A5055734529- Cancer Mechanisms and Therapy
- Cytokine Signaling Pathways and Interactions
- Pancreatic and Hepatic Oncology Research
- Biochemical and Molecular Research
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- Mast cells and histamine
- Dermatology and Skin Diseases
- Synthesis and biological activity
- Lymphoma Diagnosis and Treatment
- Tuberculosis Research and Epidemiology
- Quinazolinone synthesis and applications
- Protein Tyrosine Phosphatases
- Psoriasis: Treatment and Pathogenesis
East China Normal University
2022-2024
Viva Biotech (China)
2024
Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Unfortunately, targeting STAT3 with small molecules has proven to be very challenging, for full activation STAT3, the cooperative phosphorylation both tyrosine 705 (Tyr705) serine 727 (Ser727) needed. Further, a selective inhibitor dual not been developed. Here, we identified low nanomolar potency highly small-molecule that simultaneously inhibits Tyr705 Ser727 phosphorylation. YY002...
Abstract Purpose: Pancreatic cancer is the worst prognosis among all human cancers, and novel effective treatments are urgently needed. Signal transducer activator of transcription 3 (STAT3) has been demonstrated as a promising target for pancreatic cancer. Meanwhile, selectively targeted STAT3 with small molecule remains challenging. Experimental Design: To specifically identify inhibitors, more than 1.3 million compounds were screened by structure-based virtual screening confirmed direct...
Osteosarcoma is one of the most common malignant bone tumors. However, treatment and clinical outcomes osteosarcoma have hardly changed over past three decades due to comprehensive heterogeneity higher rate mutation osteosarcoma. Recent studies shown that STAT3 has potential suppress proliferation metastasis In this study, a novel class 2-amino-3-cyanothiophene derivatives were designed synthesized inhibit by targeting STAT3. Representative compound 6f showed potent antiproliferative effects...
Increasing evidence has demonstrated that STAT3 phosphorylation at Tyr705 and Ser727 is closely associated with the progression poor prognosis of pancreatic cancer. Herein, we report function-based screening, SAR studies, biological activity evaluation a series novel dual inhibitors an indole-containing tetra-aromatic heterocycle scaffold. Our efforts led to discovery optimal compound 4c among investigated ones, showing desirable ADME properties highly potent antitumor activities in vitro...
Natural killer/T-cell lymphoma (NKTL) is an uncommon malignancy with poor prognosis and limited therapeutic options. Activating mutations of signal transducer activator transcription 3 (STAT3) are frequently found in patients NKTL, suggesting that targeted inhibition STAT3 a potential option for this disease. Here, we have developed small molecule drug WB737 as novel potent inhibitor directly binds to the STAT3-Src homology 2 domain high affinity. In addition, binding affinity 250-fold...
<p>Supplementary Methods</p>
<p>Fig. S1. Structure-based ligand discovery of STAT3 inhibitorsFig. S2. Surface plasmon resonance analysis interactions between WB436B to STATfamily proteinsFig. S3. The biology evaluation inactive analogue WB345Fig. S4. mutation in SH2 domain directly inhibited transcriptionalactivitiesFig. S5. induced pancreatic cancer cells apoptosisFig. S6. knockdown reduced PDAC growth and colony formationFig. S7. displayed little cytotoxicity stable cells.Fig. S8. depletion the cellsFig. S9....
<p>Fig. S1. Structure-based ligand discovery of STAT3 inhibitorsFig. S2. Surface plasmon resonance analysis interactions between WB436B to STATfamily proteinsFig. S3. The biology evaluation inactive analogue WB345Fig. S4. mutation in SH2 domain directly inhibited transcriptionalactivitiesFig. S5. induced pancreatic cancer cells apoptosisFig. S6. knockdown reduced PDAC growth and colony formationFig. S7. displayed little cytotoxicity stable cells.Fig. S8. depletion the cellsFig. S9....
<p>Supplementary Methods</p>
<div>AbstractPurpose:<p>Pancreatic cancer is the worst prognosis among all human cancers, and novel effective treatments are urgently needed. Signal transducer activator of transcription 3 (STAT3) has been demonstrated as a promising target for pancreatic cancer. Meanwhile, selectively targeted STAT3 with small molecule remains challenging.</p>Experimental Design:<p>To specifically identify inhibitors, more than 1.3 million compounds were screened by structure-based...
<div>AbstractPurpose:<p>Pancreatic cancer is the worst prognosis among all human cancers, and novel effective treatments are urgently needed. Signal transducer activator of transcription 3 (STAT3) has been demonstrated as a promising target for pancreatic cancer. Meanwhile, selectively targeted STAT3 with small molecule remains challenging.</p>Experimental Design:<p>To specifically identify inhibitors, more than 1.3 million compounds were screened by structure-based...