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82 News |  |
- | Tafinlar (dabrafenib) / Novartis, CI-1040 / Pfizer
Journal: SNHG14 promotes triple-negative breast cancer cell proliferation, invasion, and chemoresistance by regulating the ERK/MAPK signaling pathway. (Pubmed Central) - Nov 21, 2024
Compared with the DMSO group, the proliferation of Docetaxel-resistant MDA-MB-231 cells was decreased in Dabrafenib, PD184352, and FR180204 treatment groups. SNHG14 knockdown inhibits TNBC progression by regulating the ERK/MAPK signaling pathway, which provides evidence for SNHG14 as a potential target for TNBC therapy.
- | LY294002 / Eli Lilly, CI-1040 / Pfizer
Journal, IO biomarker: Cell Division Cycle 42 Improves Renal Functions, Fibrosis, Th1/Th17 Infiltration and Inflammation to Some Degree in Diabetic Nephropathy. (Pubmed Central) - Nov 14, 2024
However, the treatment of LY294002 and CI-1040 had limited effect on attenuating CDC42's functions on renal function and fibrotic markers. CDC42 improves renal functions, fibrosis, Th1/Th17 infiltration and inflammation to some degree in DN mice, these functions may be independent to AKT and ERK pathways.
- CI-1040 / Pfizer
Observational data, Journal: Circulating IL-17F, but not IL-17A, is elevated in severe COVID-19 and leads to an ERK1/2 and p38 MAPK-dependent increase in ICAM-1 cell surface expression and neutrophil adhesion on endothelial cells. (Pubmed Central) - Nov 4, 2024
The contribution of two Mitogen Activated Protein Kinase (MAPK) pathways was determined using small molecule inhibitors PD184352 (a MKK1/MKK2 inhibitor) and BIRB0796 (a p38 MAPK inhibitor)...Overall, these results have identified an association between two cytokines of the IL-17 family (IL-17D and IL-17F) with COVID-19 and disease severity. Considering that IL-17F stimulation promotes neutrophil adhesion to the endothelium in a MAPK-dependent manner, it is attractive to speculate that this pathway may contribute to pathogenic immunothrombosis in concert with other molecular effectors.
- Real-world prevalence of PD-L1 positivity in early-stage/metastatic triple-negative breast cancer (eTNBC/mTNBC): primary results and pathology insights from the global retrospective observational VANESSA study (Halls 2-3) - Nov 1, 2024 - Abstract #SABCS2024SABCS_714;
- | CI-1040 / Pfizer
Journal: Equine Endothelial Cells Show Pro-Angiogenic Behaviours in Response to Fibroblast Growth Factor 2 but Not Vascular Endothelial Growth Factor A. (Pubmed Central) - Jun 19, 2024
Pharmacological inhibitors of FGF receptor 1 (FGFR1) (SU5402) or mitogen-activated protein kinase (MEK) (PD184352) blocked FGF2-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling...These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for studying angiogenic processes in horses and lay the foundations for comparative studies of EC biology in horses versus humans.
- | Koselugo (selumetinib) / Merck (MSD), AstraZeneca, CI-1040 / Pfizer
Journal: Establishment and validation of a gene mutation-based risk model for predicting prognosis and therapy response in acute myeloid leukemia. (Pubmed Central) - Jun 4, 2024
HR cases were more sensitive to erlotinib, CI-1040, and AZD6244. These findings supplemented the understanding of gene mutations in AML, and constructed models had good application prospect to provide effective information for predicting prognosis and treatment response of AML.
- | CI-1040 / Pfizer
Journal, Gene Signature: Identification and validation of a glycosyltransferase gene signature as a novel prognostic model for lung adenocarcinoma. (Pubmed Central) - Apr 22, 2024
We identified potential therapeutic drugs, including the MEK inhibitor (PD-184352)...We identified a distinct LUAD GT gene signature, and these differentially expressed mRNAs could serve as valuable prognostic biomarkers and therapeutic targets. Furthermore, we experimentally validated their expression levels and identified potential therapeutic agents.
- | mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, Mekinist (trametinib) / Novartis, BeiGene, CI-1040 / Pfizer
Preclinical, Journal: MEK1/2 inhibition decreases pro-inflammatory responses in macrophages from people with cystic fibrosis and mitigates severity of illness in experimental murine methicillin-resistant Staphylococcus aureus infection. (Pubmed Central) - Feb 18, 2024
Wild-type mice treated with PD0325901 had significant reduction in neutrophil-mediated inflammation compared to vehicle treatment groups, with preserved clearance of bacteria in lung, liver, or spleen 1 day after infection in either wild-type or CF mouse models. In summary, this study provides the first data evaluating the therapeutic potential of MEK1/2 inhibitor to modulate CF immune cells and demonstrates that MEK1/2 inhibitors diminish pro-inflammatory responses without impairing host defense mechanisms required for acute pathogen clearance.
- | Journal, PARP Biomarker: Qing Yan Li Ge Tang Induces Apoptosis in Human OEC-M1 Oral Cancer Cells. (Pubmed Central) - Dec 4, 2023
Moreover, only Bay11-7082, the NF-?B inhibitor, could suppress QYLGT-induced the release of cytokeratin 18 fragments from OEC-M1 cells. QYLGT induced apoptosis in OEC-M1 cells via the NF-?B pathway.
- | cisplatin / Generic mfg.
Preclinical, Journal: Crocin Combined With Cisplatin Regulates Proliferation, Apoptosis And Emt Of Gastric Cancer Cells Via The Fgfr3/Mapk/Erk Pathway In Vitro And In Vivo. (Pubmed Central) - Sep 18, 2023
Still, this effect could be counteracted by PD184352, which simultaneously regulated the proliferation, apoptosis, and EMT of AGS cells. In conclusion, crocin, combined with DDP, inhibits proliferation, apoptosis, and EMT of GC through the FRFR3/MAPK/ERK pathway.
- | CI-1040 / Pfizer
Journal: PD184352 exerts anti-inflammatory and antioxidant effects by promoting activation of the Nrf2/HO-1 axis. (Pubmed Central) - Apr 25, 2023
Finally, the anti-inflammatory and antioxidant effects of PD184352 were shown to be partially dependent on Nrf2 activation. Our study reveals the potential role of PD184352 as an antioxidant and provides a new strategy for OA treatment.
- | Hepcludex (bulevirtide) / Gilead
Journal: Evaluation of the drug-drug interaction potential of the novel hepatitis B and D virus entry inhibitor bulevirtide at OATP1B in healthy volunteers. (Pubmed Central) - Apr 24, 2023
Our study reveals the potential role of PD184352 as an antioxidant and provides a new strategy for OA treatment. A midazolam microdose was applied to quantify CYP3A4 activity...The 5
- CI-1040 / Pfizer
Dysregulation of Mitochondrial Dynamics via Dynamin-Related Protein 1 Implicated in Dedifferentiated Liposarcoma (Ballroom A) - Jan 3, 2023 - Abstract #SSO2023SSO_134;
Pharmacologic inhibition of DRP1 by Mdivi-1 or PD184352 in vitro promotes an elongated mitochondrial morphology, reduces cell growth and enhances chemosensitivity. Further investigation into the dysregulation of mitochondrial dynamics may reveal a novel treatment strategy to overcome chemoresistance.
- | CI-1040 / Pfizer
Journal: Sulforaphane attenuates cancer cell-induced atrophy of C2C12 myotubes. (Pubmed Central) - Dec 20, 2022
Co-administration of Nrf2 inhibitors (ML-385) or MEK inhibitors (PD184352) revealed SFN's attenuation of atrophy was blocked by ERK inhibition. These data support the chemoprotective and antioxidative function of SFN in myotubes, highlighting its therapeutic potential for cancer-related muscle wasting.
- | PD98059 / Wayne State University, CI-1040 / Pfizer
Journal: GPR120-ERK1-Srebp1c signaling pathway regulates long-chain polyunsaturated fatty acids biosynthesis in marine teleost Siganus canaliculatus. (Pubmed Central) - Nov 23, 2022
CI-1040-treated cells showed significantly higher DHA content, but the other treatment groups (except PD98059) showed significantly lower DHA content. These results indicate that the GPR120-ERK1-Srebp1c signaling pathway regulates rabbitfish LC-PUFA biosynthesis, representing a novel regulatory mechanism in vertebrates.
- | Kinaction (masitinib) / AB Science
Journal: Masitinib analogues with the N-methylpiperazine group replaced - A new hope for the development of anti-COVID-19 drugs. (Pubmed Central) - Nov 22, 2022
These structural alterations can help explain the inhibitory mechanisms of these analogues against the target enzyme. Thus, our studies provide avenues for the design of new masitinib analogues as the SARS-CoV-2 M inhibitors.
- | neflamapimod (VX-745) / EIP Pharma, CI-1040 / Pfizer
Preclinical, Journal: IL-33 induces granzyme C expression in murine mast cells via an MSK1/2-CREB dependent pathway. (Pubmed Central) - Nov 8, 2022
The promoter for granzyme C contains a potential CREB binding site. Bone marrow derived mast cells from either MSK1/2 double knockout or CREB Ser133Ala knockin mice were unable to upregulate granzyme C. Together these results indicate that IL-33 induced granzyme C expression in mast cells is regulated by an MSK1/2-CREB dependent pathway.
- | CI-1040 / Pfizer
Journal, Gene Signature: A Three-Gene Signature for Predicting the Prognosis of Patients Treated with Transarterial Chemoembolization (TACE) and Identification of PD-184352 as a Potential Drug to Reverse Nonresponse to TACE. (Pubmed Central) - Oct 11, 2022
We constructed a TACE-specific three-gene signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment. PD-184352 might have potential as a drug to improve TACE efficacy.
- mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, Mekinist (trametinib) / Novartis, CI-1040 / Pfizer
Anti-inflammatory effects of MEK1/2 inhibitors on cystic fibrosis macrophages (Exhibition Hall) - Oct 8, 2022 - Abstract #NACFC2022NACFC_1093;
These data support the hypothesis that MEK1/2 inhibitorcompounds can be used to reduce detrimental inflammation withoutimpairing host defense mechanisms. Future studies will evaluate theeffects of MEK1/2 inhibitor compounds on the effector functions of CFneutrophils and on the in vivo response to infection.
- | CI-1040 / Pfizer
Journal: Direct Targeting of the Raf-MEK-ERK Signaling Cascade Inhibits Neuroblastoma Growth. (Pubmed Central) - Sep 24, 2022
Furthermore, CI-1040 significantly inhibits tumor growth in different NB 3D spheroidal tumor models in a dose-dependent manner and by directly inhibiting spheroidal tumor cells. Overall, our findings highlight that direct inhibition of the Raf-MEK-ERK pathway is a novel therapeutic approach for NB, and further developing repurposing strategies using CI-1040 is a clinically tractable strategy for effectively treating NB.
- | Journal, Pan tumor: Pan-cancer gene expression analysis: Identification of deregulated autophagy genes and drugs to target them. (Pubmed Central) - Sep 14, 2022
Overall, our findings shed light on the most frequent cancer-associated autophagy genes, potential autophagy targets and molecules for cancer treatment. These findings can accelerate autophagy modulation in cancer therapy.
- | Journal: Searching for Blockers of Dengue and West Nile Virus Viroporins. (Pubmed Central) - Sep 3, 2022
In contrast, idasanutlin, benzbromarone, 5-azacytidine, and plerixafor were effective against West Nile Virus MgM. These drugs can serve as future antiviral therapeutic agents following subsequent in vitro and in vivo efficacy studies.
- | CI-1040 / Pfizer
Journal: The role of MEK1/2 and MEK5 in melatonin-mediated actions on osteoblastogenesis, osteoclastogenesis, bone microarchitecture, biomechanics and bone formation. (Pubmed Central) - Aug 22, 2022
Furthermore, CRISPR/Cas9 knockout of MEK1 or MEK5 in mMSCs seeded on PLGA scaffolds and placed into critical-size calvarial defects in Balb(c) mice (male and female) revealed that treatment with melatonin (15mg/L; p.o., nightly, 90 days) mediates sex-specific actions of MEK1 and MEK5 in new bone formation. This study is the first to demonstrate a role for MEK1/2 and MEK5 in modulating melatonin-mediated actions on bone formation in vivo and in a sex-specific manner.
- | Journal, Tumor Mutational Burden, PARP Biomarker: Identifying the role of transient receptor potential channels (TRPs) in kidney renal clear cell carcinoma and their potential therapeutic significances using genomic and transcriptome analyses. (Pubmed Central) - Jul 16, 2022
Finally, calibration curves were used to validate the nomogram with a satisfactory predictive survival probability. In conclusion, this research provides useful insight that can aid and guide clinical practice and scientific research.
- | CI-1040 / Pfizer
Journal: A superior loading control for the cellular thermal shift assay. (Pubmed Central) - Apr 26, 2022
A reduction in data variance and standard deviations was observed after normalisation. Conclusively, APP-αCTF is a superior CETSA loading control that can be used as a standard for this technique.
- Mekinist (trametinib) / Novartis, CI-1040 / Pfizer
Processing body dynamics drive non-genetic MEKi toleranceby fine-tuning KRAS and NRAS translation (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_6838;
Lung, breast, and melanoma cancer cells were incubated with MEKi inhibitors (PD184352 and trametinib). Altogether we describe here a new intricate mechanism involving LLPS and DDX6 in the translation regulation of essential cellular pathways that pave the way for future therapies targeting PBs to improve cancer targeted-drug therapies that are currently developed to target KRAS or NRAS unconnectedly.
- | chloroquine phosphate / Generic mfg., hydroxychloroquine / Generic mfg., sirolimus / Generic mfg.
Journal: Metalloproteinase 1 downregulation in neurofibromatosis 1: Therapeutic potential of antimalarial hydroxychloroquine and chloroquine. (Pubmed Central) - Oct 16, 2021
Moreover, the MMP1-upregulating activity of those lysosomal blockers was dependent on aryl hydrocarbon receptor (AHR) activation and ERK phosphorylation. Our findings suggest that lysosomal blockers are potential candidates for the treatment of Neurofibromatosis 1 neurofibroma.
- | CI-1040 / Pfizer
Journal, IO biomarker: Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma. (Pubmed Central) - Sep 28, 2021
We constructed a new ferroptosis-related mRNA/lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.
- | CI-1040 / Pfizer
Journal: Protein kinase Cα promotes proliferation and migration of schwann cells by activating ERK signaling pathway. (Pubmed Central) - May 15, 2021
PD184352, an inhibitor of MEK1, reversed the effect induced by PMA on SCs...Furthermore, PKCα also exhibited a neuroprotective role by upregulating the expression of neurotrophic factors in SCs. To sum up, this study offers novel insights for clarifying our understanding of the involvement of PKCα in the mechanism of peripheral nerve degeneration as well as regeneration.
- || ATR-002 / Atriva Therap
PK/PD data, Preclinical, Journal: Antiviral efficacy against Influenza virus and pharmacokinetic analysis of a novel MEK-inhibitor, ATR-002, in cell culture and in the mouse model. (Pubmed Central) - Mar 27, 2021
Our results thereby demonstrate the in vivo superiority of the active metabolite ATR-002 over CI-1040 as an antiviral agent despite its weaker cell membrane permeability. Therefore, ATR-002 is an attractive candidate for development as an efficient antiviral agent, especially given the fact that a treatment based on cellular pathway inhibition would be far less likely to lead to viral drug resistance.
- mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, Mekinist (trametinib) / Novartis, CI-1040 / Pfizer
[VIRTUAL] Targeting Eukaryotic Kinase Pathways as an Anti-Inflammatory Approach for Cystic Fibrosis () - Mar 14, 2021 - Abstract #ATS2021ATS_1980;
Results from these studies demonstrate that the MEK1/2-ERK1/2 pathway is activated in the human CF tissue, and indicate that inhibition of this pathway in leukocytes is a target with anti-inflammatory potential in CF pulmonary disease. Inhibition of the MEK1/2 pathway did not impair critical host defense responses during in vitro leukocyte phagocytosis assays.
- | CI-1040 / Pfizer
Journal: Current incidence and future projections of fragility hip fractures in Sri Lanka. (Pubmed Central) - Jan 3, 2021
Inhibition of the MEK1/2 pathway did not impair critical host defense responses during in vitro leukocyte phagocytosis assays. Although the observed hip fracture rate was low when compared with other countries, the number of hip fracture would increase from the current 10 per day to around 33 in 2051.
- | Zykadia (ceritinib) / Novartis, CI-1040 / Pfizer
Preclinical, Journal: A mass spectrometry-based proteome map of drug action in lung cancer cell lines. (Pubmed Central) - Dec 16, 2020
Aggregating drug response across cell lines also revealed that one-quarter of compounds modulated the abundance of one of their known protein targets. Finally, the proteomic data led us to discover that inhibition of mitochondrial function is an off-target mechanism of the MAP2K1/2 inhibitor PD184352 and that the ALK inhibitor ceritinib modulates autophagy.
- | quercetin (LY294002) / Eli Lilly, CI-1040 / Pfizer
Journal: NMDA receptor-dependent signalling pathways regulate arginine vasopressin expression in the paraventricular nucleus of the rat. (Pubmed Central) - Oct 25, 2020
Using pharmacological treatments, our data further reveal that the activation of ERK1/2 (PD184352), CaMKII (KN-62) and PI3K (LY294002; 740 Y-P) is involved in the NMDA-induced AVP gene expression in the PVN. Together, this study identifies NMDA-mediated cell signalling pathways that regulate AVP gene expression in the rat PVN.
- | CI-1040 / Pfizer
Journal: MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors. (Pubmed Central) - Feb 26, 2020
MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK-MAPK-ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.
- | CI-1040 / Pfizer
Journal: Prodigiosin induces apoptosis and inhibits autophagy via the extracellular signal-regulated kinase pathway in K562 cells. (Pubmed Central) - Feb 14, 2020
When ERK1/2 phosphorylation was blocked by PD184352, prodigiosin-induced apoptosis and the inhibition of autophagy decreased significantly. Taken together, these results demonstrated that the ERK signaling pathway was involved in prodigiosin-induced apoptosis and prodigiosin-inhibited autophagy.
- | U0126 / Promega, CI-1040 / Pfizer, Nexavar (sorafenib) / Bayer, Amgen
Preclinical, Journal: Identification of functional MKK3/6 and MEK1/2homologs from Echinococcus granulosus and investigation of protoscolecidal activity of MAPK signaling pathway inhibitors in vitro and in vivo. (Pubmed Central) - Jan 29, 2020
In vivo treatment with sorafenib tosylate or U0126-EtOH for 4 weeks of E. granulosus s.s.-infected mice demonstrated a reduction in parasite weight, but the results did not show significant difference. In conclusion, the MAPK cascades were identified as new targets for drug development and E. granulosus was efficiently inhibited by their inhibitors in vitro The translation of these findings into in vivo efficacy requires further adjustment of treatment regimens using sorafenib tosylate or, possibly, other kinase inhibitors.
- dexamethasone / Generic mfg., doxycycline / Generic mfg.
MAPK-ERK Pathway Activation: The Achilles’ Heel of IL-7R‒Induced Steroid Resistance (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2112;
We generated doxycycline-inducible SUP-T1 and P12 Ichikawa cell line models that can overexpress specific IL-7R signaling mutants...Exposure to each of three MEK-inhibitors CI1040, Selumetinib or Trametinib abolished not only phospho-ERK but also phosphorylation of BIM...Refractory/relapse T-ALL patients are now eligible for the current phase 1/2 MEK-inhibitor‒dexamethasone (SeluDex) trial. We are using mass-spectrometry to determine the exact phospho-sites in BIM that drives steroid resistance that can serve as a valuable biomarker.
- | CI-1040 / Pfizer
Journal: Metabolic conversion of CI-1040 turns a cellular MEK-inhibitor into an antibacterial compound. (Pubmed Central) - Oct 10, 2019
Surprisingly, ATR-002 also led to reduced bacterial growth in suspension cultures, reduced stress- and antibiotic tolerance without resistance induction. Our data identified for the first time that a particular MEK-inhibitor metabolite exhibits direct antibacterial activity, which is likely due to interference with the bacterial PknB kinase/Stp phosphatase signalling system.
- | PIK-75 / Pathway Therapeutics, CI-1040 / Pfizer
Journal: Phosphoinositide 3-kinase p110α negatively regulates thrombopoietin-mediated platelet activation and thrombus formation. (Pubmed Central) - Sep 20, 2019
Acetylsalicylic acid (ASA) blocked the enhancement of thrombus formation by TPO in both WT and p110α KO mice. Together, these results demonstrate that p110α negatively regulates TPO-mediated enhancement of platelet function by restricting ERK phosphorylation and TxA synthesis in a manner independent of its kinase activity.
- | quercetin (LY294002) / Eli Lilly, CI-1040 / Pfizer
Journal, PARP Biomarker, IO Biomarker: VEGFC/VEGFR3 Signaling Regulates Mouse Spermatogonial Cell Proliferation via the Activation of AKT/MAPK and Cyclin D1 Pathway and Mediates the Apoptosis by affecting Caspase 3/9 and Bcl-2. (Pubmed Central) - Aug 30, 2019
Collectively, these data suggested that VEGFC/VEGFR3 signaling promotes the proliferation of GC-1 cells via the AKT /MAPK and cyclin D1 pathway and it inhibits the cell apoptosis through Caspase-3/9, PARP and Bcl-2. Thus, this study sheds a novel insight to the molecular mechanisms underlying the fate decisions of mammalian spermatogonia.
- | CI-1040 / Pfizer
Journal: PRMT5 promotes cell proliferation by inhibiting BTG2 expression via the ERK signaling pathway in hepatocellular carcinoma. (Pubmed Central) - Jul 7, 2019
Furthermore, we found that PRMT5-induced ERK phosphorylation regulated BTG2 expression in HCC cells, whereas pretreatment with a selective ERK1/2 inhibitor (PD184352) significantly reversed the effect of PRMT5 on BTG2 expression. Our results indicated that PRMT5 promotes HCC proliferation by downregulating BTG2 expression via the ERK pathway.
- | Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Clinical, Journal: Cytarabine-Resistant FLT3-ITD Leukemia Cells are Associated with TP53 Mutation and Multiple Pathway Alterations-Possible Therapeutic Efficacy of Cabozantinib. (Pubmed Central) - Jun 26, 2019
...MV4-11-P and MV4-11-R showed similar sensitivity to cabozantinib, sorafenib, and MK2206, whereas MV4-11-R showed resistance to CI-1040 and idarubicin...Cabozantinib effectively inhibited tumor growth and prolonged survival time in mice bearing MV4-11-R-derived tumors. Together, our findings suggest that Mcl-1 and Akt phosphorylation are potential therapeutic targets for p53 mutants and that cabozantinib is an effective treatment in cytarabine-resistant FLT3-ITD-positive AML.