^
1d
New P1 trial
|
APG-2449
2d
Enrollment change
|
avutometinib (VS-6766) • defactinib (VS-6063)
3d
New P2 trial • Combination therapy
|
avutometinib (VS-6766) • defactinib (VS-6063)
8d
MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway. (PubMed, Environ Toxicol)
The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway in vivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.
Journal
|
MCM4 (Minichromosome Maintenance Complex Component 4)
|
MCM4 overexpression
|
LY294002
9d
Exploration on the construction of a bladder cancer prognostic model based on disulfidptosis-related lncRNAs and its clinical significance. (PubMed, Sci Rep)
Lastly, the drug sensitivity analysis revealed that the BLCA cells in the high-risk group showed an increased sensitivity to cisplatin, sunitinib, cetuximab, axitinib, docetaxel, saracatinib, vinblastine and pazopanib compared with those in the low-risk group. According to the Quantitative real time PCR results, we found that five lncRNAs of the risk model were more highly expressed in BCa cell lines than human immortalized uroepithelial cell line. The disulfidptosis-related lncRNA risk model has a valuable effect in assessing the prognosis of BLCA patients.
Journal • Tumor mutational burden • IO biomarker
|
TMB (Tumor Mutational Burden)
|
TMB-L
|
Erbitux (cetuximab) • cisplatin • docetaxel • sunitinib • pazopanib • Inlyta (axitinib) • saracatinib (AZD0530) • vinblastine
10d
Luteolin prevents cadmium-induced PC12 cell death by suppressing the Akt/mTOR signaling pathway. (PubMed, Medicine (Baltimore))
Moreover, inhibition of the Akt/mTOR signaling pathway with LY294002 (a PI3K inhibitor) enhanced the protective effect of Lut against Cd-induced cell death by suppressing Cd-induced activation of Akt, mTOR, and eukaryotic initiation factor 4E binding protein 1. The results showed that Lut prevented Cd-induced cell death partly by blocking the Akt/mTOR signaling pathway. Lut may be a potential agent for preventing Cd-induced nerve cell damage and neurodegenerative diseases.
Journal • IO biomarker
|
BAX (BCL2-associated X protein)
|
LY294002
14d
TNFRSF11B promotes the progression of bladder cancer through PI3K/AKT signaling pathway. (PubMed, Mol Cell Probes)
To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized...In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.
Journal
|
TNFRSF11B (Tumor necrosis factor receptor superfamily member 11B)
|
TNFRSF1B overexpression
|
LY294002
15d
Banxia xiexin decoction prevents the development of gastric cancer. (PubMed, World J Clin Oncol)
BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.
Journal • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2 (B-cell CLL/lymphoma 2) • IL6 (Interleukin 6)
|
EGFR expression • BCL2 expression • IL6 expression
|
capecitabine • LY294002
19d
A Multi-Omics Prognostic Model Capturing Tumor Stemness and the Immune Microenvironment in Clear Cell Renal Cell Carcinoma. (PubMed, Biomedicines)
The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes.
Journal
|
SAA2 (Serum Amyloid A2)
|
erlotinib • gefitinib • saracatinib (AZD0530)
22d
Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy. (PubMed, Sci Transl Med)
Concomitant inhibition of both FAK (with VS-4718) and rapidly accelerated fibrosarcoma and MAPK kinase (RAF-MEK) (with avutometinib) induced tumor growth inhibition and increased survival across multiple PDAC mouse models. Combination of FAK and RAF-MEK inhibition alone improved antitumor immunity and priming of T cell responses in response to chemotherapy. These findings provided the rationale for an ongoing clinical trial evaluating the efficacy of avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel in patients with PDAC and may suggest further paths for combined stromal and tumor-targeting therapies.
Journal • Stroma
|
KRAS (KRAS proto-oncogene GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
KRAS mutation
|
gemcitabine • albumin-bound paclitaxel • avutometinib (VS-6766) • defactinib (VS-6063) • VS-4718
22d
New P2 trial • Metastases
|
albumin-bound paclitaxel • Kaitanni (cadonilimab) • ifebemtinib (IN10018)
29d
SPAG4 enhances mitochondrial respiration and aerobic glycolysis in colorectal cancer cells by activating the PI3K/Akt signaling pathway. (PubMed, J Biochem Mol Toxicol)
Finally, SPAG4-overexpressed CRC cells were treated with LY294002 to validate the inhibition of PI3K/Akt pathway on CRC cell malignant phenotypes...Collectively, SPAG4 plays an oncogenic role in CRC by promoting mitochondrial respiration and aerobic glycolysis through activating the PI3K/Akt signaling. These findings suggest that inhibition of SPAG4-mediated glucose metabolism may represent a potential strategy for the clinical treatment of CRC.
Journal
|
LDHA (Lactate dehydrogenase A) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • PKM (Pyruvate Kinase M1/2) • SLC2A1 (Solute Carrier Family 2 Member 1)
|
LY294002
30d
The role and mechanism of NRG1/ErbB4 in inducing the differentiation of induced pluripotent stem cells into cardiomyocytes. (PubMed, BMC Cardiovasc Disord)
In conclusion, promoting the expression of NRG1/ErbB4 induced the differentiation of iPSC into cardiomyocytes, possibly through modulation of the PI3K/Akt signaling pathway.
Journal
|
NRG1 (Neuregulin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
|
AKT1 overexpression • ERBB4 expression
|
LY294002
1m
Assessment of the in vitro metabolic stability of CEP-37440, a selective FAK/ALK inhibitor, in HLMs using fast UPLC-MS/MS method: in silico metabolic lability and DEREK alerts screening. (PubMed, Front Chem)
Consequently, it is postulated that the administration of CEP-37440 to patients may not lead to the accrual of dosages within the human organs. According to in silico P450 metabolic and DEREK software, minor structural alterations to the ethanolamine moiety or substitution of the group in drug design have the potential to enhance the metabolic stability and safety profile of novel derivatives in comparison to CEP-37440.
Preclinical • Journal
|
ALK (Anaplastic lymphoma kinase)
|
CEP-37440
1m
5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours (clinicaltrials.gov)
P1/2, N=182, Recruiting, Institute of Cancer Research, United Kingdom
New P1/2 trial • Combination therapy
|
BRAF (B-raf proto-oncogene)
|
temozolomide • avutometinib (VS-6766) • defactinib (VS-6063)
1m
P3 data • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS wild-type
|
avutometinib (VS-6766) • defactinib (VS-6063)
1m
Proapoptotic and antimigration properties of osthole in combination with LY294002 against human glioma cells. (PubMed, Naunyn Schmiedebergs Arch Pharmacol)
In addition, the combination of compounds induced apoptosis. New combination of compounds shows a high pro-apoptotic potential and also inhibits the migration of gliomas cells.
Journal • Combination therapy • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CDH2 (Cadherin 2) • BECN1 (Beclin 1)
|
BCL2 expression
|
LY294002
1m
Tumor Dormancy Within the Lymphovascular Embolus Is Regulated by Multiple Metabolism-signaling Pathways. (PubMed, Anticancer Res)
An increase in our understanding of dormancy from the standpoint of internal signaling pathways might ultimately provide clues to the external stimuli (starvation, hypoxia or other not yet understood phenomena) that act through these pathways to maintain or disrupt dormancy.
Journal
|
CDH1 (Cadherin 1)
|
LY294002 • dorsomorphin (Compound C)
2ms
Sulfate-Reducing Bacteria Induce Pro-Inflammatory TNF-α and iNOS via PI3K/Akt Pathway in a TLR 2-Dependent Manner. (PubMed, Microorganisms)
LY294002, a PI3K/Akt signaling inhibitor, and TL2-C29, a TLR 2 antagonist, inhibited DSV-induced PI3K/AKT pathway. Thus, DSV induces pro-inflammatory TNF-α and iNOS via PI3K/Akt pathway in a TLR 2-dependent manner. Taken together, our study identifies a novel mechanism by which SRB such as Desulfovibrio may trigger inflammation in diseases associated with SRB overgrowth.
Journal • IO biomarker
|
TNFA (Tumor Necrosis Factor-Alpha)
|
LY294002
2ms
Effects of pleiotrophin (PTN) on the FAK inhibitor Y15 in breast cancer cells. (PubMed, Int J Biol Macromol)
It was hypothesized that PTN and Y15 regulate the proliferation and apoptosis of breast cancer cells through the AKT/PI3K pathway. The results demonstrated that PTN affects the sensitivity of the kinase inhibitor Y15, and PTN silencing and Y15 may inhibit the survival of breast cancer cells through the AKT/PI3K pathway, which lays the foundation for subsequent in-depth research on the clinical treatment of breast cancer.
Journal • PARP Biomarker
|
CASP3 (Caspase 3)
2ms
MLPH regulates EMT in pancreatic adenocarcinoma through the PI3K-AKT signaling pathway. (PubMed, J Cancer)
LY294002 blocked the MLPH overexpression-mediated enhanced cell invasion and migration and inhibited EMT-associated marker expression...MLPH regulated EMT to mediate PAAD cell invasive migration through the PI3K-AKT pathway. The results indicated that MLPH is a possible target for blocking PAAD metastasis.
Journal
|
MLPH (Melanophilin)
|
MLPH overexpression
|
LY294002
2ms
Prognostic value of anoikis-related genes revealed using multi-omics analysis and machine learning based on lower-grade glioma features and tumor immune microenvironment. (PubMed, Heliyon)
The high-risk group was characterized by a "cold" tumor microenvironment (TME), a lower IDH1 mutation rate (61.7 % vs. 91.4 %), a higher TP53 mutation rate (53.7 % vs. 38.9 %), and greater sensitivity to targeted therapies such as QS11 and PF-562271...The robustness of this prognostic model was further validated through internal cross-validation and across three external cohorts. The evidence from our research suggests that ARGs could potentially serve as reliable indicators for evaluating immunotherapy effectiveness and forecasting clinical results in patients with LGG.
Journal • IO biomarker • Machine learning
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
TP53 mutation • IDH1 mutation
|
benzesulfonate (PF-562271)
2ms
A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients with Progressive Meningiomas (clinicaltrials.gov)
P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Oct 2024 --> Jan 2028 | Trial primary completion date: Oct 2024 --> Jan 2026
Trial completion date • Trial primary completion date
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PTCH1 (Patched 1) • CDK4 (Cyclin-dependent kinase 4) • NF2 (Neurofibromin 2) • SMO (Smoothened Frizzled Class Receptor) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)
|
PIK3CA mutation • PTEN mutation • CDKN2A mutation • PTCH1 mutation • NF2 mutation • AKT1 mutation • SMO mutation • PIK3CA mutation + PTEN mutation • CDK4 mutation
|
Verzenio (abemaciclib) • Truqap (capivasertib) • Erivedge (vismodegib) • GSK2256098
2ms
ERK5 suppression overcomes FAK inhibitor resistance in mutant KRAS-driven non-small cell lung cancer. (PubMed, EMBO Mol Med)
Notably, ERK5 inhibition prevented the development of resistance to FAK inhibitors, significantly enhancing the efficacy of anti-tumor responses. Therefore, we propose ERK5 inhibition as a potential co-targeting strategy to counteract FAK inhibitor resistance in NSCLC.
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12D
2ms
STC2 knockdown inhibits cell proliferation and glycolysis in hepatocellular carcinoma through the PI3K/Akt/mTOR pathway-mediated autophagy induction. (PubMed, Arch Biochem Biophys)
STC2 knockdown inhibited cell proliferation and glycolysis in HCC through the PI3K/Akt/mTOR pathway-mediated autophagy induction.
Journal
|
IGF1 (Insulin-like growth factor 1) • STC2 (Stanniocalcin 2) • BECN1 (Beclin 1) • PKM (Pyruvate Kinase M1/2) • SLC2A1 (Solute Carrier Family 2 Member 1)
|
STC2 expression
|
LY294002
2ms
Preclinical evaluation of avutometinib and defactinib in high-grade endometrioid endometrial cancer. (PubMed, Cancer Med)
Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts. These preclinical data support the potential clinical evaluation of this combination in high-grade EAC patients.
Preclinical • Journal
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A)
|
RAS mutation
|
avutometinib (VS-6766) • defactinib (VS-6063) • VS-4718
2ms
Soft Corals-derived Dihydrosinularin Attenuates Neuronal Apoptosis in 6-hydroxydopamine-induced Cell Model of Parkinson's Disease by Regulating the PI3K Pathway. (PubMed, Curr Med Chem)
By investigating the mechanisms involved in 6-OHDA-induced neurotoxicity, we provided evidence concerning the therapeutic potential of DHS in neuroprotection. Further research into DHS and its mechanisms of action holds promise for developing novel therapeutic strategies for PD.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2)
|
BCL2 expression
|
LY294002
2ms
Exosomal CTHRC1 from cancer-associated fibroblasts facilitates endometrial cancer progression via ITGB3/FAK signaling pathway. (PubMed, Heliyon)
Overexpression of CTHRC1 in secreted exosomes promotes the metastatic ability of EC cells in mouse models and may be eliminated by Defactinib, an inhibitor of FAK Tyr397 phosphorylation. Moreover, overexpression of CTHRC1 was increased in EC patients, elevating with cancer progression, and correlated with negative tumor prognosis. Our results revealed that CAF mediated endometrial cancer progression is related to high levels of CTHRC1 and exosomal CTHRC1 derived from CAF may be a promising therapeutic strategy for metastatic endometrial cancer.
Journal
|
ITGB3 (Integrin Subunit Beta 3)
|
defactinib (VS-6063)
2ms
KIFC3 promotes the proliferation, migration and invasion of non-small cell lung cancer through the PI3K/AKT signaling pathway. (PubMed, Sci Rep)
This promotion effect could be inhibited by a specific inhibitor of the PI3K/Akt pathway, LY294002. Co-immunoprecipitation assays confirmed the interaction between endogenous/exogenous KIFC3 and PI3Kp85α. Tumor formation experiments in nude mice confirmed that KIFC3 overexpression promoted the proliferation, migration and invasion of NSCLC cells in vivo and performed its biological function through the PI3K/Akt signaling pathway.In conclusion, KIFC3 promotes the malignant behavior of NSCLC cells through the PI3K/Akt signaling pathway.
Journal
|
CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • MMP2 (Matrix metallopeptidase 2) • RHOA (Ras homolog family member A)
|
CCND1 expression • CDK6 expression
|
LY294002
2ms
Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer. (PubMed, Cell Death Discov)
Inhibiting autophagy by autophagy inhibitor LY294002 remarkably enhanced αCLDN18.2-MMAE-induced cytotoxicity and caspase-mediated apoptosis, indicating the cytoprotective role of autophagy in CLDN18.2-directed ADC-treated gastric cancer cells...Besides, the Akt/mTOR pathway inactivation was demonstrated to be implicated in the autophagy initiation in αCLDN18.2-MMAE-treated gastric cancer cells. In conclusion, our study highlighted a groundbreaking investigation into the mechanism of the CLDN18.2-directed ADC, focusing on the crucial role of autophagy, providing a novel insight to treat gastric cancer by the combination of CLDN18.2-directed ADC and autophagy inhibitor.
Journal • PARP Biomarker
|
CLDN18 (Claudin 18) • CASP9 (Caspase 9)
|
CLDN18.2 positive • CLDN18.2 overexpression • CLDN1 overexpression
|
LY294002
2ms
Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis. (PubMed, Oncogene)
We have previously identified that BET inhibition can selectively reduce growth of the NF2-null schwannoma and Schwann cells in vitro and tumorigenesis in vivo and, separately, reported that inhibition of Focal Adhesion Kinase 1 (FAK1) via crizotinib has antiproliferative effects in NF2-null Schwann cells...Further, we identify the mechanism of action through the downregulation of FAK1 transcription by BET inhibition, which potentiates inhibition of FAK by 100-fold. Our findings suggest that combined targeting of BET and FAK1 may offer a potential therapeutic option for the treatment of NF2-related schwannomas.
Journal
|
NF2 (Neurofibromin 2)
|
Xalkori (crizotinib)
3ms
Identification of Treatment Concentrations of Defactinib or VS-6766 for the Treatment of Patients With Glioblastoma (clinicaltrials.gov)
P1, N=12, Recruiting, Emory University | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025
Trial completion date • Trial primary completion date
|
avutometinib (VS-6766) • defactinib (VS-6063)
3ms
Hesperetin regulates PI3K/Akt and mTOR pathways to exhibit its antiproliferative effect against colon cancer cells. (PubMed, Biotech Histochem)
Interestingly, hesperetin enhanced the effects of Akt inhibitor LY294002 and mTOR inhibitor rapamycin. This study documented the potential of hesperetin to induce apoptosis through simultaneous acceleration over the autophagic process in colon cancer cells. Thus, hesperetin played a beneficial therapeutic role in preventing colon carcinoma growth by regulating the Akt and mTOR signaling axis.
Journal
|
PTEN (Phosphatase and tensin homolog) • BECN1 (Beclin 1)
|
sirolimus • LY294002
3ms
Treatment with autophagic inhibitors enhances oligonol‑induced apoptotic effects in nasopharyngeal carcinoma cells. (PubMed, Biomed Rep)
Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.
Journal • PARP Biomarker
|
CASP8 (Caspase 8) • BECN1 (Beclin 1)
|
LY294002
3ms
Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes. (PubMed)
Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future.
Journal • IO biomarker
|
Oncotype DX® Colon Recurrence Score test
|
dasatinib • saracatinib (AZD0530)
3ms
miR-149-3p Enhances Drug Sensitivity of AML Cells by Inhibiting Warburg Effect Through PI3K/AKT Pathway. (PubMed, Cell Biochem Biophys)
miR-149-3p plays an important role in the resistance of cancer cells to cisplatin, and plays an excellent anti-tumor activity...Based on AML cells, transfection of miR-149-3p inhibitor/NC and Warburg effect inhibitor (2DG) and PI3K/AKT pathway inhibitor (LY294002) were used to investigate the mechanism of IFN-γ regulating chemotherapy resistance of AML cells through Warburg effect...Upregulation of miR-149-3p expression may potentially be a therapeutic target for AML resistance. It has been shown to inhibit PI3K/AKT pathway activation, thereby inhibiting the Warburg effect, and affecting cell proliferation, apoptosis, and drug resistance.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • LDHA (Lactate dehydrogenase A) • IFNG (Interferon, gamma) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • HK2 (Hexokinase 2) • MIR149 (MicroRNA 149) • SLC2A1 (Solute Carrier Family 2 Member 1)
|
cisplatin • LY294002
3ms
Hesperetin alleviates aflatoxin B1 induced liver toxicity in mice: Modulating lipid peroxidation and ferritin autophagy. (PubMed, Ecotoxicol Environ Saf)
In AFB1-induced HepG2 cells, the addition of PI3K inhibitor (LY294002) and AKT inhibitor (Miransertib) confirmed that hesperetin regulated the PI3K/AKT/mTOR/ULK1 pathway to inhibit ferritin autophagy and reduced the degradation of ferritin in lysosomes. In summary, our results suggest that hesperetin not only regulates the antioxidant system but also inhibits AFB1-induced ferritin hyperautophagy, thereby reducing the accumulation of iron ions to mitigate lipid peroxidation. This work provides a fresh perspective on the mechanism behind hesperetin and AFB1-induced liver damage in mice.
Preclinical • Journal
|
GPX4 (Glutathione Peroxidase 4) • CD80 (CD80 Molecule) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
|
LY294002 • miransertib (MK-7075)
3ms
Network Pharmacology Followed by Experimental Validation to Explore the Mechanism of Stigmasterol in Sangbaipi Decoction Regulating PI3K/Akt Signaling to Alleviate Acute Exacerbation of Chronic Obstructive Pulmonary Disease. (PubMed, Int J Chron Obstruct Pulmon Dis)
In AECOPD rats, LY294002 restored lung function, and it also improved lung histological abnormalities and inflammation, which was found to be potentiated by SM. SM targets PI3K/Akt signaling to reduce lung injury and inflammation in AECOPD rats.
Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1)
|
LY294002
3ms
Enrollment open • Combination therapy • IO biomarker • Metastases
|
Opdivo (nivolumab) • avutometinib (VS-6766) • defactinib (VS-6063) • ABP 206 (nivolumab biosimilar)
3ms
IL-1β-activated PI3K/AKT and MEK/ERK pathways coordinately promote induction of partial epithelial-mesenchymal transition. (PubMed, Cell Commun Signal)
IL-1β-mediated partial EMT induction was repressed by PI3K inhibitor LY294002, indicating that the PI3K/AKT pathway plays a significant role in the induction...Our findings suggest that the PI3K/AKT and MEK/ERK pathways coordinately promote the IL-1β-mediated partial EMT induction. The inhibition of not one but both pathways is expected yield clinical benefits by preventing partial EMT-related disorders such as organ fibrosis and cancer metastasis.
Journal
|
CDH1 (Cadherin 1) • VIM (Vimentin) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I)
|
LY294002
3ms
The C5AR1/TNFSF13B axis alleviates osteoarthritis by activating the PI3K/Akt/GSK3β/Nrf2/HO-1 pathway to inhibit ferroptosis. (PubMed, Exp Cell Res)
More importantly, the PI3K/Akt/GSK3β/Nrf2/HO-1 pathway inhibitor LY294002 reversed the inhibition of C5AR1 or TNFSF13B on ferroptosis of chondrocytes. Finally, we found thatC5AR1 alleviated joint tissue lesions and ferroptosis in rats and inhibited the progression of OA in the rat OA model constructed by anterior cruciate ligament transection (ACLT), which was reversed by interfering with TNFSF13B. This study shows that C5AR1 reduces the progression of OA by upregulating TNFSF13B to activate the PI3K/Akt/GSK3β/Nrf2/HO-1 pathway and thereby inhibiting chondrocyte sensitivity to ferroptosis, indicating that C5AR1 may be a potential therapeutic target for ferroptosis-related diseases.
Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • TNFSF13B (TNF Superfamily Member 13b)
|
LY294002
3ms
Unveiling the therapeutic potential of epigallocatechin gallate in liver cancer: insights from network pharmacology and in vitro assays. (PubMed, Nat Prod Res)
Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.
Preclinical • Journal
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
LY294002