oral bioavailability

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.

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 Cannabidiol-Derived Neuroprotective Agent with Improved Potency, Safety, and Permeability. (EC50=40nM; T1=7500). KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with imp

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].

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.

PF-06291874 (Glucagon receptor antagonists-4) (Glucagon receptor antagonists-4) is a highly effective and orally active antagonist of the glucagon receptor.

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

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.

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) exhibits anticancer properties[1][2]. As a potent and selective PI3Kα inhibitor with high oral bioavailability, it has IC50 values of 5 nM for p110α, 250 nM for p110γ, 290 nM for p110δ, and 1200 nM for p110β, indicating its efficacy in targeting enzymes involved in cancer cell proliferation.

BAY-1316957 is a highly potent and selective EP4 receptor antagonist. With an IC50 of 15.3 nM. Good oral bioavailability[1].

GNF179, an optimized 8,8-dimethyl IP analog, exhibits potency (4.8 nM against the multidrug-resistant strain W2), in vitro metabolic stability, and in vivo oral bioavailability.

Nanatinostat (CHR-3996) is an HDAC inhibitor with selectivity and oral bioavailability, with IC50 values of 3-7 nM for HDAC1 2 3 and >200 nM for other subtypes. Nanatinostat also inhibits tumour cell proliferation and induces apoptosis, for studying neurodegenerative diseases and cancer.

RIPK-IN-4 is an effective and selective inhibitor of RIPK2. It also has excellent oral bioavailability (IC50: 3 nM).

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

RTC-30, an optimized phenothiazine compound, possesses potent anti-cancer properties and is formulated with a hydroxylated linker (N) to enhance its oral bioavailability[1].

MerTK Axl-IN-1 (Compound A-910) is a potent and selective dual inhibitor of MerTK Axl, exhibiting IC50 values of 4.2 nM and 8.8 nM in Ba F3 cells, and 0.2 nM and 0.9 nM in HTRF cells, respectively. It effectively inhibits pMerTK in vivo and possesses a long half-life and high oral bioavailability.

W4275 (Compound 42) is a selective NSD2 inhibitor with oral activity and an IC50 of 17 nM. It exhibits antiproliferative activity, with an IC50 of 230 nM against RS411 cells, and significantly inhibits tumor growth in an RS411 tumor xenograft model. Pharmacokinetic analysis in mice shows that W4275 has a favorable oral bioavailability (F is 27.34%). W4275 holds potential for use in cancer research.