A5085929266- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
- Statistical Methods in Clinical Trials
- Biosimilars and Bioanalytical Methods
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- Peptidase Inhibition and Analysis
- Drug-Induced Hepatotoxicity and Protection
- Cancer therapeutics and mechanisms
- Pharmacogenetics and Drug Metabolism
- Microtubule and mitosis dynamics
- Protein purification and stability
- Drug Transport and Resistance Mechanisms
- Cutaneous lymphoproliferative disorders research
- Metabolism and Genetic Disorders
- Mathematical Biology Tumor Growth
- Multiple Myeloma Research and Treatments
- Neuroendocrine Tumor Research Advances
Weatherford College
2023
Xiamen University Malaysia
2023
Zhejiang Normal University
2022
Phillips Academy
2022
IQ Samhällsbyggnad
2021
La Roche College
2020
Dalian Maritime University
2018-2020
University of Florida
2020
Columbus Oncology and Hematology Associates
2020
Xinjiang University
2019
Inhibition of kinesin spindle protein (KSP) is a novel mechanism for treatment cancer with the potential to overcome limitations associated currently employed cytotoxic agents. Herein, we describe C2-hydroxymethyl dihydropyrrole KSP inhibitor (11) that circumvents hERG channel binding and poor in vivo potency, issues limited earlier compounds from our program. However, introduction group caused 11 be substrate cellular efflux by P-glycoprotein (Pgp). Utilizing knowledge garnered previous...
To characterize the population pharmacokinetics (PKs) of subcutaneous (SC) and intravenous (IV) trastuzumab in early breast cancer (EBC), assess impact covariates on PK, evaluate fixed (nonweight-based) dosing for SC regimen administrated via handheld syringe. Serum concentrations from 595 patients with HER2-positive EBC HannaH study (fixed 600 mg or weight-based IV trastuzumab) were analyzed using nonlinear mixed-effects modeling. Multiple logistic regression was used to exposure–response...
Abstract Mosunetuzumab (Mosun) is a CD20xCD3 T‐cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step‐up dose regimen of 1/2/60/30 mg IV designed mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed/refractory B‐Cell Non‐Hodgkin lymphoma receiving Mosun monotherapy, including fixed dosing (0.05–2.8 every 3 weeks (q3w)) Cycle 1...
Abstract Silent Night : Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for treatment insomnia. Herein, we describe discovery dual (OX 1 R/OX 2 R) receptor antagonist featuring 1,4‐diazepane central constraint that blocks signaling in vivo. In telemetry‐implanted rats, oral administration this produced decrease wakefulness, while increasing REM and non‐REM sleep. magnified image
PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively pursued to treat a variety of cancers in oncology. To search for structurally differentiated back-up candidate PF-04691502, which is currently phase I/II clinical trials treating solid tumors, lead optimization effort was carried out with tricyclic imidazo[1,5]naphthyridine series. Integration structure-based drug design physical properties-based yielded potent selective PI3K/mTOR dual kinase inhibitor...
Autonomous ships or Unmanned Surface Vehicles (USV) collision avoidance and path planning problems among multi-vessels are investigated in this paper. Firstly, a modified fuzzy dynamic risk of model based on time space index is proposed, which much closer to real ship applications. Then, the fitness functions collision, navigational economy, International Regulations for Preventing Collisions at Sea 1972 (COLREGs) timing established respectively ensure rationality decisions. Moreover, with...
Purpose: Model-based tumor growth inhibition (TGI) metrics are increasingly incorporated into go/no-go decisions in early clinical studies. To apply this methodology to new investigational combinations requires independent evaluation of TGI recently completed Phase III trials effective immunotherapy. Patients and Methods: Data were extracted from IMpower150, a positive, randomized, study first-line therapy 1,202 patients with non–small cell lung cancer. We resampled baseline characteristics...
Giredestrant(GIR), an oral selective estrogen receptor antagonist and/ degrader(SERD), was studied in Phase Ia/b GO39932 study(NCT03332797). GIR administered alone or with palbociclib(palbo) to patients ER-positive, HER2-negative, locally advanced metastatic breast cancer who had disease progression on prior endocrine therapies. In the single-agent dose-escalation stage, received 10, 30, 90, 250 mg of once-daily(QD) GIR. dose-expansion 100, QD Safety and tolerability 100 GIR+125 palbo also...
Diclofenac, a nonsteroidal anti-inflammatory drug, is metabolized to diclofenac-1-O-acyl glucuronide (D-1-O-G), chemically reactive conjugate that has been implicated as playing role in the idiosyncratic hepatoxicity associated with its use. The present studies investigated ability of diclofenac be diclofenac-S-acyl-glutathione thioester (D-SG) vitro incubations rat and human hepatocytes whether formation dependent on transacylation-type reaction between D-1-O-G glutathione. When (100 μM)...
The recently introduced Clonetics human corneal epithelium (cHCE) cell line is considered a promising in vitro permeability model, replacing excised animal cornea to predict of topically administered compounds. purpose this study was further characterize cHCE as model from both drug metabolism and transport aspects. First, good correlation found the values (P(app)) obtained rabbit corneas for various ophthalmic drugs markers. Second, previously established real-time quantitative polymerase...
vc-MMAE antibody–drug conjugates (ADCs) consist of a monoclonal antibody (mAb) covalently bound with potent anti-mitotic toxin (MMAE) through protease-labile valine-citrulline (vc) linker. The objective this study was to characterize the pharmacokinetics (PK) and explore exposure–response relationships eight ADCs, against different targets for diverse tumor indications, using data from first-in-human Phase 1 studies. PK parameters three analytes, namely antibody-conjugated MMAE (acMMAE),...
Chemically reactive species formed from the metabolism of carboxylic acid-containing compounds have been proposed as mediators their toxic side-effects. Two alternative metabolic pathways known to be involved in generation acylating metabolites acids are acyl glucuronidation and acyl-CoA formation. Here, we present studies with 2-phenylpropionic acid focused on evaluating relative abilities glucuronides versus derivatives transacylate nucleophilic cysteinyl-thiol glutathione. Thus, synthetic...
Abstract Purpose: Targeting CD79B using antibody–drug conjugates (ADC) is an effective therapeutic strategy in B-cell non-Hodgkin lymphoma (B-NHL). We investigated DCDS0780A, anti-CD79B ADC with THIOMAB technology (TDC) that consistently two anti-neoplastic molecules per antibody, contrast ADCs heterogeneous loads. Patients and Methods: This phase 1 study enrolled 60 patients histologically confirmed B-NHL had relapsed/failed to respond following ≥1 prior treatment regimens; 41 (68%) diffuse...
Abstract Mosunetuzumab is a CD3/CD20 bispecific antibody. As an on‐target effect, transient elevation of interleukin‐6 (IL‐6) occurs in early treatment cycles. A physiologically‐based pharmacokinetic (PBPK) model was developed to assess potential drug interaction caused by IL‐6 enzyme suppression on cytochrome P450 3A (CYP3A) during mosunetuzumab treatment. The model's performance predicting CYP3A and subsequent drug–drug interactions (DDIs) verified using existing clinical data DDIs chronic...
Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab in combination with rituximab, cyclophosphamide, doxorubicin, prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using previously developed popPK model,...