pharmacokinetic

An antibiotic produced by Streptomyces fradiae.

Belzutifan (MK-6482) is a potential treatment for clear cell renal cell carcinoma (ccRCC). Belzutifan is an orally active and selective HIF-2α inhibitor (IC50: 9 nM). Belzutifan , as a second-generation HIF-2α inhibitor, increases potency and improves pharmacokinetic profile.

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

Atabecestat (JNJ-54861911) is a potent, brain-penetrant, and orally active β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor that achieves robust and high CSF Aβ reduction, is well-tolerated, and displays sustained pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. Atabecestat (JNJ-54861911) has the potential for Alzheimer's Disease treatment[1].

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.

CCT365623 is an orally bioavailable Lysyl Oxidase inhibitor with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.

HS271 is a selective, highly potent and orally active IRAK4 inhibitor (IC50= 7.2 μM). HS271 shows excellent enzymatic and cellular activities, as well as excellent pharmacokinetic properties.

Aβ-IN-1 is a novel, potent and orally active γ-secretase modulator (GSM). Aβ-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ-IN-1 shows a sustained pharmacokinetic profile.

ZW4864 (free base) is an orally active and selective β-catenin B-Cell lymphoma 9 protein-protein interaction (β-catenin BCL9 PPI) inhibitor, with a K_i value of 0.76 μM and an IC_50 value of 0.87 μM [1]. ZW4864 (free base) also demonstrates good pharmacokinetic properties.

Fosfomycin calcium (Phosphomycin calcium salt) is a blood-brain barrier penetrating, broad-spectrum antibiotic by irreversibly inhibiting an early stage in cell wall synthesis.

Fosfomycin sodium is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis.

Torin 2(IC50=0.25 nM), a specific and effective mTOR inhibitor, is the 800-fold greater specific activity for mTOR than PI3K and improves pharmacokinetic properties. The EC50 of Torin 2 for ATM ATR DNA-PK inhibition is 28 nM 35 nM 118 nM, respectively.

Aβ42-IN-1, compound 1v, is a novel, potent and orally active γ-secretase modulator (GSM). Aβ42-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ42-IN-1 shows a sustained pharmacokinetic profile.

BPN-15606, an orally active γ-secretase modulator (GSM), significantly reduces Aβ42 and Aβ40 production in SHSY5Y neuroblastoma cells, demonstrating IC50 values of 7 nM and 17 nM, respectively. This compound exhibits favorable pharmacokinetic pharmacodynamic (PK PD) properties, such as bioavailability, half-life, and clearance. Importantly, BPN-15606 markedly decreases Aβ42 and Aβ40 levels in the central nervous system of both rats and mice[1].

HCV-IN-7 is an orally active and potent pan-genotypic HCV NS5A inhibitor (IC50s: 3-47 pM) with a superior pan-genotypic profile, good pharmacokinetic properties, and favorable liver uptake.

HCV-IN-7 hydrochloride is an orally active and potent pan-genotypic HCV NS5A inhibitor [IC50s: 3-47 pM], exhibiting a superior pan-genotypic profile, a good pharmacokinetic profile, and favorable liver uptake.

Mcl-1 inhibitor 3 shows good pharmacokinetic properties and excellent in vivo efficacy without toxicity.Mcl-1 inhibitor 3 is a highly potent and orally activate macrocyclic Mcl-1 inhibitor (Ki= 0.061 nM; IC50=19 nM in an OPM-2 cell viability assay).

(S)-Ceralasertib is a potent and selective inhibitor of sulfoximine morpholinopyrimidine ATR with excellent preclinical physicochemical and pharmacokinetic (PK) characteristics. .

(+)-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.

AMG 837 sodium salt is a potent GPR40 agonist(EC50=13 nM) with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents. IC50 value: 13 nM (EC50) [1] Target: GPR40 agonist AMG 837 displayed the expected t

Autotaxin-IN-1 is a potent autotaxin inhibitor used in the treatment of osteoarthritis pain. It exhibits favorable potency (IC50=2.2 nM), pharmacokinetic (PK) properties, and a robust PK pharmacodynamic (PD) relationship[1].

BAY-707, a highly potent and selective substrate-competitive inhibitor of MTH1 (NUDT1) with an IC50 of 2.3 nM, is well-tolerated in mice and exhibits a favorable pharmacokinetic (PK) profile compared to other MTH1 compounds. However, it demonstrates a clear lack of anticancer efficacy both in vitro and in vivo[1].

BI-1230 is a potent inhibitor of HCV NS3 protease, exhibiting efficacy in the low nanomolar range, and notably suppresses viral replication. This compound demonstrates high selectivity, distinguishing effectively between other serine cysteine proteases. Additionally, BI-1230 exhibits favorable pharmacokinetic (PK) properties[1].

GNF-5 is a specific non-ATP competitive inhibitor of Bcr-Abl (IC50: 0.22±0.1 uM, Wild-type Abl). It is an analog of GNF-2 with improved pharmacokinetic properties.