scholarly journals The same site on the integrase-binding domain of lens epithelium–derived growth factor is a therapeutic target for MLL leukemia and HIV

Blood ◽  
2014 ◽  
Vol 124 (25) ◽  
pp. 3730-3737 ◽  
Author(s):  
Marcelo J. Murai ◽  
Jonathan Pollock ◽  
Shihan He ◽  
Hongzhi Miao ◽  
Trupta Purohit ◽  
...  
Keyword(s):  
Growth Factor ◽  
Small Molecule ◽  
Therapeutic Target ◽  
Small Molecule Inhibitors ◽  
Binding Domain ◽  
Lens Epithelium ◽  
New Drugs ◽  
Structural Studies ◽  
Key Points

Key Points Inhibiting LEDGF interaction with a novel fragment of MLL represents an attractive approach to develop new drugs for MLL leukemias. Structural studies reveal a new pocket on the LEDGF IBD suitable for targeting by small-molecule inhibitors.

scholarly journals Research Progress of Small Molecule VEGFR/c-Met Inhibitors as Anticancer Agents (2016–Present)

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2666 ◽  
Author(s):  
Qian Zhang ◽  
Pengwu Zheng ◽  
Wufu Zhu
Keyword(s):  
Growth Factor ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Small Molecule Inhibitors ◽  
Growth Factor Receptor ◽  
New Drugs ◽  
Research Progress ◽  
Chemical Structures ◽  
High Affinity Receptor ◽  
Dual Target

Vascular endothelial growth factor receptor 2 (VEGFR-2) binds to VEGFR-A, VEGFR-C and VEGFR-D and participates in the formation of tumor blood vessels, mediates the proliferation of endothelial cells, enhances microvascular permeability, and blocks apoptosis. Blocking or downregulating the signal transduction of VEGFR is the main way to discover new drugs for many human angiogenesis-dependent malignancies. Mesenchymal epithelial transfer factor tyrosine kinase (c-Met) is a high affinity receptor for hepatocyte growth factor (HGF). Abnormal c-Met signaling plays an important role in the formation, invasion and metastasis of human tumors. Therefore, the HGF/c-Met signaling pathway has become a significant target for cancer treatment. Related studies have shown that the conduction of the VEGFR and c-Met signaling pathways has a synergistic effect in inducing angiogenesis and inhibiting tumor growth. In recent years, multi-target small molecule inhibitors have become a research hotspot, among which the research of VEGFR and c-Met dual-target small molecule inhibitors has become more and more extensive. In this review, we comprehensively summarize the chemical structures and biological characteristics of novel VEGFR/c-Met dual-target small-molecule inhibitors in the past five years.

Discovery of Small-Molecule Inhibitors Selectively Targeting the DNA-Binding Domain of the Human Androgen Receptor

2014 ◽  
Vol 57 (15) ◽  
pp. 6458-6467 ◽  
Author(s):  
Huifang Li ◽  
Fuqiang Ban ◽  
Kush Dalal ◽  
Eric Leblanc ◽  
Kate Frewin ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Dna Binding ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Human Androgen Receptor

scholarly journals Overexpression of the Lens Epithelium-Derived Growth Factor/p75 Integrase Binding Domain Inhibits Human Immunodeficiency Virus Replication

2006 ◽  
Vol 80 (23) ◽  
pp. 11498-11509 ◽  
Author(s):  
Jan De Rijck ◽  
Linos Vandekerckhove ◽  
Rik Gijsbers ◽  
Anneleen Hombrouck ◽  
Jelle Hendrix ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Cell Lines ◽  
Fusion Proteins ◽  
Binding Domain ◽  
Lens Epithelium ◽  
Integration Step ◽  
Hiv Replication ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We initially identified lens epithelium-derived growth factor/p75 (LEDGF/p75) as a binding partner of human immunodeficiency virus type 1 (HIV-1) integrase. To investigate the role of LEDGF/p75 in HIV replication and its potential as a new antiviral target, we stably overexpressed two different fragments containing the integrase binding domain (IBD) of LEDGF/p75 fused to enhanced green fluorescent protein (eGFP). HIV-1 replication was severely inhibited by overexpression of the eGFP-IBD fusion proteins, while no inhibition was observed in cell lines overexpressing the interaction-deficient D366A mutant. Quantitative PCR pinpointed the block to the integration step, whereas nuclear import was not affected. Competition of the IBD fusion proteins with endogenous LEDGF/p75 for binding to integrase led to a potent defect in HIV-1 replication in both HeLaP4- and MT-4-derived cell lines. A previously described diketo acid-resistant HIV-1 strain remained fully susceptible to inhibition, suggesting that this strategy will also work in patients who harbor strains resistant to the current experimental integrase inhibitors. These data support LEDGF/p75 as an important cofactor for HIV replication and provide proof of concept for the LEDGF/p75-integrase interaction as a novel target for treating HIV-1 infection.

Structure-based discovery of novel small molecule inhibitors of platelet-derived growth factor-B

2020 ◽  
Vol 94 ◽  
pp. 103374 ◽  
Author(s):  
Omid Zarei ◽  
Niki Sarri ◽  
Siavoush Dastmalchi ◽  
Fateme Zokai ◽  
Natalia Papadopoulos ◽  
...  
Keyword(s):  
Growth Factor ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Platelet Derived Growth Factor ◽  
Factor B

scholarly journals Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction

2010 ◽  
Vol 53 (5) ◽  
pp. 2215-2226 ◽  
Author(s):  
Ashley Jarvis ◽  
Charles K. Allerston ◽  
Haiyan Jia ◽  
Birger Herzog ◽  
Acely Garza-Garcia ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Vascular Endothelial ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

scholarly journals Enhancing functional platelet release in vivo from in vitro–grown megakaryocytes using small molecule inhibitors

2018 ◽  
Vol 2 (6) ◽  
pp. 597-606 ◽  
Author(s):  
Danuta Jarocha ◽  
Karen K. Vo ◽  
Randolph B. Lyde ◽  
Vincent Hayes ◽  
Rodney M. Camire ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Key Points ◽  
Drug Treatments ◽  
Platelet Release

Key PointsDrugs shown to enhance megakaryocyte ploidy and size variably effect terminal injury and apoptosis of in vitro–grown megakaryocytes. The number of functional platelets released in vivo from infused megakaryocytes can be enhanced by these drug treatments.

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