Pharmacokinetics, Mass Balance, and Biotransformation of [C]tinengotinib, A Novel Multi-target Kinase Inhibitor, in Healthy Subjects.

Background And Objective: Tinengotinib, a novel multi-target small molecule kinase inhibitor, is currently undergoing phase II clinical trial in the USA and China. The purpose of this open-label study was to investigate the absorption, metabolism, and excretion of [C]tinengotinib following a single oral dose in healthy subjects.

Methods: Six healthy male subjects received a single oral dose of [C]tinengotinib capsules at 10 mg/100 µCi, and blood, urine, and feces samples were collected.

The first selective VAP-1 inhibitor in China, TT-01025-CL: safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multiple-ascending doses.

TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers. Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10-300 mg [single dose]; 20-100 mg for 7 days [multiple doses]) or placebo under fasting conditions.

In vitro and in vivo pharmacokinetics, disposition, and drug-drug interaction potential of tinengotinib (TT-00420), a promising investigational drug for treatment of cholangiocarcinoma and other solid tumors.

Early-stage clinical evaluation of tinengotinib (TT-00420) demonstrated encouraging preliminary efficacies in multiple types of refractory cancers, including fibroblast growth factor receptors (FGFR) inhibitors relapsed cholangiocarcinoma (CCA), castrate-resistant prostate cancer (CRPC), and HR+/HER2- breast cancer and triple negative breast cancer (TNBC). To further evaluate drug-like properties of the drug candidate, it is imperative to understand its metabolism and pharmacokinetic properties. This manuscript presented the investigation results of in vitro permeability, plasma protein binding, metabolic stability, metabolite identification, and drug-drug interaction of tinengotinib.

Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous cancer lacking actionable targets. Using a phenotypic screen of TNBC cells, we discovered a novel multiple kinase inhibitor tinengotinib (TT-00420) that strongly inhibited Aurora A/B, FGFR1/2/3, VEGFRs, JAK1/2, and CSF1R in biochemical assays. Exposure to tinengotinib specifically inhibited proliferation across all subtypes of TNBC in vitro and in vivo, while leaving luminal breast cancer cells intact.

Qualitative and quantitative analysis of the major bioactive phenolic compounds of Glechoma longituba by LC-coupled with PAD and ESI-MS detection.

A sensitive and selective method based on HPLC-PAD and Quadrupole TOF ESI-MS-MS is presented for quality control of Glechoma longituba, the major bioactive phenolic compounds of which could be quantified simultaneously. LC-ESI-MS was applied for nine fully identified compounds and another eight partially identified compounds in the plant by comparing their mass spectral data and retention times with those of selected standards and literature data. For quantitative analysis, the chromatographic conditions and extraction procedure were optimized in order to ensure the exhaustive extraction of the plant material.

UPLC-QTOF/MS-based screening and identification of the constituents and their metabolites in rat plasma and urine after oral administration of Glechoma longituba extract.

Glechoma longituba is a widely used traditional Chinese medicine (TCM) in treating various diseases; however, the in vivo integrated metabolism of its multiple bioactive components remains unknown. In this paper, ultra-performance liquid chromatography (UPLC) coupled to quadrupole time-of-flight (QTOF) and the MetaboLynx™ software combined with mass defect filtering (MDF) together provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MS(E) data acquisition. This rapid automated analysis method was successfully applied for screening and identification of the constituents absorbed and metabolized studies of G.

High-performance liquid chromatography--two wavelength detection of triterpenoid acids from the fruits of Ziziphus jujuba containing various cultivars in different regions and classification using chemometric analysis.

A simple and sensitive HPLC-DAD method has been developed for the first time to simultaneously determine 10 triterpenoid acids (ceanothic acid, alphitolic acid, zizyberanal acid, zizyberanalic acid, epiceanothic acid, ceanothenic acid, betulinic acid, oleanolic acid, ursonic acid and zizyberenalic acid) in the dried fruit of Ziziphus jujuba (called Dazao) which has been widely used as one of the traditional Chinese medicines (TCMs). This HPLC assay was performed on a reversed-phase C(18) column (250 mm x 4.6mm, 5 microm) with the column temperature at 35 degrees C.