HJC0152 / The University of Texas, UT MD Anderson Cancer Center, Tianjin Medical University Cancer Institute and Hospital - LARVOL DELTA

STAT3 Increases CVB3 Replication and Acute Pancreatitis and Myocarditis Pathology via Impeding Nuclear Translocation of STAT1 and Interferon-Stimulated Gene Expression. (PubMed, Int J Mol Sci) - "The in vivo administration of HJC0152, a pharmaceutical STAT3 inhibitor, mitigated the viral-induced AP and myocarditis pathology via increasing the IFNβ as well as ISG expression on day 3 p.i. and reducing the viral load in multi-organs. These findings define STAT3 as a negative regulator of the type I IFN response via impeding the nuclear STAT1 translocation that otherwise triggers ISG induction in infected pancreases and hearts. Our findings identify STAT3 as an antagonizing factor of the IFN-STAT1 signaling pathway and provide a potential therapeutic target for viral-induced AP and myocarditis."

Journal • Cardiovascular • Fibrosis • Immunology • Inflammation • Pancreatitis • IFNB1 • SOCS3 • STAT1 • STAT3

Development of HJC0152, its analogs and protein degraders to modulate STAT3 for triple-negative breast cancer therapy (AACR 2023) - "Our data indicate that HJC0152-based analogs and protein degraders can suppress breast cancer cell proliferation, likely through targeting STAT3 signaling pathway. Future experiments will determine the molecular prolife of promising molecules as well as assess their in vivo anticancer efficacy using xenograft models."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • STAT3

Imaging of Primary and Metastatic Tumors Treated with Radiotherapy-Directed Antigen-Capturing Nanoparticles, Reducing Metastasis-Seeding and Colonization, under PDL-1 Blockade (ASTRO 2022) - "Screens: N/A/21Purpose/Objective(s): We tested a treatment combining radiotherapy with antigen-capturing nanoparticles (AC-NPs; 112 ± 73 nm) containing digitoxin and anti-STAT-3 inhibitor (HJC0152) encapsulated in nanocapsules (545 ± 24 nm), which release their contents upon radiation exposure... Our CT-detectable nanocapsules will lead to better diagnosis and tumor treatment."

Breast Cancer • Oncology • Solid Tumor • CD8 • FLT1 • STAT3

Smart hypoxia-responsive transformable and charge-reversible nanoparticles for the deep penetration and tumor microenvironment modulation of pancreatic cancer. (PubMed, Biomaterials) - "Hence, we design and construct an aptamer-decorated hypoxia-responsive nanoparticle s(DGL)@Apt co-loading gemcitabine monophosphate and STAT3 inhibitor HJC0152. Meanwhile, HJC0152 inhibits overactivated STAT3 in both tumor cells and tumor stroma, softens the stroma barrier, and reeducates the TME into an immune-activated state. This smart codelivery strategy provides an inspiring opportunity in PDAC treatment."

Biomarker • Journal • Tumor microenvironment • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Development of HJC0152-based proteolysis-targeting chimera degraders for breast cancer therapy (AACR 2022) - "These compounds are currently being investigated for breast cancer cell migration and invasion, and will be evaluated for the in vivo inhibition of tumor growth and metastasis in different mouse models. This project is supported by NIH/NCI Awards R01CA226001 and R01CA231150 to Q.S. and J.Z."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment. (PubMed, Small) - "In this work, a versatile drug delivery system is developed that can coencapsulate two prodrugs modified from gemcitabine (GEM) and a signal transducer and activator of transcription 3 (STAT3) inhibitor (HJC0152), and the gradient pH variation is further sensed in the TME of PDAC to achieve a higher penetration by reversing its surficial charges. Furthermore, cytidine deaminase (CDA) and α-smooth muscle actin (α-SMA) expression can be downregulated, plus the lipid modification of GEM, the drug resistance of GEM can be greatly relieved. Based on the above design, a synergetic therapeutic efficacy in PDAC treatment can be achieved to provide more opportunity for clinical applications."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension. (PubMed, Int J Mol Sci) - "Using a specific siRNA and a potent pharmacological STAT3 inhibitor (STAT3i, HJC0152), we found that SERCA2a potentiated BMPR2 expression by repressing STAT3 activity in PASMCs and PAECs...Finally, we used cardiac magnetic resonance imaging to measure RV function and found that therapies using AAV1.hSERCA2a alone or combined with STAT3i significantly inhibited RV structural and functional changes in PNT/MCT-induced PAH. In conclusion, our study demonstrated that combination therapies using SERCA2a gene transfer with a STAT3 inhibitor could represent a new promising therapeutic alternative to inhibit PAH and to restore BMPR2 expression by limiting STAT3 activity."

Combination therapy • Journal • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • MRI

[VIRTUAL] Treating estrogen receptor (ER)-negative and triple-negative breast cancer by targeting STAT3 signaling with putative STAT3 inhibitors (AACR 2021) - "ENBCs do not respond to selective ER modulators such as tamoxifen...We recently developed a putative STAT3 inhibitor, HJC0152, and a series of HJC0152-based analogues as orally bioavailable STAT3 inhibitors...Our current research supports the notion that JMX0804 suppresses breast cancer growth by inhibiting breast cancer cell proliferation and inducing apoptosis via mediating STAT3 signaling. JMX0804 is currently undergoing further characterization for breast cancer metastasis and mechanisms of action as well as optimization to improve drug properties including potency and safety profile."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER

[VIRTUAL] Examination of HJC0152, a putative modulator of glucose and energy metabolism, for mammary cancer prevention (AACR-II 2020) - "This study was supported by a NIH/NCI PREVENT Program fund. *Current Affiliation: LSUHSC."

Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

HJC0152 suppresses human non-small-cell lung cancer by inhibiting STAT3 and modulating metabolism. (PubMed, Cell Prolif) - "HJC0152 reduces cellular capacity to scavenge free radicals, leading to ROS generation and accumulation and apoptosis. This study provides a rationale for further developing HJC0152 as a potential therapy for NSCLC and provides insights into the mechanisms by which HJC0152 exerts its anti-cancer effects."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A novel STAT3 inhibitor, HJC0152, exerts potent antitumor activity in glioblastoma. (PubMed, Am J Cancer Res) - "Furthermore, HJC0152 inhibited the growth of glioblastoma xenograft tumors in vivo. This study provides a rationale for developing HJC0152 as a STAT3-targeting therapy for treating human glioblastoma in the future."

Journal

Chemoprevention of breast cancer by targeting glucose metabolism with HJC0152 (AACR 2019) - "In addition, HJC0152 can serve as a molecular probing tool for elucidating the key factors driving the development of breast cancer in the context of metabolic dysregulation and diseases. This work was supported by grant R01CA226001 from the NIH/NCI."