☆ 4.7 Article

Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors

BIOORGANIC CHEMISTRY (2023)

Related references

Note: Only part of the references are listed.

Article Chemistry, Medicinal

Discovery of Macrocycle-Based HPK1 Inhibitors for T-Cell-Based Immunotherapy

Ming-Shu Wang et al.

Summary: In this study, a series of macrocycle-based HPK1 inhibitors were designed via a conformational constraint strategy. The candidate compound 5i exhibited potent HPK1 inhibition with high selectivity against GLK. Compound 5i also showed good oral bioavailability and metabolic stability, and demonstrated a synergistic effect with anti-PD-1 in tumor mouse models, highlighting its potential in immunotherapy.

JOURNAL OF MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Chemistry, Medicinal

Design and Synthesis of Functionally Active 5-Amino-6-Aryl Pyrrolopyrimidine Inhibitors of Hematopoietic Progenitor Kinase 1

Rebecca A. Gallego et al.

Summary: Immune activating agents have significant potential as cancer therapeutics, and current research focuses on expanding the range of available therapeutics by targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1), as a negative regulator of immune signaling, is a highly promising target for cancer treatment. This study presents the discovery and optimization of novel amino-6-aryl pyrrolopyrimidine inhibitors of HPK1, starting from hits identified through virtual screening. Key aspects of this research include structure-based drug design, analysis of normalized B-factors, and optimization of lipophilic efficiency.

JOURNAL OF MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Chemistry, Medicinal

Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1)

Bryan K. Chan et al.

Summary: HPK1, identified as a negative regulator of T-cell activation, has potential implications in tumor therapy. Through structure-based drug design, a series of small molecule inhibitors of HPK1 were discovered with significantly improved kinase selectivity, showing potential therapeutic value in tumor treatment.

ACS MEDICINAL CHEMISTRY LETTERS (2022)

Add to Collection

Article Chemistry, Medicinal

Hematopoietic Progenitor Kinase 1 in Tumor Immunology: A Medicinal Chemistry Perspective

Qiangsheng Zhu et al.

Summary: HPK1, a negative regulator of immune cells, has emerged as a promising target for tumor immunotherapy. Inhibitors and PROTACs targeting HPK1 have been developed to enhance immune response and inhibit tumor growth.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

Add to Collection

Article Oncology

Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor

Dan You et al.

Summary: This study identified a novel, potent, and selective HPK1 small molecule kinase inhibitor called Compound K (CompK), which significantly improved human T-cell immune responses in the tumor microenvironment and showed significant synergy with anti-PD-1 therapy. Animal model studies demonstrated improved immune responses and antitumor efficacy with CompK in combination with anti-PD-1, suggesting its potential as a novel pharmacological agent for cancer treatment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

Add to Collection

Article Chemistry, Medicinal

Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1

Andrew P. Degnan et al.

Summary: The study presents a novel HPK1 inhibitor which, when used in combination in a colorectal cancer model, significantly enhances the efficacy of anti-PD1 treatment.

ACS MEDICINAL CHEMISTRY LETTERS (2021)

Add to Collection

Article Chemistry, Medicinal

Discovery of Diaminopyrimidine Carboxamide HPK1 Inhibitors as Preclinical Immunotherapy Tool Compounds

Brandon A. Vara et al.

Summary: HPK1 is a negative immune regulator primarily expressed in hematopoietic cells, and its loss can enhance T cell signaling and cytokine production, leading to tumor growth inhibition in vivo. The structurally enabled discovery of novel, potent, and selective HPK1 inhibitors, with a carboxamide moiety crucial for enhanced potency and selectivity, holds promise as an immunotherapeutic target.

ACS MEDICINAL CHEMISTRY LETTERS (2021)

Add to Collection

Review Immunology

Opportunities for Small Molecules in Cancer Immunotherapy

Sabina Y. van der Zanden et al.

TRENDS IN IMMUNOLOGY (2020)

Add to Collection

Review Immunology

A guide to cancer immunotherapy: from T cell basic science to clinical practice

Alex D. Waldman et al.

NATURE REVIEWS IMMUNOLOGY (2020)

Add to Collection

Article Multidisciplinary Sciences

Critical role of kinase activity of hematopoietic progenitor kinase 1 in anti-tumor immune surveillance

Jinqi Liu et al.

PLOS ONE (2019)

Add to Collection

Article Chemistry, Multidisciplinary

Identification of compound D2923 as a novel anti-tumor agent targeting CSF1R

Ying-Qiang Liu et al.

ACTA PHARMACOLOGICA SINICA (2018)

Add to Collection

Review Medicine, General & Internal

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

Michael A. Postow et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Add to Collection

Article Cell Biology

The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the Regulation of T Cell Function

Sairy Hernandez et al.

CELL REPORTS (2018)

Add to Collection

Article Medicine, General & Internal

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

J. Larkin et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

Add to Collection

Article Biochemistry & Molecular Biology

Down-regulation of B Cell Receptor Signaling by Hematopoietic Progenitor Kinase 1 (HPK1)-mediated Phosphorylation and Ubiquitination of Activated B Cell Linker Protein (BLNK)

Xiaohong Wang et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Add to Collection

Article Chemistry, Medicinal

Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia

Jing Liu et al.

ACS MEDICINAL CHEMISTRY LETTERS (2012)

Add to Collection

Article Cell Biology

Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation

Remi Lasserre et al.

JOURNAL OF CELL BIOLOGY (2011)

Add to Collection

Article Chemistry, Medicinal

Intramolecular Hydrogen Bonding in Medicinal Chemistry

Bernd Kuhn et al.

JOURNAL OF MEDICINAL CHEMISTRY (2010)

Add to Collection

Article Medicine, General & Internal

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi et al.

NEW ENGLAND JOURNAL OF MEDICINE (2010)

Add to Collection

Article Immunology

Hematopoietic Progenitor Kinase 1 Is a Negative Regulator of Dendritic Cell Activation

Saba Alzabin et al.

JOURNAL OF IMMUNOLOGY (2009)

Add to Collection

Article Immunology

Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell-mediated immune responses

Jr-Wen Shui et al.

NATURE IMMUNOLOGY (2007)

Add to Collection

Article Biochemistry & Molecular Biology

Activation of hematopoietic progenitor kinase 1 involves relocation, autophosphorylation, and transphosphorylation by protein kinase D1

R Arnold et al.

MOLECULAR AND CELLULAR BIOLOGY (2005)

Add to Collection

Article Hematology

Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2-induced fos gene transcription

S Sawasdikosol et al.

BLOOD (2003)

Add to Collection

Article Biochemistry & Molecular Biology

Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling

P Ling et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2001)

Add to Collection

Article Immunology

HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1

J Liou et al.

IMMUNITY (2000)

Add to Collection

© Peeref 2019-2024. All rights reserved.