Src Kinase Inhibitors: Promising Cancer Therapeutics?

2012 ◽  
Vol 17 (2) ◽  
pp. 145-159 ◽  
Author(s):  
Helen Creedon ◽  
Valerie G . Brunton
Keyword(s):  
Kinase Inhibitors ◽  
Src Kinase ◽  
Cancer Therapeutics

scholarly journals Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

2021 ◽  
Vol 22 (2) ◽  
pp. 493
Author(s):  
Christos Vallilas ◽  
Panagiotis Sarantis ◽  
Anastasios Kyriazoglou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Gastrointestinal Neoplasms ◽  
Mesenchymal Tumors ◽  
Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).

scholarly journals Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 576
Author(s):  
Sofia Giacosa ◽  
Catherine Pillet ◽  
Irinka Séraudie ◽  
Laurent Guyon ◽  
Yann Wallez ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Renal Carcinoma ◽  
Kinase Inhibitors ◽  
Ex Vivo ◽  
Cancer Therapeutics ◽  
Carcinoma Cells ◽  
Wild Type ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Renal Carcinoma Cells

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL− cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug–gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC.

Src Kinase Inhibitors: An Update on Patented Compounds

2011 ◽  
Vol 18 (33) ◽  
pp. 5061-5078 ◽  
Author(s):  
S. Schenone ◽  
C. Brullo ◽  
F. Musumeci ◽  
M. Radi ◽  
D. Castagnolo
Keyword(s):  
Kinase Inhibitors ◽  
Src Kinase

3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases

2005 ◽  
Vol 13 (15) ◽  
pp. 4704-4712 ◽  
Author(s):  
Ram Thaimattam ◽  
Pankaj R. Daga ◽  
Rahul Banerjee ◽  
Javed Iqbal
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Src Kinase ◽  
3D Qsar ◽  
Qsar Studies ◽  
Abl Kinases

Design, Synthesis and Pharmacokinetic Evaluation of a Novel Series of Triazole-Based Src Kinase Inhibitors with Anti-proliferative Activity

2011 ◽  
Vol 8 (1) ◽  
pp. 9-13
Author(s):  
Shaojun Chen ◽  
Chuansheng Guo ◽  
Shiting Shi ◽  
Yanyan Shi ◽  
Du Fang ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Kinase Inhibitors ◽  
Src Kinase ◽  
Design Synthesis ◽  
Pharmacokinetic Evaluation

Synthesis and antiproliferative and c-Src kinase inhibitory activities of cinnamoyl- and pyranochromen-2-one derivatives

2013 ◽  
Vol 91 (8) ◽  
pp. 741-754 ◽  
Author(s):  
Karam Chand ◽  
Amir Nasrolahi Shirazi ◽  
Preeti Yadav ◽  
Rakesh K. Tiwari ◽  
Meena Kumari ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Human Cancer ◽  
Src Kinase ◽  
Cancer Cell Lines ◽  
Ovarian Adenocarcinoma ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of 6- and 8-cinnamoylchromen-2-one and dihydropyranochromen-2-one derivatives were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines, i.e., ovarian adenocarcinoma (SK-OV-3), leukemia (CCRF-CEM), and breast carcinoma (MCF-7). In general, 8-cinnamoylchromen-2-one derivatives were found to have higher antiproliferative activity against the cancer cells when compared with 6-cinnamoyl analogues. Among all of the hybrid chromen-2-one − chalcone/flavanone compounds, a 7-hydroxy-8-cinnamoylchromen-2-one derivative 35 was found to be consistently active against all the cancer cell lines and inhibited the cell proliferation of SK-OV-3, CCRF-CEM, and MCF-7 by 63%, 50%, and 43%, respectively, at a concentration of 50 μmol/L after 72 h of incubation. This compound also exhibited the highest Src kinase inhibition (IC50 = 14.5 μmol/L). Structure−activity relationship studies provided insights for designing the next generation of chromen-2-one − chalcone hybrid prototypes and the development of new leads as anticancer agents and (or) Src kinase inhibitors.

Biochemical and cellular effects of c-Src kinase-selective pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors

2000 ◽  
Vol 60 (7) ◽  
pp. 885-898 ◽  
Author(s):  
Alan J Kraker ◽  
Brian G Hartl ◽  
Aneesa M Amar ◽  
Mark R Barvian ◽  
H.D.Hollis Showalter ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Src Kinase ◽  
Cellular Effects

New Frontiers in Mucositis

2012 ◽  
pp. 545-551 ◽  
Author(s):  
Douglas E. Peterson ◽  
Dorothy M. Keefe ◽  
Stephen T. Sonis
Keyword(s):  
Kinase Inhibitors ◽  
Management Strategies ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Therapeutics ◽  
Mtor Inhibitors ◽  
Mucosal Injury ◽  
Mucosal Damage ◽  
Nucleotide Polymorphisms ◽  
Oncology Patient ◽  
Novel Technologies

Overview: Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.

scholarly journals Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

2013 ◽  
Vol 23 (11) ◽  
pp. 3230-3234 ◽  
Author(s):  
Amir Nasrolahi Shirazi ◽  
Rakesh Kumar Tiwari ◽  
Alex Brown ◽  
Dindyal Mandal ◽  
Gongqin Sun ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Kinase Inhibitors ◽  
Src Kinase
Sign in / Sign up

Export Citation Format

Share Document