A5084386900- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Histone Deacetylase Inhibitors Research
- Multiple Myeloma Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Neuroendocrine Tumor Research Advances
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Fibroblast Growth Factor Research
- PI3K/AKT/mTOR signaling in cancer
- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- Lung Cancer Treatments and Mutations
- Viral-associated cancers and disorders
- Cancer-related gene regulation
- Urticaria and Related Conditions
- Immune Cell Function and Interaction
- Cancer Treatment and Pharmacology
- Carbohydrate Chemistry and Synthesis
- Immune cells in cancer
Incyte (United States)
2016-2025
First Affiliated Hospital of Zhengzhou University
2025
State Key Laboratory of Chemical Engineering
2025
Qingdao University of Science and Technology
2025
Sichuan University
2013-2023
West China Hospital of Sichuan University
2013-2023
University of Cambridge
2018-2021
Cambridge School
2021
Jiangsu Hengrui Medicine (China)
2021
Akebia Therapeutics (United States)
2020
OBJECTIVE 11-β-hydroxysteroid dehydrogenase type 1 (11βHSD1) converts inactive cortisone into active cortisol, thereby amplifying intracellular glucocorticoid action. The efficacy and safety of the 11βHSD1 inhibitor INCB13739 were assessed when added to ongoing metformin monotherapy in patients with 2 diabetes exhibiting inadequate glycemic control (A1C 7–11%). RESEARCH DESIGN AND METHODS This double-blind placebo-controlled paralleled study randomized 302 (mean A1C 8.3%) on 1.5 g/day)...
Abstract Purpose: The c-MET receptor tyrosine kinase plays important roles in the formation, progression, and dissemination of human cancer presents an attractive therapeutic target. This study describes preclinical characterization INCB28060, a novel inhibitor kinase. Experimental Design: Studies were conducted using series vitro vivo biochemical biological experiments. Results: INCB28060 exhibits picomolar enzymatic potency is highly specific for with more than 10,000-fold selectivity over...
Alterations in fibroblast growth factor receptor (FGFR) genes have been identified as potential driver oncogenes. Pharmacological targeting of FGFRs may therefore provide therapeutic benefit to selected cancer patients, and proof-of-concept has established early clinical trials FGFR inhibitors. Here, we present the molecular structure preclinical characterization INCB054828 (pemigatinib), a novel, selective inhibitor 1, 2, 3, currently phase 2 trials. pharmacokinetics pharmacodynamics were...
Blocking the activity of programmed cell death protein 1 (PD-1) inhibitory receptor with therapeutic antibodies against either ligand (PD-L1) or PD-1 itself has proven to be an effective treatment modality for multiple cancers. Contrasting antibodies, small molecules could demonstrate increased tissue penetration, distinct pharmacology, and potentially enhanced antitumor activity. Here, we describe identification characterization INCB086550, a novel, oral, small-molecule PD-L1 inhibitor. In...
The matrix components responsible for cartilage mechanical properties, type II collagen and aggrecan, are degraded in osteoarthritis through proteolytic cleavage by metalloproteinases (MMPs) aggrecanases, respectively. We now show that aggrecan may serve to protect from degradation. Although freeze-thawed depleted of was completely following incubation with MMP-1, intact not. Using interleukin-1-stimulated bovine nasal explants where depletion occurs during the first week culture, followed...
Overexpression and activating mutations of ErbB family members have been implicated in the development progression a variety tumor types. Cleavage HER2 receptor by an as yet unidentified ectodomain sheddase has shown to liberate extracellular domain (ECD) leaving fragment with constitutive kinase activity that can provide ligand-independent growth survival signals cell. This process is clinically relevant since ECD serum levels metastatic breast cancer patients are associated poorer...
Abstract Purpose: ErbB receptor signaling pathways are important regulators of cell fate, and their dysregulation, through (epi)genetic alterations, plays an etiologic role in multiple cancers. ligands synthesized as membrane-bound precursors that cleaved by members the ADAM family zinc-dependent metalloproteases. This processing, termed ectodomain shedding, is essential for functional activation ligands. Recent studies suggest elevated levels may circumvent effectiveness ErbB-targeted...
Abstract Angioimmunoblastic T‐cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting role antigenic drive in its development. Genetically, it characterized by stepwise acquisition somatic mutations, early mutations involving epigenetic regulators ( TET2 , DNMT3A ) occurring haematopoietic stem cells, subsequent changes signaling molecules RHOA VAV1 PLCG1, CD28 critical for biology. To search evidence potential...
Aberrant activation of FGFR has been linked to the pathogenesis many tumor types. Selective inhibition emerged as a promising approach for cancer treatment. Herein, we describe discovery compound 38 (INCB054828, pemigatinib), highly potent and selective inhibitor FGFR1, FGFR2, FGFR3 with excellent physiochemical properties pharmacokinetic profiles. Pemigatinib received accelerated approval from U.S. Food Drug Administration treatment adults previously treated, unresectable locally advanced...
Abstract MicroRNAs (miRNAs) are a class of evolutionarily conserved, 18–25 nucleotide non-coding sequences that post-transcriptionally regulate gene expression. Recent studies implicated their roles in the regulation neuronal functions, such as learning, cognition and memory formation. Here we report miR-218 inhibits heroin-induced behavioral plasticity. First, network propagation-based method was used to predict candidate miRNAs played potential key regulating drug addiction-related genes....
The Proviral Integration site of Moloney murine leukemia virus (PIM) serine/threonine protein kinases are overexpressed in many hematologic and solid tumor malignancies play central roles intracellular signaling networks important tumorigenesis, including the Janus kinase–signal transducer activator transcription (JAK/STAT) phosphatidylinositol 3-kinase (PI3K)/AKT pathways. three PIM kinase isozymes (PIM1, PIM2, PIM3) share similar downstream substrates with other key oncogenic have...
CDK2 is a critical regulator of the cell cycle. For variety human cancers, dysregulation CDK2/cyclin E1 can lead to tumor growth and proliferation. Historically, early efforts develop inhibitors with clinical applications proved unsuccessful due challenges in achieving selectivity over off-target CDK isoforms associated toxicity. In this report, we describe discovery (4-pyrazolyl)-2-aminopyrimidines as potent class that display CDKs 1, 4, 6, 7, 9. SAR studies led identification compound 17,...
miR-16 is known to be abnormally expressed in hepatocellular carcinoma (HCC) cells, and the overexpression of inhibits proliferation, invasion metastasis various cancer cells. MicroRNAs (miRNAs or miRs) are closely related HCC. The present study aimed explore effects on HCC elucidate mechanisms involved. A cell line with moderate levels miR‑16 expression was selected from SMMC-7721, HepG2, SK-Hep-1 Huh‑7 cells validated by reverse transcription-PCR (RT-PCR). viability were determined MTT...
Bromodomain and extraterminal domain (BET) proteins regulate the expression of many cancer-associated genes pathways; BET inhibitors have demonstrated activity in diverse models hematologic solid tumors. We report preclinical characterization INCB054329, a structurally distinct inhibitor that has been investigated phase I clinical trials.We used multiple myeloma to investigate vulnerabilities created by INCB054329 treatment could inform rational combinations.In addition c-MYC, decreased...
A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3Kδ) led to the discovery of clinical INCB050465 (20, parsaclisib). The unique structure 20 contains pyrazolopyrimidine hinge-binder in place purine motif that is present other PI3Kδ inhibitors, such as idelalisib (1), duvelisib (2), and INCB040093 (3, dezapelisib). Parsaclisib (20) potent highly selective inhibitor with drug-like ADME properties exhibited an excellent...
TYRO3, AXL, and MERTK constitute the TAM family of receptor tyrosine kinases, which play important roles in tumor growth, survival, cell adhesion, as well innate immunity, phagocytosis, immune-suppressive activity. Therefore, targeting both AXL kinases may directly impact growth relieve immunosuppression. We describe here discovery INCB081776, a potent selective dual inhibitor that is currently phase 1 clinical trials. In cellular assays, INCB081776 effectively blocked autophosphorylation or...
The clinical use of first-generation phosphoinositide 3-kinase (PI3K)<i>δ</i> inhibitors in B-cell malignancies is hampered by hepatotoxicity, requiring dose reduction, treatment interruption, and/or discontinuation therapy. In addition, potential molecular mechanisms which resistance to this class drugs occurs have not been investigated. Parsaclisib (INCB050465) a potent and selective next-generation PI3K<i>δ</i> inhibitor that differs structure from has shown encouraging anti–B-cell tumor...
The inhibition of mutant KRAS proteins has emerged as a promising approach for treating KRAS-driven cancers, evidenced by the clinical success G12C inhibitors. G12D, most common mutant, promises significant expansion addressable patient population; however, reduced nucleophilicity aspartate compared to cysteine poses challenges in balancing sufficient potency with ADME properties support oral exposure. Herein, we describe discovery G12D inhibitor 23 (INCB159020), which achieves exposure...
Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL unclear few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis frequent problem. Clinicopathologic characteristics 35 retrospective cases were investigated the aim improving diagnosis and find associated etiology. Because relatively low number leukemic cells in peripheral blood bone marrow, can be missed; therefore, it important perform...
The gastrointestinal tract (GIT) is the most common anatomic site of extranodal non-Hodgkin lymphoma (NHL) involvement. classification criteria have changed in recent decades, and few large-sample studies regarding subtype analysis been performed this site.Therefore, present study was conducted to analyze histological distribution GIT.All patients a single institution with diagnosis primary NHL GIT were enrolled between January 2007 April 2014. categorized according WHO (2008) tumors...