A5072215414- Melanoma and MAPK Pathways
- Galectins and Cancer Biology
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Colorectal Cancer Treatments and Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cutaneous Melanoma Detection and Management
- Plant-derived Lignans Synthesis and Bioactivity
- Phytochemistry and Biological Activities
- Sphingolipid Metabolism and Signaling
- Chronic Myeloid Leukemia Treatments
- Platelet Disorders and Treatments
- Diabetes Treatment and Management
- Synthesis of Tetrazole Derivatives
- Macrophage Migration Inhibitory Factor
- HER2/EGFR in Cancer Research
- Helicobacter pylori-related gastroenterology studies
- Acute Myeloid Leukemia Research
- Toxin Mechanisms and Immunotoxins
- Cancer Mechanisms and Therapy
- Glycosylation and Glycoproteins Research
- Pancreatitis Pathology and Treatment
- Plant Toxicity and Pharmacological Properties
- Blood groups and transfusion
- Neutropenia and Cancer Infections
Galecto (Denmark)
2021-2024
Novartis (Switzerland)
2015-2019
Novartis Institutes for BioMedical Research
2019
Pierre Fabre (France)
2006
Abstract Purpose: Encorafenib, a selective BRAF inhibitor (BRAFi), has pharmacologic profile that is distinct from of other clinically active BRAFis. We evaluated encorafenib in phase I study patients with BRAFi treatment-naïve and pretreated BRAF-mutant melanoma. Experimental Design: The activity was first characterized preclinically. Encorafenib monotherapy then tested across range once-daily (50–700 mg) or twice-daily (75–150 regimens I, open-label, dose-escalation -expansion adult...
Abstract Purpose Galectin-3, a β-galactoside-binding lectin, plays key role in several cellular pathways involved chronic inflammation, heart disease and cancer. GB1211 is an orally bioavailable galectin-3 inhibitor, developed to be systemically active. We report safety pharmacokinetics (PK) of healthy participants. Methods This phase 1, double-blind, placebo-controlled, first-in-human study (NCT03809052) included single ascending-dose (with food-effect cohort) where participants across...
High circulating galectin-3 is associated with poor outcomes in patients coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside inhibitor antiinflammatory and antifibrotic actions, would be safely effectively delivered COVID-19 pneumonitis.
To evaluate the single agent activity, pharmacokinetics and tolerability of novel tubulin targeted vinflunine (VFL) (320 mg m−2 q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment subsequently first-line A/T combination for advanced/metastatic disease; or relapsed >6 months completion therapy were treated alternative...
Abstract Ruxolitinib is mainly metabolized by cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C9 followed minor contributions of other hepatic CYP in vitro . A physiologically based pharmacokinetic (PBPK) model was established to evaluate the changes ruxolitinib systemic exposures with co-administration perpetrators. The fractions liver via oxidation (fm,CYP3A4 = 0.75, fm,CYP2C9 0.19, fm,CYPothers 0.06) for an initial on data were optimized (0.43, 0.56, 0.01, respectively) using observed...
To assess the pharmacokinetics (PK), safety, and tolerability of siponimod major metabolites in subjects with mild, moderate, severe hepatic impairment (HI) compared demographically-matched healthy (HS).This open-label, parallel-group study enrolled 40 (each HI group, n = 8; HS 16). A staged design was employed starting enrollment mild HI, followed by those moderate HI. All received single oral doses 0.25 mg on day 1; PK safety data were collected during 21-day follow-up.All had similar...
Our objective was to support initial eltrombopag doses and dose titration based on modeling simulation of plasma exposure platelet count response in pediatric patients aged 1–17 years with previously treated chronic immune thrombocytopenia enrolled two clinical studies. Data from 168 were used develop a life‐span population pharmacokinetic pharmacodynamic model including three four compartments enabling counts for various starting schedules. This work supported 50 mg once daily (q.d.)...
Topic: 16. Myeloproliferative neoplasms - Clinical Background: Myelofibrosis (MF) treatment (Tx) with Janus kinase (JAK) inhibitors is limited by modest effects on bone marrow (BM) fibrosis & driver mutation allele burden. A high proportion of patients (pts) discontinue Tx due to cytopenias. GB2064, a LOXL2 inhibitor, being developed as potential disease-modifying for MF. Aims: To evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) clinical effects, specifically BM...
Abstract Rationale High galectin-3 levels predict poor outcomes in patients with COVID-19. Galectin-3 activates monocytes and macrophages which are directly implicated COVID-19 immunopathology the cytokine storm. GB0139 is a potent thiodigalactoside inhibitor may reduce severe effects of disease. We report safety pharmacokinetics pharmacodynamics inhaled inhibitor, GB0139, assess clinical key systemic inflammatory biomarkers hospitalised (ClinicalTrials.gov/EudraCT identifier: NCT04473053...
TPS9152 Background: Gal-3 is a protein that binds specifically to N-acetylglucosamine-expressing carbohydrates, which are upregulated on key tumorigenic cell surface proteins. widely over-expressed in the tumor microenvironment and generally linked poor outcomes. regulates immune function of T cells macrophages, promotes neovascularization fibrosis [Peng Cancer Res 2008; Markowska J Biol Chem 2011; Kouo Immunol 2015]. sequesters interferon gamma, reduces T-cell influx, contributes evasion...
Availability of well-tolerated novel agents that can slow or stop disease progression and improve quality life remain an unmet medical need in IPF management. GB0139, a inhaled galectin-3 inhibitor, has shown good tolerability antifibrotic potential via changes biomarkers associated with animal model (Delaine, T. et al. Chembiochem 2016;17:1759–70) Phase I study (Hirani, N. Eur Respir J 2021;57(5):2002559) healthy participants patients. We report the design IIb GB0139 IPF. This randomised,...
OBJECTIVE:To assess the pharmacokinetics (PK), safety and tolerability of siponimod major metabolites in subjects with mild, moderate severe hepatic impairment (HI) versus healthy (HS). BACKGROUND:Following oral administration, is mainly eliminated by metabolism biliary excretion. Alterations excretory/metabolic activities due to HI can lead drug/metabolite accumulation an extent that may require dosage adjustment. METHODS:This was open-label, parallel-group study, 8 each moderate,...
OBJECTIVE: To assess if the placebo-corrected, baseline-adjusted mean QTcF (ΔΔQTcF) effect of therapeutic (2mg) and supratherapeutic (10mg) doses siponimod (BAF312) exceeds regulatory threshold level concern, defined as 5ms, evidenced by upper bound two-sided 90% CI for largest QTc 10ms. BACKGROUND: Siponimod is a next generation selective sphingosine 1-phosphate -1 -5 receptor modulator, currently in Phase 3 development treatment secondary progressive multiple sclerosis. This TQT study...
<p>Summary of pharmacokinetic parameters (cycle 1 day [C1D1] and cycle 15 [C1D15]) by treatment group in the dose-escalation phase (QD regimen)</p>
<p>Biochemical and cellular potency of encorafenib, dabrafenib, vemurafenib in biochemical cell-based assays. Purified BRAF V600E kinase domain was used the experiments, using kinase-dead MEK1 as a substrate phosphorylated (Ser217/221) alpha-screen readout. A375 cells were incubated with inhibitors for 3 hours to determine ERK (pERK) half maximal effective concentration (EC50) 72 proliferation EC50</p>
<p>Best percentage change in sum of longest diameters target lesion from baseline, by patient, treatment group, and mutation status, patients with BRAFi-naive (A) pretreated (B) melanoma. Grouped analysis the dose-escalation -expansion phases.</p>
<p>Proliferation half maximal inhibitory concentration (IC50) of encorafenib, dabrafenib, and vemurafenib against a panel BRAF V600-mutant melanoma colorectal cell lines. Red squares represent V600E-mutant, blue V600D/K-mutant lines</p>