Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A new challenging and promising era of tyrosine kinase inhibitors.

ABSTRACT: Protein kinases are key regulators that govern complex cellular processes. Dysregulation of kinase signaling is associated in many human diseases, particularly cancers and developmental and metabolic disorders. Tyrosine kinase inhibitors have achieved great success in molecular targeted therapies for cancer and now is expanding to other therapeutic areas. The onset of drug resistance to prolonged TKI treatment brings new challenges in TKI drug development. The deep understanding of disease pathologies related to TKs and drug resistance mechanisms will generate new waves for seeking highly selective, potent, and safe TKIs.

SUBMITTER: Cui JJ

PROVIDER: S-EPMC4027765 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A new challenging and promising era of tyrosine kinase inhibitors.

Cui J Jean JJ

ACS medicinal chemistry letters 20140306 4

Protein kinases are key regulators that govern complex cellular processes. Dysregulation of kinase signaling is associated in many human diseases, particularly cancers and developmental and metabolic disorders. Tyrosine kinase inhibitors have achieved great success in molecular targeted therapies for cancer and now is expanding to other therapeutic areas. The onset of drug resistance to prolonged TKI treatment brings new challenges in TKI drug development. The deep understanding of disease patho ...[more]

PMID: 24900820

Similar Datasets

Bruton's Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy.

Project description:B cells play a central role in the pathogenesis of multiple sclerosis (MS), as demonstrated through the success of various B cell-depleting monoclonal antibodies. Bruton's tyrosine kinase (BTK) is a critical molecule in intracellular signaling from the receptor of B cells and receptors expressed in the cells of the innate immune system. BTK inhibitors may be a non-cell-depleting alternative to B cell modulation. In this review, the structure, signaling, and roles of BTK are reviewed among the different inhibitors assayed in animal models of MS and clinical trials.

| S-EPMC8534278 | biostudies-literature

Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas.

Project description:Constitutive or aberrant signalling of the B cell receptor signalling cascade has been implicated in the propagation and maintenance of a variety of B cell malignancies. Small molecule inhibitors of Bruton tyrosine kinase (BTK), a protein early in this cascade and specifically expressed in B cells, have emerged as a new class of targeted agents. There are several BTK inhibitors, including ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical and/or clinical development of which ibrutinib is currently in phase III trials. Recent clinical data suggest significant activity of ibrutinib as a first in class oral inhibitor of BTK. This review provides an overview of ongoing clinical studies of BTK inhibitors.

| S-EPMC4444436 | biostudies-literature

Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma.

Project description:Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman's breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare.

| S-EPMC8002158 | biostudies-literature

Rational Drug Design of Axl Tyrosine Kinase Type I Inhibitors as Promising Candidates Against Cancer.

Project description:The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.

| S-EPMC7010640 | biostudies-literature

The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.

Project description:Imatinib mesylate was the first tyrosine kinase inhibitor (TKI) approved for the management of chronic myeloid leukemia. Imatinib produces acceptable responses in approximately 60% of patients, with approximately 20% discontinuing therapy because of intolerance and approximately 20% developing drug resistance. The advent of newer TKIs, such as nilotinib, dasatinib, bosutinib, and ponatinib, has provided multiple options for patients. These agents are more potent, have unique adverse effect profiles, and are more likely to achieve relevant milestones, such as early molecular responses (3-6 months) and optimal molecular responses (12 months). The acquisition of BCR-ABL kinase domain mutations is also reportedly lower with these drugs. Thus far, none of the randomized phase III clinical trials have shown a clinically significant survival difference between frontline imatinib versus newer TKIs. Cost and safety issues with the newer TKIs, such as vascular disease with nilotinib and ponatinib and pulmonary hypertension with dasatinib, have dampened the enthusiasm of using these drugs as frontline options. While the utility of new TKIs in the setting of imatinib failure or intolerance is clear, their use as frontline agents should factor in the age of the patient, additional comorbidities, risk stratification (Sokal score), and cost. Combination therapies and newer agents with potential to eradicate quiescent chronic myeloid leukemia stem cells offers future hope.

| S-EPMC4742366 | biostudies-literature

Survival of mantle cell lymphoma in the era of Bruton tyrosine kinase inhibitors: a population-based analysis.

Project description: Not available

| S-EPMC9198937 | biostudies-literature

Nanomedicine of tyrosine kinase inhibitors.

Project description:Recent progress in nanomedicine and targeted therapy brings new breeze into the field of therapeutic applications of tyrosine kinase inhibitors (TKIs). These drugs are known for many side effects due to non-targeted mechanism of action that negatively impact quality of patients' lives or that are responsible for failure of the drugs in clinical trials. Some nanocarrier properties provide improvement of drug efficacy, reduce the incidence of adverse events, enhance drug bioavailability, helps to overcome the blood-brain barrier, increase drug stability or allow for specific delivery of TKIs to the diseased cells. Moreover, nanotechnology can bring new perspectives into combination therapy, which can be highly efficient in connection with TKIs. Lastly, nanotechnology in combination with TKIs can be utilized in the field of theranostics, i.e. for simultaneous therapeutic and diagnostic purposes. The review provides a comprehensive overview of advantages and future prospects of conjunction of nanotransporters with TKIs as a highly promising approach to anticancer therapy.

| S-EPMC7778595 | biostudies-literature

Tyrosine kinase inhibitors and interferon.

Project description:The use of interferon-a (INF) in chronic myeloid leukemia, when it started in the 80s, was considered as a breakthrough in the therapy of this disease; INF administered alone or in combination with aracytin was the standard choice for treatment for Chronic Myeloid Leukemia (CML) patients unfit for bone marrow transplantation. With the appearance of the first Tyrosine Kinase Inhibitor (TKI) (imatinib) and based on the results of the pivotal IRIS trial, imatinib monotherapy was the new treatment of choice for CML, according to the ELN recommendations. The possibility of combining INF with imatinib, for obtaining better therapeutic responses in CML patients has been already tested and reported. The current challenge is the combined use of second generation TKIs with pegylated -IFN, in order to minimize failures to therapy and increase the number of CML patients with deep molecular responses, who may be able to discontinue lifelong treatment.

| S-EPMC3894836 | biostudies-literature

Paxlovid: A promising drug for the challenging treatment of SARS-COV-2 in the pandemic era.

Project description:Coronavirus infection is a pandemic threat and the most dangerous disease of the 21st century. Despite the rigorous exertion of world-class researchers, there is no perfect cure for it. It has been seen in presently available studies that Paxlovid prevents the progression of diseases and reduces severity in patients tremendously who are at high risk of hospitalization and death. It is a safe oral antiviral drug and has the potential to treat infections from multiple corona variants including omicron which affects humans. Paxlovid is comparatively less expensive than other available effective medicines. Consequently, it reduces hospitalization and death and helps to plummet the economic burden on patients and the health-care system globally. This medicine is still under investigation, and numerous clinical trials are still underway. Its potential side effects are minor and well tolerated by research study participants. Studies show its benefits outweigh the risk, and it is an effective and good alternative for the treatment of coronavirus disease.

| S-EPMC10043822 | biostudies-literature

Histologic transformation induced by EGFR tyrosine kinase inhibitors

Project description:Although tyrosine kinase inhibitors (TKIs) targeting Epidermal Growth Factor Receptor (EGFR) activating mutations have significantly improved outcomes in EGFR-mutant non-small cell lung cancer, resistance inevitably develops. Despite the heterogeneity of resistance mechanisms, many induce activation of MAPK signaling in the presence of EGFR-TKIs. ARAF gene amplification is identified as one such mechanism that activates MAPK signaling by directly interacting with RAS, yet its clinicopathologic characteristics remain poorly understood. We characterized five cases with ARAF amplification resistant to first- or second-generation EGFR-TKIs and screened an additional 48 re-biopsied specimens following resistance to Osimertinib. Among Osimertinib-resistant tumors, we identified four cases with ARAF amplification. Overall, these nine ARAF-amplified resistant tumors retained their original founder EGFR mutation and lacked secondary alterations. Furthermore, we identified two cases showing histologic transformation from lung adenocarcinoma to small cell lung cancer (SCLC). SCLC can be classified into four subtypes defined by transcriptional signatures driven by specific transcription factors. To estimate the subtypes of these resistant tumors, RNA sequencing analysis was performed in paired samples before and after treatment with EGFR-TKIs.

2024-10-30 | GSE274293 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data