A5059602286- Cancer Mechanisms and Therapy
- Synthesis and biological activity
- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Melanoma and MAPK Pathways
- Pancreatic and Hepatic Oncology Research
- Fibroblast Growth Factor Research
- Colorectal Cancer Treatments and Studies
- Kruppel-like factors research
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Cutaneous Melanoma Detection and Management
- Cancer Genomics and Diagnostics
- Metastasis and carcinoma case studies
- Cytokine Signaling Pathways and Interactions
- Protein Degradation and Inhibitors
- Phosphodiesterase function and regulation
- Assisted Reproductive Technology and Twin Pregnancy
- Protein Kinase Regulation and GTPase Signaling
- Diabetes Treatment and Management
Jnana Therapeutics (United States)
2024
GlaxoSmithKline (United States)
2012-2020
Bioscience (China)
2020
Entasis Therapeutics (United States)
2020
Boehringer Ingelheim (United States)
2009-2016
GlaxoSmithKline (France)
2014
Sun Yat-sen University
2014
Mackay Memorial Hospital
2011
Taipei City Hospital
2011
Boehringer Ingelheim (Germany)
2010
Activating mutations in serine–threonine protein kinase B-RAF (BRAF) are found 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared chemotherapy, but responses often short-lived. In previous trials, MEK inhibition appeared to be promising this population.
Background Activating mutations in serine–threonine protein kinase B-RAF (BRAF) are found 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared chemotherapy, but responses often short-lived. In previous trials, MEK inhibition appeared to be promising this population. Methods In phase 3 open-label trial, we randomly assigned 322 who had metastatic melanoma a V600E or V600K BRAF mutation receive either trametinib, an oral selective...
Serum anti-Müllerian hormone (AMH) had been proposed as a marker of ovarian reserve. The aim this study was to evaluate the impact endometrioma and laparoscopic cystectomy on reserve measured by serum AMH levels.A total 1,642 patients were recruited in retrospective analysis. Control group (group 1) included 1,323 infertility without endometrioma. Endometrioma 2) 141 with Previous 3) 147 who underwent unilateral or bilateral due more than 6 months before enrollment. Current 4) 31 during...
Abstract Purpose This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial receptors, Aurora A/B, in patients with advanced solid tumors. Patients Methods received orally daily 28-day cycles. Dose escalation was guided by Bayesian modeling using overdose control. The primary objective to assess...
There is an urgent need to develop new targeted treatment agents for small cell lung cancer (SCLC). Tinengotinib (TT-00420) a novel, multi-targeted, and spectrally selective small-molecule kinase inhibitor that has shown significant inhibitory effects on certain solid tumors in preclinical studies. However, its role mechanism of action SCLC remain unclear. In this study, we demonstrated tinengotinib effectively inhibited proliferation, especially highly expressing NeuroD1 (SCLC-N), the...
Abstract Histone deacetylase inhibitors represent a promising new class of anticancer agents. In the current investigation, we examined activity PXD101, potent histone inhibitor, used alone or in combination with clinically relevant chemotherapeutics (docetaxel, paclitaxel, and carboplatin), preclinical vitro vivo models ovarian cancer. was cancer multidrug-resistant cell lines grown monolayer culture, primary clinical specimens three-dimensional organoid culture. PXD101 found to inhibit...
Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases responsible for a large proportion of the phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with antibiotics negate action β-lactamases, thereby restoring activity β-lactam. Newly developed BLIs offer some advantage over older terms enzymatic spectrum but limited...
Diminished ovarian reserve (DOR) remains one of the greatest obstacles affecting chance a successful live birth after fertility treatment. The present study was set to investigate whether using "dual trigger" consisted human chorionic gonadotropin (hCG) plus releasing hormone agonist (GnRH-a) for final oocyte maturation could improve IVF cycle outcomes patients with diminished reserve. A total 427 completed GnRH-antagonist downregulated cycles fresh embryo transfer (ET) were included in this...
434 Background: Tinengotinib is a spectrum-selective multi-kinase inhibitor with unique binding properties to FGFR, potently inhibited FGFR2 fusion/rearrangement and acquired resistant mutations in pre-clinical models phase I trials that included cholangiocarcinoma (CCA) patients (pts). Here we present the efficacy safety of tinengotinib II clinical trial. Methods: Eligible pts advanced/metastatic CCA who had received ≥ 1 prior systemic chemotherapy therapy ECOG PS 0 or were treated 10 mg...
Human FIZZ3 (hFIZZ3) was identified as an ortholog of mouse resistin (mResistin), adipocyte-specific secreted factor linked to insulin resistance in rodents. Unlike mResistin, hFIZZ3 is expressed macrophages and monocytes, but undetectable adipose tissue. The profound macrophage infiltration that occurs during obesity suggests may play important role adipocyte biology. Using a recombinant protein produced Escherichia coli, we report here chronic treatment cultured human adipocytes with...
We report our discovery of a novel series potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Starting from lead identified by scaffold-hopping approach, development efforts were focused on exploring structure-activity relationships, optimizing pharmacokinetic profile, improving in vitro vivo efficacy, evaluating safety profile. The selected candidate, Imigliptin, is now undergoing clinical trial.
608 Background: Tinengotinib, a spectrum-selective multi-kinase inhibitor with unique binding properties to FGFR , potently inhibited FGFR2 fusion/rearrangement and acquired resistant/gatekeeper mutations in pre-clinical models exhibited antitumor activity cholangiocarcinoma (CCA) patients (pts) phase 1/2 trials. Here we present the overall survival (OS) data biomarker correlative analysis from 2 clinical trial of tinengotinib CCA. Methods: Eligible pts advanced/metastatic CCA who had...
Triple-negative breast cancer (TNBC) is a highly heterogeneous lacking actionable targets. Using phenotypic screen of TNBC cells, we discovered 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 specifically proliferation across all subtypes vitro vivo, while leaving luminal cells intact. Incubation HCC1806 with led dose-dependent downregulation genes essential for cell growth...
3019 Background: Tinengotinib is a spectrum-selective multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus (JAK), receptor tyrosine (FGFRs, VEGFRs). has shown preliminary efficacy in prostate cancer (PC), hormone positive (HR+)/human epidermal growth factor 2 negative (HER2-) breast (BC), triple-negative BC (TNBC) cholangiocarcinoma (CCA) Phase (Ph) 1 trial. Here we present the safety, pharmacokinetics...
LBA8509 The full, final text of this abstract will be available at abstract.asco.org 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to 20, issue Journal Clinical Oncology. Onsite Meeting, printed Monday edition ASCO Daily News.
8029 Background: KRAS mutations are detected in 25% of NSCLC, and there no approved targeted therapies for this subset NSCLC. D, an second-line treatment has a response rate < 10%. T is reversible, highly selective allosteric inhibitor MEK1/2 activation kinase activity. This phase II trial (NCT01362296) evaluated the efficacy vs D pts with advanced KRAS-mutant NSCLC who had received prior platinum-based chemotherapy. Methods: Pts were randomized 2:1 to (2 mg QD) or (75 mg/m 2 IV every 3...