Targeting non-receptor tyrosine kinases using small molecule inhibitors: an overview of recent advances

Hojjat‐Farsangi, Mohammad

doi:10.3109/1061186x.2015.1068319

Cited by 16 publications

(9 citation statements)

References 192 publications

(245 reference statements)

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“…The complexes were analyzed for interactions, and their 3D images were taken by using visualizing tool PyMol. The docking protocol predicted the same conformation as was present in the crystal structure with an RMSD value within the allowed range of 2.0 Å 45,46 . The superposition of the docked conformation and cocrystalized ligand is shown.…”

Section: Modelingmentioning

confidence: 80%

Untitled

2018

IJPSR

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In the field of the preparation of chemotherapeutic agents with new mechanism distinct from currently approved drugs is important. However, the clinically effective approved small inhibitor molecule is still lacking. Previous reports indicated that 4-aryl-2-hydrazinothiazole derivatives provided a useful start point to develop HAT inhibitors (histone acetyltransferase). Consequently, preparation and biological evaluation of a focused library of 4-aryl-2-hydrazinothiazole based derivatives as useful as anti-cancer agents. Synthesis of 4-aryl-2-hydrazinothiazoles (1a-d), (2a-d), (3a-c), (4a-b), (5a-b), (6a-b) studied by either conventional method and free solvent microwave one-pot method, and the synthesized compounds were proved by spectroscopic methods (IR, 1 HNMR, 13 CNMR, GC-Ms, and elemental analysis). The activity against different cancer cell lines and the antimicrobial activities different organisms also studied, and all of the synthesized compounds were of high activity as an antibacterial for gram positive and gram negative; however, it showed also an antifungal activity were the most active compounds were 4a, 4b, 5b, 6a. It was found that all of the prepared thiazoles derivatives were active toward many cell lines (breast, liver, and prostate) where the more active compounds were 4a, 4b, and 6a. Molecular docking studies guided and proved the biological activities of these novel 4-aryl-2-hydrazinothiazoles.

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Section: Modelingmentioning

confidence: 80%

Untitled

2018

IJPSR

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“…Dysregulation of PTK activity (e.g. overexpression) has been implicated in tumourigenesis, and the development of tyrosine kinase inhibitors (TKIs) has been one of the most important recent advances in oncology [7–9]. …”

Section: Introductionmentioning

confidence: 99%

Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond

King-Wing

McAdoo

Tam

2017

Nephrology Dialysis Transplantation

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Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease. SYK is implicated in the pathogenesis of ANCA-associated GN. SYK, BTK, PDGFR, EFGR, DDR1 and Janus kinase are implicated in the pathogenesis of lupus nephritis. A representative animal model of IgA nephropathy (IgAN) is lacking. Based on the results from in vitro and human renal biopsy study results, a phase II clinical trial is ongoing to evaluate the efficacy and safety of fostamatinib (an oral SYK inhibitor) in high-risk IgAN patient. Various tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment. Clinical trials of TKIs in GN may be justified given their long-term safety data. In this review we will discuss the current unmet medical needs in GN treatment and research as well as the current stage of development of TKIs in GN treatment and propose an accelerated translational research approach to investigate whether selective inhibition of tyrosine kinase provides a safer and more efficacious option for GN treatment.

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“…These agents are more specific for tumor cells than normal cells [1]. Small molecule inhibitors (SMIs), including kinase inhibitors are potent agents for the treatment of cancer and autoimmune diseases [2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…These agents induce apoptosis of tumor cells through blocking molecules involved in cell survival [9].…”

Section: Introductionmentioning

confidence: 99%

Ibrutinib-A double-edge sword in cancer and autoimmune disorders

Kokhaei

Jadidi‐Niaragh

Jahromi

et al. 2015

Journal of Drug Targeting

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Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells. In addition to inhibitory effects, recent studies have shown that ibrutinib has multiple immunomodulatory effects. It binds covalently to IL-2 inducible tyrosine kinase (Itk) in T lymphocytes and suppresses the survival of T-helper (Th) 2 cells. This changes the balance of Th1/Th2 cells toward Th1 subset, which are the main immune cells targeting tumor cells. The dual activity of ibrutinib has paid a great attention and several studies are evaluating the anti-tumor and immunomodulatory effects in cancer, autoimmune disorders and infectious diseases. In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk.

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Targeting non-receptor tyrosine kinases using small molecule inhibitors: an overview of recent advances

Cited by 16 publications

References 192 publications

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Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond

Ibrutinib-A double-edge sword in cancer and autoimmune disorders

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