Src kinase inhibitors. Medical search. Frequent questions

Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. (rcsb.org)
The nonreceptor tyrosine kinase Lyn (lck/yes-related novel tyrosine kinase) is widely expressed, and the predominant Src family member present in B cells. (rndsystems.com)
Thus, emerging therapies, including cathepsin K, matrix metalloproteinase, or nonreceptor tyrosine kinase Src inhibitors, are being introduced for prevention and treatment of osteoporosis and cancer bone metastasis. (hindawi.com)
Exhibits selectivity for Fgr and Lyn over other Src family kinases and other nonreceptor and receptor tyrosine kinases. (tocris.com)

and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
Two patients with truncating mutations had liver fibrosis that in one patient resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
The Src family kinase inhibitor dasatinib has been found to effectively block bevacizumab-induced glioma invasion in preclinical models, which led to the hypothesis that combining bevacizumab with dasatinib could increase bevacizumab efficacy in patients with recurrent GBM. (healthpartners.com)
CONCLUSIONS: Despite upregulation of Src signaling in patients with GBM, the combination of bevacizumab with dasatinib did not appear to significantly improve the outcomes of patients with recurrent GBM compared with bevacizumab alone. (healthpartners.com)
When co‑administering dasatinib, a c‑SRC inhibitor, the partial restoration of lenvatinib sensitivity in the JHH‑7_LR cell line was observed. (spandidos-publications.com)
A number of these kinase inhibitors have entered clinical trials, and two products-dasatinib (Sprycel®, Bristol-Myers Squibb) and nilotinib (Tasigna®, Novartis)-have recently been approved by health authorities in the US and Europe for use in patients with CML experiencing imatinib resistance or intolerance. (touchoncology.com)

To continue preclinical research into this approach, Dr. Kratimenos envisions studying the effect of other types of small molecule inhibitors to target the apoptotic cascade, perhaps in multiple doses, eliminating the potential side effects, and determining the best dose and duration of treatment. (news-medical.net)

EGF-stimulated extracellular signal-regulated kinase (ERK) phosphorylation occurred at much lower concentrations of EGF than required to phosphorylate Tyr 845. (aspetjournals.org)
Moreover, the effect of Src family kinase inhibitors on EGF-stimulated ERK phosphorylation was transient, prompting a search for other targets of Src family kinase action. (aspetjournals.org)
Together, these observations demonstrate that one or more Src family kinases act upstream as well as downstream of ErbB1 to promote amphiregulin-dependent autocrine stimulation of NHKs and suggest that autocrine NHK proliferation is more dependent upon ERK activation than upon Tyr 845 phosphorylation. (aspetjournals.org)
c-Src tyrosine kinase plays an important role in signal transduction pathways, where its activity is regulated by phosphorylation of the two tyrosine residues. (intechopen.com)
Looking upstream the kinase cascade, the identity of the kinase (s) that brings about the phosphorylation of the tyrosine residues remains to be elucidated. (umass.edu)
It has been suggested that the non receptor tyrosine kinase Src family is involved in the capacitation associated phosphorylation cascade. (umass.edu)
The capacitation associated tyrosine phosphorylation is greatly reduced in the presence of Src specific inhibitors (SU6656 and SKI606) in vivo. (umass.edu)
Surprisingly, Src inhibitors down regulates the phosphorylation of serine/threonine residues that correlate on earlier events in the capacitation, as assayed by western blot with PKA substrates antibody. (umass.edu)
However, in vitro kinase activity of PKA showed no effect of Src inhibitors in the phosphorylation of the PKA specific substrate, kemptide. (umass.edu)
Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). (uci.edu)
In addition, western blot analysis revealed that ATP-induced phosphorylation of MAPKs in Caco-2 cells was dependent on calcium influx and intracellular calcium release, Src-family tyrosine kinases, and partially dependent on the cAMP/PKA and PKC pathways. (conicet.gov.ar)
The epidermal growth factor receptor (EGFR) specific inhibitor AG1478 decreased ERK1/2, JNK1/2 and p38 MAPK phosphorylation by ATP, suggesting that EGFR transactivation is important for ATP-mediated stimulation of MAPKs in this intestinal cell line. (conicet.gov.ar)
Immunologic and confocal microscopic evidence also suggested a transient but significant stimulation of tyrosine phosphorylation of Cav-1 in β-cells briefly (for 15 min) exposed to IL-1β that was markedly attenuated by three structurally distinct inhibitors of protein tyrosine phosphorylation. (diabetesjournals.org)
Moreover, a comparison of the apo- and inhibitor-bound Lyp structures reveals that the Lyp-specific region S 35 TKYKADK 42 , which harbors a PKC phosphorylation site, could adopt either a loop or helical conformation. (elsevierpure.com)
We demonstrate that Ser-35 phosphorylation impairs Lyp's ability to inactivate the Src family kinases and down-regulate T cell receptor signaling. (elsevierpure.com)

N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. (rcsb.org)
Lenvatinib is an oral multi-kinase inhibitor that inhibits mainly vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptor (PDGFR) α, c-KIT, and RET ( 11 ). (spandidos-publications.com)
This interaction inhibits its tyrosine-kinase activity. (lu.se)

and potent inhibition of NHK proliferation and migration by two Src family kinase inhibitors PP1 and PD173952. (aspetjournals.org)
However, the combination of hypothermia with Src kinase inhibition following hypoxia further attenuated the increased activation of CaM kinase IV, compared with hypothermia alone in the newborn experimental model brain. (news-medical.net)
Die Rolle von Src-Kinasen wurde durch pharmakologische Inhibition analysiert. (uni-wuerzburg.de)
Außerdem konnte demonstriert werden, dass die Inhibition von Src-Kinasen den Anstieg der Endothelpermeabilität signifikant reduziert. (uni-wuerzburg.de)
The present study demonstrated that increased c‑SRC expression was partially associated with HCC resistance to lenvatinib, suggesting that c‑SRC inhibition could reduce the resistance of HCC to lenvatinib. (spandidos-publications.com)
7 Secondary resistance to imatinib is thought to involve acquired evasion of BCR-ABL inhibition by various mechanisms such as mutations in the kinase domain that prevent imatinib binding, or genomic amplification and overexpression of BCR-ABL. (touchoncology.com)

These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. (rcsb.org)
Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. (medscape.org)
Structural and mutational analyses indicate that the inhibitor binds both the active site and a nearby peripheral site unique to Lyp, thereby furnishing a solid foundation upon which inhibitors with therapeutic potency and selectivity can be developed. (elsevierpure.com)

Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors. (cathdb.info)
Crystal Structure Of The Lymphocyte-Specific Kinase Lck In Complex With Staurosporine. (lu.se)

Src family kinases (SFKs) are a group of non-receptor tyrosine kinases whose activity is involved in the regulation of cellular morphology, motility, proliferation and survival. (eurekaselect.com)

Although several lines of evidence also suggest important interactions of ErbB and Src family kinase signaling in normal epithelial cells, little is known about the mechanism of this interaction. (aspetjournals.org)
The combined use of SU 6656 and either PP1 or PP2 may be useful for identifying substrates of Src family members. (nih.gov)
Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN , p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. (nature.com)
A role of Src family kinase members in causing sterile inflammation and human disease is only recently recognized. (nature.com)
Here, we show that the non-receptor Src family tyrosine kinases, SRC64B and SRC42A, are involved in WNT5-mediated signaling through Derailed in the Drosophila embryonic central nervous system. (biologists.com)
This gene is a member of the protein-tyrosine kinase oncogene family. (cancerindex.org)
Using an immunological approach we show that the only Src family member present in mouse sperm extract is Src. (umass.edu)
presents a promising therapy that used inhibitors of the Src family kinases (SFKs) for neuroprotection in a preterm model of HI brain injury ( Qiu et al. ). (frontiersin.org)
The proposed model had success rates of 84% in GSK3b+JNK3 inhibitor generation and 99% in Bcl-2 family inhibitor generation tasks. (bvsalud.org)
Members of the src-family tyrosine kinases that are activated during the transition from G2 PHASE to M PHASE of the CELL CYCLE. (bvsalud.org)
Belongs to the tyr protein kinase family. (lu.se)

Its molecular counterpart, the resultant BCR-ABL fusion gene, encodes a constitutively active form of the ABL tyrosine kinase (TK) that induces malignancy through the activation of multiple signal transduction pathways involved in hematopoietic cell growth and survival. (touchoncology.com)

AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. (rcsb.org)
c-Src (cellular Src), encoded by Src gene, is a non-receptor tyrosine kinase first isolated as the normal cellular homolog to the potent avian sarcoma viral transforming oncogene v-Src [ 4 ]. (intechopen.com)
TL 0259 is a selective and highly potent Fgr and Lyn inhibitor (IC 50 values are 0.03 and 0.1 nM, respectively). (tocris.com)

Computational studies such as receptor-based and/or ligand-based virtual screening, docking, and molecular modeling proved to be a powerful tool for identifying new SFKs inhibitors. (eurekaselect.com)

We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. (rcsb.org)

SRC expression was determined with immunohistochemical staining from pretreatment biopsies (n=152) and residual tumor tissue from the resection specimens (n=163). (jcancer.org)
High SRC expression in pretherapeutic tumor samples significantly correlated with a negative postoperative nodal status (p=0.005). (jcancer.org)
If severe, biologic therapy is used to treat patients with severe Crohn's disease that does not respond to any other types of medication, such as a TNF (tumor necrosis factor) inhibitor which can have secondary effects, and they are not universally effective. (pharmaceuticalintelligence.com)

As a means of control for the activity of Src inhibitors in our system, parallel experiments assaying the activity of PKA both in vivo and in vitro were realized. (umass.edu)

Using a panel of kinase inhibitors, we found ALK inhibitor AZD3463 selectively inhibited the activation and downstream signaling of FLT3-ITD and did not affect the wild-type FLT3 (FLT3-WT). (lu.se)

We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. (nih.gov)
Third, consideration is provided of new, first-in-class, selective inhibitors of NOX-1. (nih.gov)

In oxygen deprivation of the brain, the pathways leading to cell death are over-activated, including the nuclear enzyme CaM kinase IV. (news-medical.net)
Bosutinib is an oral, once-daily, kinase inhibitor, which limits cancer cell growth by inhibiting the Abl and Src signaling pathways. (aol.com)
Using Ingenuity Pathway Analysis bioinformatics software, it was revealed that the activity of multiple signaling pathways varied alongside the changes in expression of these proteins, and c‑SRC was identified as a protein involved in a number of these signaling pathways, with its activity varying markedly upon the acquisition of resistance. (spandidos-publications.com)
Nearly 60% of genetic alterations have been found in AML patients involve in signaling pathways including signaling of tyrosine kinase receptor FLT3. (lu.se)

One such targeted therapy, imatinib mesylate (Gleevec®, Novartis), was found to be a relatively specific inhibitor of the BCR-ABL TK and effective in blocking the molecular signals contributing to the CML phenotype. (touchoncology.com)
Imatinib binds the ABL domain at the ATP-binding site and traps the protein in an inactive conformation to inhibit the kinase activity. (touchoncology.com)
Knowledge of the molecular mechanisms behind imatinib resistance has led to the development of second-generation ABL kinase inhibitors. (touchoncology.com)
These second-generation agents have significantly higher potency compared with imatinib and activity against most imatinib-resistant BCR-ABL kinase domain mutants. (touchoncology.com)

Pharmacological response data for targeted inhibitors of SRC, WNT, GSK3b, aurora kinase, PI3 kinase, and mTOR, showed significant differences in sensitivity across cell lines assigned to different subtypes. (tudelft.nl)

Protein Kinases Promising Targets for Anticancer Drug Researc. (intechopen.com)

The ErbB inhibitor PD158780 and the mitogen-activated protein kinase kinase inhibitor U0126 also markedly inhibited NHK proliferation, migration, and amphiregulin production. (aspetjournals.org)
BACKGROUND: Src signaling is markedly upregulated in patients with invasive glioblastoma (GBM) after the administration of bevacizumab. (healthpartners.com)

Aqlan, Synthesis, ADMET and docking studies of novel pyrazoles incorporating coumarin moiety as tyrosine kinase (Src) inhibitors, Biointerface Res. (dntb.gov.ua)

Although several FLT3 inhibitors have been developed and showed promising results in clinical trials, many patients develop drug resistance shortly after treatment starts and display poor outcome. (lu.se)

In terms of the disease control rate (complete response + partial response + stable disease ratio), response rate (complete response + partial response ratio), median progression-free survival, and median time to progression, lenvatinib shows significantly better results compared with sorafenib, another oral multi-kinase inhibitor (75.5 vs. 60.5%, 24.1 vs. 9.2%, 7.4 vs. 3.7 months, 8.9 vs. 3.7 months, respectively) ( 7 ). (spandidos-publications.com)
We generated 1000 chemical formulas using the chemical properties of sorafenib and the three target kinases of sorafenib. (bvsalud.org)

The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase. (jcancer.org)

c-Src potentiates proliferation, survival, and invasiveness in response to epidermal growth factor (EGF) in human mammary carcinoma cells. (aspetjournals.org)
We characterize the role of increased Lyn kinase activity in neutrophils, endothelial cells and lesional liver biopsies and utilized an iPSC-derived endothelial cell platform for disease modeling of neutrophilic vasculitis and to screen and evaluate drug efficacy. (nature.com)
Second, regulation of NOX-1 in beta cells involves feed-forward control linked to elevated ROS and Src-kinase activation. (nih.gov)
8000 Bahía Blanca, Argentina In the present work, we examined the role of ATP in the activation of the MAP kinases (MAPKs) ERK1/2, JNK1/2 and p38 and their involvement in the modulation of transcription factors and proliferation of human colon cancer Caco-2 cells. (conicet.gov.ar)
These findings provide new molecular basis for further understanding the mechanisms involved in ATP functions, as a signal transducer and activator of MAP kinase cascades, in Caco-2 cells derived from human colon adenocarcinoma. (conicet.gov.ar)

The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (cancerindex.org)
Binds to phosphatidylinositol 3'-kinase (PI3k) from T lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of khdrbs1/p70 through its SH2 domain. (lu.se)

An aberrant activation and expression of these kinases contribute to the pathogenesis and progression of a broad range of diseases, such as a large number of solid tumors, various hematological malignancies and some neuronal pathologies. (eurekaselect.com)
In hypoxia-ischemia, CaM kinase is over-activated, but hypothermia has been shown to decrease this enzyme's activation. (news-medical.net)
We theorized that a Src kinase inhibitor, in addition to hypothermia, would further attenuate the activation of CaM kinase IV and that the result might be less brain damage,' explains Panagiotis Kratimenos, M.D., Ph.D., the study's lead author, and a specialist in neonatology and neonatal neurocritical care at Children's National. (news-medical.net)
The authors conclude that hypothermia alone attenuated the over-activation of CaM kinase IV and improved neuropathology after hypoxia. (news-medical.net)
In contrast to the case of many kinases, we have found that the activation loop of FLT3 is not essential for its activation. (lu.se)

c-Src tyrosine kinase consists of the N-terminal unique region, the Src homology 3 (SH3), SH2, linker, kinase domain, and the regulatory C-terminal tail. (intechopen.com)
The experimental models were given standard cooling therapy (therapeutic hypothermia) alone and in combination with a selective Src kinase inhibitor, PP2, that blocks a regulatory enzyme of apoptosis (cell death), which intensifies as a result of hypoxia-ischemia. (news-medical.net)

Little is known about how the kinase activity-deficient RYKs transduce Wnt signals. (biologists.com)
Derailed and SRC64B form a complex, which contains catalytically active SRC64B, the formation or stability of which requires SRC64B kinase activity. (biologists.com)
The research team assessed neuropathology, adenosine triphosphate and phosphocreatine concentrations as well as CaM kinase IV activity. (news-medical.net)
The CaM kinase IV activity in cerebral tissue was 2,002 (plus or minus 729) with normal oxygen levels and in normal temperatures, 4,104 (plus or minus 542) in hypoxia with hypothermia treatment, and 2,165 (plus or minus 415) in hypoxia with hypothermia treatment combined with PP2 administration. (news-medical.net)
Taddei S (2016): "Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity. (antikoerper-online.de)

the company also just ended codevelopment of I-Mab's lemzoparlimab, another CD47 inhibitor, besides recently dropping Harpoon Therapeutics' anti-BCMA trispecific T-cell engager, HPN217. (aacrjournals.org)

Bisphosphonates and denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, delay time to first skeletal related event. (hindawi.com)

Efficacy of BRAF/MEK inhibitor combination highlights need for routine biomarker testing in pediatric brain cancer care. (aacrjournals.org)

Here, we report the identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with excellent cellular efficacy. (elsevierpure.com)

Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. (nih.gov)

The mammalian orthologs of Derailed and SRC64B also form complexes, suggesting that Src roles in RYK signaling are conserved. (biologists.com)

Anatomy15

Organisms7

Diseases3

Chemicals and Drugs172

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes43

Disciplines and Occupations1

Information Science3

Nonreceptor4

Dasatinib6

Small Molecule Inhibitors1

Phosphorylation15

Inhibits3

Inhibition6

Selectivity3

Lymphocyte-specific kinase2

Receptor tyrosin1

Family11

Signal Transduction1

Potent3

SFKs1

Enzymes1

Tumor3

Vitro1

Selectively inhibited1

Selective inhibitors2

Pathways4

Imatinib4

GSK3b1

Targets1

Markedly2

Pyrazoles1

Clinical1

Sorafenib2

Oncogene1

Cells5

Phosphatidylinositol2

Activation5

Regulatory2

Activity5

Therapeutics1

Activator1

Biomarker1

Cellular1

Substrates1

Roles1