogs produce only N-oxidized metabolites. Sex-based pharmacokinetic differences were noted in rats but not in dogs. In vitro studies indicate cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) involvement in the sulfoxidation and N-oxidation of SNI-2011, with CYP2D and CYP3A mainly responsible for sulfoxidation in rat liver microsomes.

Alpelisib hydrochloride (BYL-719 hydrochloride) is a potent PI3Kα inhibitor (IC₅₀ = 5 nM) with selectivity and oral bioavailability, exhibiting activity against PI3Kβ/γ/δ that is dozens of times weaker than against PI3Kα (IC₅₀ = 250/290/1200 nM). Alpelisib exhibits targeting activity against PIK3CA-mutated tumors and may be utilized in cancer research.

ar-Turmerone is a natural volatile organic compound extracted from the rhizomes of turmeric (Curcuma longa). ar-Turmerone exhibits oral bioavailability and possesses biological activities such as antitumor, anti-inflammatory, antioxidant, and neuroprotective effects. ar-Turmerone exerts a positive regulatory effect on dendritic cells in mice. Ar-turmerone can induce neural stem cell proliferation both in vitro and in vivo, making it useful for research on neurological disorders. Ar-turmerone induces apoptosis in U937 cells.