A5021773274- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Multiple Myeloma Research and Treatments
- Lung Cancer Treatments and Mutations
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Lung Cancer Research Studies
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Mechanisms and Therapy
- Colorectal Cancer Treatments and Studies
- Click Chemistry and Applications
- Gastrointestinal Tumor Research and Treatment
- Peptidase Inhibition and Analysis
- Lymphoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- HER2/EGFR in Cancer Research
Pharmaxis (Australia)
2023-2024
Vifor Pharma (United States)
2024
Flow Pharma (United States)
2024
Flinders Medical Centre
2024
Sun Yat-sen University
2023-2024
Sun Yat-sen University Cancer Center
2023-2024
Guangxi University
2023
Chinese Academy of Medical Sciences & Peking Union Medical College
2018-2023
Taixing People's Hospital
2022
Guilin University of Technology
2019-2020
We previously reported the design of spirooxindoles with two identical substituents at carbon-2 pyrrolidine core as potent MDM2 inhibitors. In this paper we describe an extensive structure–activity relationship study class inhibitors, which led to discovery 60 (AA-115/APG-115). Compound has a very high affinity (Ki < 1 nM), cellular activity, and excellent oral pharmacokinetic profile. is capable achieving complete long-lasting tumor regression in vivo currently phase I clinical trials for...
Abstract LIGHT is a recently identified member of the TNF superfamily and its receptors, herpesvirus entry mediator lymphotoxin β receptor, are found in T cells stromal cells. In this study, we demonstrate that selectively expressed on immature dendritic (DCs) generated from human PBMCs. contrast, not detectable DCs either freshly isolated PBMCs or rendered mature vitro by LPS treatment. Blockade soluble receptor-Ig HVEM-Ig, inhibits induction DC-mediated primary allogeneic cell response....
TR6 (decoy receptor 3 (DcR3)) is a new member of the tumor necrosis factor (TNFR) family. mRNA expressed in lung tissues and colon adenocarcinoma, SW480. In addition, expression was shown endothelial cell line induced by phorbol 12-myristate 13-acetate/ionomycin Jurkat T leukemia cells. The open reading frame encodes 300 amino acids with 29-residue signal sequence but no transmembrane region. Using histidine-tagged recombinant TR6, we screened soluble forms TNF-ligand proteins...
By using the amino acid sequence motif of tumor necrosis factor (TNF), we searched expressed tag data base and identified a novel full-length cDNA encoding 285 residues named it THANK. THANK is type II transmembrane protein with 15–20% overall homology to TNF, LT-α, FasL, LIGHT, all members TNF family. The mRNA for was at high levels by peripheral blood leukocytes, lymph node, spleen, thymus low small intestine, pancreas, placenta, lungs. also prominently in hematopoietic cell lines....
Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilitiesfor development immunization strategies for patients with metastatic melanoma. With use recombinant adenoviruses expressing either gp100 to immunize melanoma, we evaluated safety, immunologic, and potential therapeutic aspects these immunizations. Methods: In phase I studies, 54 received escalating doses (between 10 7 11 plaque-forming units)...
<h3>Background</h3> Programmed death-1 (PD-1) immune checkpoint blockade has achieved clinical successes in cancer therapy. However, the response rate of anti-PD-1 agents remains low. Additionally, a subpopulation patients developed hyperprogressive disease upon PD-1 Combination therapy with targeted may improve immunotherapy. Recent studies show that p53 activation myeloid linage suppresses alternative (M2) macrophage polarization, and attenuates tumor development invasion, leading to...
Abstract Background BCR-ABL1 T315I mutations confer resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Olverembatinib is a new potent TKI with preclinical activity against T315I-mutated CML. In phase 1/2 studies, we explored the safety and efficacy of olverembatinib Chinese adults TKI-resistant CML (CML-CP) accelerated (CML-AP). Methods 1 study, was orally administered once every other day 28-day cycles at 11 dose cohorts ranging from 60 mg, evaluated maximum...
A novel member of the tumor necrosis factor (TNF) family has been identified from human umbilical vein endothelial cell cDNA library, named vascular growth inhibitor (VEGI). The VEGI gene was mapped to chromosome 9q32. for encodes a protein 174 amino acid residues with characteristics type II transmembrane protein. Its sequence is 20-30% identical other members TNF family. Unlike family, expressed predominantly in cells. Local production secreted form via transfer caused complete suppression...
Abstract Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous clonal disease associated with unmet medical needs. Paralleling the pathology of other cancers, AML tumorigenesis propagation can be ascribed to dysregulated cellular processes, including apoptosis. This function others are regulated by tumor suppressor P53, which plays pivotal role in leukemogenesis. Opposing P53-mediated activities mouse double minute 2 homolog (MDM2), promotes P53 degradation. Because TP53...
Development of B-cell lymphoma 2 (BCL-2)-specific inhibitors poses unique challenges in drug design because BCL-2 homology domain 3 (BH3) shared between family members and the shallow surface their protein-protein interactions. We report herein discovery extensive preclinical investigation lisaftoclax (APG-2575).Computational modeling was used to "lead" compounds. Biochemical binding, mitochondrial BH3 profiling, cell-based viability or apoptosis assays were determine selectivity potency...
Abstract We searched the expressed sequence tag database using homology and identified a novel cytokine, which we have named TRANK (thioredoxin peroxidase-related activator of NF-κB c-Jun N-terminal kinase). The predicted amino acid was highly homologous to that thiol-specific antioxidant proteins. Unlike these proteins, however, had putative secretory signal polypeptide found be secreted by cells. in most tissues cell lines, gene encodes it mapped chromosome Xp21–22.1. activated induced...
Zhai, Yifan; Yang, James C.; Spiess, Paul; Nishimura, Michael I.; Overwijk, Willem W.; Roberts, Bruce; Restifo, Nicholas P.; Rosenberg, Steven A. Author Information
Gastric cancer is the leading cause of related death worldwide. Radiation alone or combined with chemotherapy plays important role in locally advanced and metastatic gastric adenocarcinoma. MDM2–p53 interaction downstream signaling affect cellular response to DNA damage which leads cell cycle arrest apoptosis. Therefore, restoring p53 function by inhibiting its MDM2 a promising therapeutic strategy for cancer. APG-115 novel small molecule inhibitor blocks p53. In this study, we investigated...
Abstract Background Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents potential vulnerability exploitable by senolytic agents. Methods We established new patient-derived PA cell lines that preserve molecular features primary tumors can be studied in...
Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations anaplastic lymphoma (ALK), ROS proto-oncogene 1 receptor tyrosine (ROS1), and focal adhesion (FAK). Here present the preclinical evaluation APG-2449, which exhibits antiproliferative activity in cells...
11502 Background: SDH-deficient GIST is a rare type of GIST, mainly observed in the stomach children and adolescents or young adults < 30 years age. No active targeted therapies have been identified this subset GIST. Olverembatinib, approved China for treatment patients with chronic myeloid leukemia, has shown promising clinical efficacy We report here updated data preliminary paraganglioma, which an SDH-deficient–related tumor. Methods: The aim study was to evaluate safety (per RECIST...
Abstract Purpose: This global phase I trial investigated the safety, efficacy, pharmacokinetics, and pharmacodynamics of lisaftoclax (APG-2575), a novel, orally active, potent selective B-cell lymphoma 2 (BCL-2) inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia small (R/R CLL/SLL) other hematologic malignancies (HMs). Patients Methods: Maximum tolerated dose (MTD) recommended II were evaluated. Outcome measures safety tolerability (primary) pharmacokinetic...
Recently, we reported a novel protein of the tumor necrosis factor (TNF) superfamily, named vascular endothelial cell growth inhibitor (VEGI), which is expressed predominantly in cells. When secreted form this new was overexpressed mouse colon cancer cells, tumors formed by these cells black mice inhibited. We now report that recombinant VEGI inhibits proliferation but not other types examined. The also formation capillary-like structures collagen gels, and capillaries into gels placed on...
Abstract Purpose: B-cell lymphoma-extra-large (BCL-xL) regulates apoptosis and is an attractive anticancer therapeutic target. However, BCL-xL inhibition also kills mature platelets, hampering clinical development. Using innovative prodrug strategy, we have developed pelcitoclax (APG-1252), a potent, dual BCL-2 inhibitor. Aims of this study were to characterize the antitumor activity safety explore its underlying mechanisms action (MOA). Patients Methods: Cell line–derived xenograft...
3126 Background: APG-115 is a potent and orally active small-molecule MDM2 protein inhibitor. Binding to protein, restores p53 tumor suppressive function via induction of apoptosis in cells retaining wild-type p53. In addition, enhanced antitumor activity was demonstrated the syngeneic models after combined with PD-1 blockade. Methods: This Phase I study (APG-115-US-001) designed enroll patients advanced solid tumors US (NCT02935907). Study objectives included assess safety, dose limited...