 |
Companies | Products |
|
|
Products | |
Diseases | |
Trials |  |
News |  |
| 12345678» |
- | Journal: Sialylation on vesicular integrin ?1 determined endocytic entry of small extracellular vesicles into recipient cells. (Pubmed Central) - Apr 6, 2024
Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells.
- || Review, Journal: The Role of Snake Venom Disintegrins in Angiogenesis. (Pubmed Central) - Mar 31, 2024
The potential applications of SVD in diseases related to angiogenesis, such as cancer, ocular diseases, tissue regeneration, wound healing, and cardiovascular diseases, are also discussed. Overall, SVDs are promising potential therapeutics, and further advances in this field could lead to innovative treatments for diseases related to angiogenesis.
- DATK32 / Biora Therap, Entyvio (vedolizumab) / Takeda
REAL-TIME INHIBITION OF INTEGRIN ?4?7 BY A SMALL MOLECULE INHIBITOR IMPAIRS B LYMPHOCYTE ADHESION IN MURINE PEYER (Hall A) - Mar 14, 2024 - Abstract #DDW2024DDW_7345;
Vedolizumab, an anti-?4?7 antibody approved for the treatment of inflammatory bowel diseases (IBD), blocks leukocyte homing to the gut...B cell migration within vessels was recorded for up to 60 minutes following the intravenous administration of MT-108 or DATK32, an anti-?4?7 antibody...These results are consistent with previous murine studies showing decellularization in the PP in response to ?4?7 blockade. Thus, a small molecule ?4?7 antagonist can rapidly impact cell homing to gut-associated lymphoid tissues replicating the speed of onset and efficacy of an antibody.
- | Journal: Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin ?2?1. (Pubmed Central) - Mar 8, 2024
Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.
- Phosphorylated focal adhesion kinase by mild reduction of cell surface proteins inhibits integrin ?5?1-dependent patient- derived cancer cell migration and invasion (Section 7) - Mar 5, 2024 - Abstract #AACR2024AACR_8588;
Additionally, when these cells were cultured on stiff PAAm hydrogels mimicking the tumor microenvironment, the cells exhibited accelerated cell migration behaviors, compared to cells on soft hydrogels. These results highlight the synergetic contributions of feeder cells and Rho kinase inhibitor to support long-term self-renewal of tongue cancer patient-derived epithelial cells.
- | Journal: Activation of ductal progenitor-like cells from adult human pancreas requires extracellular matrix protein signaling. (Pubmed Central) - Mar 4, 2024
Inhibition of integrin ?1?1, a major collagen IV receptor, negates collagen IV- and Matrigel-stimulated effects. These results demonstrate that collagen IV is a key ECM protein that stimulates the expansion and polarization of human ductal progenitor-like and ductal non-progenitor cells via integrin ?1?1 receptor signaling.
- | aspirin / Generic mfg.
Preclinical, Journal: Antiplatelet and Antithrombotic Activities of Lespedeza cuneata via Pharmacological Inhibition of Integrin ?IIb?3, MAPK, and PI3K/AKT Pathways and FeCl3-Induced Murine Thrombosis. (Pubmed Central) - Feb 19, 2024
Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400?mg/kg and aspirin 100?mg/kg for 7?days, and tail bleeding and FeCl3-induced murine thrombus model were performed...In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects.
- | Journal, IO biomarker: Identifying the prognosis implication, immunotherapy response prediction value, and potential targeted compound inhibitors of integrin subunit ?3 (ITGA3) in human cancers. (Pubmed Central) - Jan 31, 2024
ITGA3 may participate in shaping and regulating the tumor microenvironment to affect the tumor immune response, which was a promising immunotherapy response predictive biomarker and potential therapeutic target to work synergistically with cancer immunotherapy to boost the response and efficacy. Finally, potential targeted compound inhibitors and sensitive drugs were screened using databases ConnectivityMap (CMap) and CellMiner, and AutoDock Tools was used for molecular docking.
- | Cilcane (cilengitide) / Iceni Pharma
Journal: Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage. (Pubmed Central) - Dec 18, 2023
Finally, potential targeted compound inhibitors and sensitive drugs were screened using databases ConnectivityMap (CMap) and CellMiner, and AutoDock Tools was used for molecular docking. Integrin ?v?5 plays an important role for irisin in modulating the protective effect during hemorrhage.
- | Journal: Inhibition of cancer cell?platelet adhesion as a promising therapeutic target for preventing peritoneal dissemination of gastric cancer. (Pubmed Central) - Nov 29, 2023
Furthermore, in vivo analyses demonstrated that the platelet-induced enhancement of peritoneal dissemination was significantly suppressed by the coadministration of anti-GPVI antibody and galectin-3 inhibitor, and was nearly eliminated by the combined treatment. The inhibition of adhesion resulting from GPVI-galectin-3 interaction may be a promising therapeutic strategy for preventing peritoneal dissemination in patients with GC.
- | Journal: Targeting NADPH Oxidase and Integrin ?5?1 to Inhibit Neutrophil Extracellular Traps-Mediated Metastasis in Colorectal Cancer. (Pubmed Central) - Nov 18, 2023
The combination of NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) and integrin ?5?1 inhibitor ATN-161 (Ac-PHSCN-NH2) effectively suppresses tumor progression in vivo. Our work reveals the mechanistic link between NETs and tumor progression and suggests a combination therapy against NETs-mediated metastasis for CRC.
- | Journal: Integrin-based adhesions promote cell-cell junction and cytoskeletal remodelling to drive embryonic wound healing. (Pubmed Central) - Nov 16, 2023
Additionally, disrupting integrins caused a defect in E-cadherin reinforcement at tricellular junctions along the wound edge, suggesting crosstalk between integrin-based and cadherin-based adhesions. Our results show that cell-ECM adhesion contributes to embryonic wound repair and reveal an interplay between cell-cell and cell-ECM adhesion in the collective cell movements that drive rapid wound healing.
- Impact of Recombinant Factor VIII and Platelet Interaction on Platelet Functionality and Hemophilia a Treatment (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1640;
The increased binding of simoctocog alfa was associated with a phenotypic shift in platelets as evidenced by increased exposure of PS on the platelet membranes. The binding of simoctocog alfa to platelets was disrupted when integrin aIIb
- | Journal: Inhibition of integrin binding to ligand arg-gly-asp motif induces AKT-mediated cellular senescence in hepatic stellate cells. (Pubmed Central) - Oct 30, 2023
The binding of simoctocog alfa to platelets was disrupted when integrin aIIb Pharmacological inhibition of RGD-mediated integrin binding induces senescence in activated HSCs.
- | Journal: Osteosarocma progression in biomimetic matrix with different stiffness: Insights from a three-dimensional printed gelatin methacrylamide hydrogel. (Pubmed Central) - Aug 19, 2023
The transplantation of 3D printed models in nude mice showed that cells encapsulated in the softer hydrogel were more likely to form subcutaneous tumors. These results suggest that matrix stiffness plays an important role in the development of osteosarcoma in a 3D environment and that inhibition of integrin ?5 could block the signal transduction of matrix stiffness.
- | Journal: Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth. (Pubmed Central) - Aug 9, 2023
This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer.
- | Journal: Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition via p-FAK/p-paxillin/YAP signaling. (Pubmed Central) - Aug 2, 2023
CAF sEV-associated integrin ?2?1 mediated the binding of CAF sEVs to collagen I, and blocking integrin ?2?1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
- | Preclinical, Journal: Transglutaminase 2 Facilitates Murine Wound Healing in a Strain-Dependent Manner. (Pubmed Central) - Aug 2, 2023
Rho-family GTPase activation, central to cytoskeletal organization, was altered in 129 TG2 MEFs, with delayed RhoA and earlier Rac1 activation than in TG2 MEFs. These findings indicate that the rate of wound healing is different between 129 and B6 mouse strains, correlating with TG2 abundance, and although not essential for wound healing, TG2 facilitates integrin- and syndecan-mediated RhoA- and Rac1-activation in fibroblasts to promote efficient wound contraction.
- || Review, Journal: Targeting integrin ?5?1 in urological tumors: opportunities and challenges. (Pubmed Central) - Jul 24, 2023
In addition, the clinical applications of integrin ?5?1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin ?5?1 as a potential target for treatment is examined, with new ideas for future research being proposed.
- | MK-2206 / Merck (MSD)
Journal: Microfibril-associated glycoprotein-2 promotes fracture healing via integrin ?v?3/PTK2/AKT signaling. (Pubmed Central) - Jul 24, 2023
Last but not least, the possibility of integrin ?5?1 as a potential target for treatment is examined, with new ideas for future research being proposed. In
- | Journal: Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchin Strongylocentrotus purpuratus. (Pubmed Central) - Jun 16, 2023
In contrast to gastrula stages, the acceleration of skeletogenesis by thyroxine in older larvae is not fully inhibited by competitive ligands or inhibitors of the integrin membrane receptor pathway, suggesting that THs likely activate multiple pathways. Our data confirms a signaling function of THs in sea urchin development and suggests that both genomic and non-genomic mechanisms play a role, with genomic signaling being more prominent during later stages of larval development.
- CS585 is a novel and highly selective IP receptor agonist for prevention of thrombosis (Room:710A) - May 18, 2023 - Abstract #ISTH2023ISTH_2231;
CS585 also functioned in human whole blood ex vivo and in prevention of both small and large vessel thrombosis in mouse models. Finally, we demonstrate that CS585 does not perturb coagulation or increase the risk for bleeding Conclusion(s): We have developed a novel small molecule agonist that is selective for the prostacyclin receptor, stable in human and mouse blood, is effective in prevention of unwanted platelet-mediated thrombosis and doesn't alter hemostasis.
- bexotegrast (PLN-74809) / Pliant Therapeutics
INTEGRIS-PSC phase 2a study: evaluating the safety, tolerability, and pharmacokinetics of bexotegrast (PLN-74809) in participants with primary sclerosing cholangitis (Poster Area) - Apr 12, 2023 - Abstract #EASLILC2023EASL_ILC_519;
P2a
The INTEGRIS-PSC phase 2a study evaluating the safety, tolerability, and pharmacokinetics of bexotegrast in participants with primary sclerosing cholangitis continues without modification by the Data Safety Monitoring board. Results from this study are expected in 3Q2023.
- || Review, Journal: Structure, signal transduction, activation, and inhibition of integrin ?IIb?3. (Pubmed Central) - Feb 15, 2023
This review describes the structure and signal transduction of ?IIb?3, summarizes the molecules that directly or indirectly affect integrin ?IIb?3 activation, and discusses some novel anti?IIb?3 drugs. This will advance our understanding of the activation of ?IIb?3 and its essential role in platelet function and tumor development.
- | Journal: Stiff substrates inhibit collagen accumulation via integrin α2β1, FAK and Src kinases in human atrial fibroblast and myofibroblast cultures derived from patients with aortal stenosis. (Pubmed Central) - Jan 26, 2023
The elasticity of the cellular environment exerts a regulatory influence on both synthesis and breakdown of collagen. Integrin α2β1, FAK and Src kinase activity participates in signal transmission, which may influence fibrosis in the atria of the human heart.
- | Journal: Basal cell adhesion molecule promotes metastasis-associated processes in ovarian cancer. (Pubmed Central) - Jan 18, 2023
While BCAM appears to have tumour-suppressive effects on single cells, it promotes the dispersion of OC cell spheroids by regulating LAMA5-integrin-β1-dependent compaction and thereby facilitating invasion of metastatic target sites. As peritoneal dissemination is majorly mediated by spheroids, these findings offer an explanation for the association of BCAM with a poor clinical outcome of OC, suggesting novel therapeutic options.
- | Journal: Mammalian STE20-like kinase-1/2 are activated in human platelets stimulated by collagen or thrombin and play a vital role in collagen-activated platelets. (Pubmed Central) - Dec 12, 2022
As peritoneal dissemination is majorly mediated by spheroids, these findings offer an explanation for the association of BCAM with a poor clinical outcome of OC, suggesting novel therapeutic options. This study is the first to demonstrate that MST1/2 play vital roles in human platelets and contributes to collagen-induced platelet activation and aggregation.
- | Journal: Integrinβ1/FAK/ERK signalling pathway is essential for Chinese mitten crab Eriocheir sinensis hemocyte survival. (Pubmed Central) - Dec 6, 2022
We further found that the attenuation of ERK phosphorylation enhanced the level of Caspase-3 expression. Together, these findings suggest that integrinβ1 activates the FAK/ERK signaling cascade and is involved in the survival of Chinese mitten crab hemocytes.
- | Journal: Elevated Serum Amyloid A Levels Contribute to Increased Platelet Adhesion in COVID-19 Patients. (Pubmed Central) - Nov 27, 2022
Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.
- || methotrexate / Generic mfg., azathioprine / Generic mfg.
Clinical, Journal: Antibody response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease - results of a single-center cohort study in a tertiary hospital in Germany. (Pubmed Central) - Nov 19, 2022
Concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on seroconversion. Further evaluation of antibody titers over time is mandatory to detect early the need for re-vaccination in these patients.
- | Journal: Integrin β1 transduces the signal for LY6D-induced macropinocytosis and mediates senescence-inducing stress-evoked vacuole formation via FAK. (Pubmed Central) - Nov 18, 2022
Inhibition of integrin β1 impaired LY6D-induced macropinocytosis, and integrin β1 activated SFK through focal adhesion kinase to mediate macropinocytosis. These results indicate that integrin β1 is a crucial mediator of the LY6D-induced vacuole formation in senescent cells.
- || Review, Journal: Integrins in cardiac fibrosis. (Pubmed Central) - Nov 15, 2022
The profile and role of integrins in cardiac fibrosis may be dependent on the underlying pathologic condition. Considering their cell surface localization and the availability of small molecule inhibitors, integrins may be attractive therapeutic targets for patients with heart failure associated with prominent fibrotic remodeling.
- OS2966 / Enochian BioSciences
The Role of Integrin Beta-1 in the Chemoresistance of Acute Myeloid Leukemia (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_5767;
ITGB1 inhibition with OS2966 combined with chemotherapy significantly decreases cell viability of AML cell lines in vitro and prolongs survival of xenograft mice in vivo. Our findings will allow for better understanding of the role of ITGB1 in drug resistance of AML and of ITGB1 as a preclinical target in AML.
- | Journal: Anti-GPVI nanobody blocks collagen- and atherosclerotic plaque-induced GPVI clustering, signaling and thrombus formation. (Pubmed Central) - Oct 26, 2022
This work emphasizes the critical difference in GPVI-mediated platelet activation by plaque and collagen; it highlights the importance of GPVI clustering for downstream signaling and thrombus formation. Labeled Nb28 is a novel tool for providing mechanistic insight into this process and the data suggest Nb2 warrants further investigation as a potential anti-thrombotic agent.
- | Journal: Defective Desmosomal Adhesion Causes Arrhythmogenic Cardiomyopathy by Involving an Integrin-αVβ6/TGF-β Signaling Cascade. (Pubmed Central) - Oct 22, 2022
A pilot in vivo drug test revealed this pathway as a promising target to ameliorate fibrosis. This highlights the value of this model to discern mechanisms of cardiac fibrosis and to identify and test novel treatment options for ACM.
- dasatinib / Generic mfg.
Serum IgA1-IgG-Containing Immune Complexes From Patients With IgA Nephropathy Activate Cultured Human Mesangial Cells and Associate With Cellular Integrin β1 (Exhibit Hall, Orange County Convention Center, West Building) - Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_3041;
Inhibitors of integrin α1β1 (obtustatin) and α5β1 (Arg-Gly-Asp peptide; RGD), and protein-tyrosine kinases (dasatinib) and Sheng Ping (a herbal medicine for treatment of patients with IgAN in China), were tested for their inhibitory effects...Conclusion Thus, IgA1-IgG immune complexes associated with mesangial cells and this process was, at least in part, mediated by integrin α1β1 and α5β1 and involved activation of multiple signaling pathways. A better understanding of the pathways activated by IgA1-IgG immune complexes may provide new therapeutic approaches for IgAN.
- OS2966 / Enochian BioSciences
Trial Update -Results of a phase I window of opportunity trial evaluating a first-in-class CD29 inhibitor, OS2966, in recurrent high-grade glioma (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_483;
A better understanding of the pathways activated by IgA1-IgG immune complexes may provide new therapeutic approaches for IgAN. Initial data demonstrate the safety and feasibility of direct intracranial delivery of OS2966.
- | Journal: A general chemical principle for creating closure-stabilizing integrin inhibitors. (Pubmed Central) - Sep 20, 2022
Expulsion of this water is a requisite for transition to the open conformation. This change in metal coordination is general to integrins, suggesting broad applicability of the drug-design principle to the integrin family, as validated with a distantly related integrin, α4β1.
- | Journal: Lumican, an Exerkine, Protects against Skeletal Muscle Loss. (Pubmed Central) - Sep 18, 2022
Both intravenous and intramuscular lumican treatment significantly increased muscle CSA. Our in vitro and in vivo experiments indicate that lumican is a muscle-secreted exerkine that affords protection against muscle loss by activating p38 MAPK via integrin receptors.
- | cinaciguat (BAY 58-2667) / Bayer
Journal: Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets. (Pubmed Central) - Sep 10, 2022
Furthermore, pre-incubation with Ceefourin-1 significantly increased PGE1- and cinaciguat-induced vasodilatorstimulated phosphoprotein (VASP) phosphorylation, indicating increased cytosolic cAMP as well as cGMP concentrations, respectively...In conclusion, selective MRP4 inhibition causes reduced platelet adhesion and thrombus formation under flow conditions. This finding is mechanistically supported by inhibition of integrin αIIbβ3 activation, elevated VASP phosphorylation and reduced calcium influx, based on inhibited cyclic nucleotide and thromboxane transport as well as possible further mechanisms.
- | Journal: Mechanical communication-associated cell directional migration and branching connections mediated by calcium channels, integrin β1, and N-cadherin. (Pubmed Central) - Sep 3, 2022
Inhibition of integrin β1 with siRNA knockdown reduced cell directional migration and branching assembly, whereas inhibition of cell junctional N-cadherin with siRNA had little effect on distant attractions but blocked branching assembly. Our work demonstrated that the endoplasmic reticulum calcium channels and integrin are mechanosensing signals for cell mechanical communications regulated by actomyosin activity, while N-cadherin is responsible for traction force-induced cell stable connections in the assembly.
- | Journal: CD146 interaction with integrin β1 activates LATS1-YAP signaling and induces radiation-resistance in breast cancer cells. (Pubmed Central) - Aug 31, 2022
This study identifies a unique function of CD146 implicates with integrin β1 and YAP signaling, contributing to radiation resistance. Targeted therapy against CD146 or inhibition of integrin β1 is a potential strategy to overcome radiotherapeutic resistance of breast cancer.
- | Preclinical, Journal: Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo. (Pubmed Central) - Aug 24, 2022
Targeted therapy against CD146 or inhibition of integrin β1 is a potential strategy to overcome radiotherapeutic resistance of breast cancer. Glycolytic enzymes are involved in stiffness-induced angiocrine signaling in LSECs and represent druggable targets in early liver disease.
- | Journal: αvβ1 integrin is enriched in extracellular vesicles of metastatic breast cancer cells: A mechanism mediated by galectin-3. (Pubmed Central) - Aug 6, 2022
EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV-bound integrin αvβ1 with breast cancer metastasis and provide additional insights into the export of integrin αvβ1 into EVs in the context of metastasis.
- Pharmacological inhibition of Integrin a5b1 improves insulin sensitivity in H9C2 cells and cardiac performance in obese mice (Nobel Hall) - Jul 9, 2022 - Abstract #EASD2022EASD_509;
Pharmacological inhibition of integrin α5β1 improved insulin signalling in H9C2 cells and cardiac performance in obese mice. These findings suggest that therapies targeting FB-α5β1 interaction may be beneficial to obesity-associated cardiometabolic complications.
- | Visudyne (verteporfin) / Novartis
Journal: Mechanotransductive Mechanisms of Biomimetic Hydrogel Cues Modulating Meckel's Cartilage Degeneration. (Pubmed Central) - Jun 22, 2022
Moreover, verteporfin (YAP inhibitor) and integrin-β1 antibody block the substrate stiffness-induced degeneration by suppressing the expressions of MMP-1 and MMP-13. These data provide new insights into the interplay between biochemical and mechanical cues determining the fate of Meckel's cartilage.
- Wnt1-inducible Signalling Pathway Protein 1 Contributes To Vascular Fibrosis By Promoting Fibroblasts Phenotypic Switch And Extracellular Matrix Deposition (Salon B, Lower Level) - Jun 18, 2022 - Abstract #BCVS2022BCVS_470;
Deletion of WISP-1 alleviated hypertension induced vascular fibrosis in vivo. Modulation of WISP-1 levels may be beneficial for attenuating the effects of hypertension on vascular fibrosis, and could provide potential therapeutic targets in clinical treatment.
- | Journal: ITGB1 Suppresses Autophagy Through Inhibiting The mTORC2/AKT Signaling Pathway In H9C2 Cells. (Pubmed Central) - Jun 8, 2022
The results showed that ITGB1 inhibited myocardial hypertrophy in both H9C2 cells and heart tissues of disease model. These data highlight the regulation mechanism on autophagy by ITGB1 and the potential usefulness of the gene as a potential target for preventing heart disease.
- | PD98059 / Wayne State University
Journal: FRET Visualization of Cyclic Stretch-Activated ERK via Calcium Channels Mechanosensation While Not Integrin β1 in Airway Smooth Muscle Cells. (Pubmed Central) - Jun 8, 2022
FRET measurements showed apparent ERK activation by mechanical stretch, which was abolished by ERK inhibitor PD98059 pretreatment...Furthermore, the ER IPR-dependent ERK activation was not dependent on phospholipase C-IP signal, indicating possibly more mechanical mechanism for IPR activation. It is concluded from our study that the mechanical stretch activated intracellular ERK signal in ASM cells through membrane Ca channels mechanosensation but not integrin β1, which was mediated by actin cytoskeleton.
- | avutometinib (VS-6766) / Verastem
Preclinical, Journal: Integrin/TGF-β1 Inhibitor GLPG-0187 Blocks SARS-CoV-2 Delta and Omicron Pseudovirus Infection of Airway Epithelial Cells In Vitro, Which Could Attenuate Disease Severity. (Pubmed Central) - May 30, 2022
Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced the inhibition of pseudovirus infection by GLPG-0187...Moreover, the inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and it may mitigate COVID-19 severity through decreased TGF-β1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.