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DRUG CLASS:

Wnt signalling pathway inhibitor

15d
Deciphering the value of anoikis-related genes in prognosis, immune microenvironment, and drug sensitivity of laryngeal squamous cell carcinoma. (PubMed, Pathol Res Pract)
Our prognostic signature effectively predicts LSCC prognosis, with MMP3 identified as a potential novel biomarker for LSCC treatment. Furthermore, our findings underscore the critical role of immune-based therapies in improving outcomes, especially for low-risk patients.
Journal
|
TIMP1 (Tissue inhibitor of metalloproteinases 1) • MMP3 (Matrix metallopeptidase 3)
|
AVTX-006 • WNT974
17d
Hsa_circ_0125356 promotes gemcitabine resistance by modulating WNT canonical and non-canonical pathways via miR-582-5p/FGF9 axis in non-small cell lung cancer. (PubMed, Mol Cancer)
We first demonstrated that hsa_circ_0125356 was significantly upregulated and served as a biomarker for gemcitabine resistance in NSCLC by sponging miR-582-5p/FGF9 axis to regulate the WNT canonical and non-canonical signaling pathways, which provided a new direction for identification of therapeutic targets for the treatment of gemcitabine resistance of NSCLC.
Journal
|
CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RHOA (Ras homolog family member A) • MIR582 (MicroRNA 582)
|
gemcitabine • XAV-939
18d
Targeting the DNA Damage Response through TBL1X in Mantle Cell Lymphoma. (PubMed, Blood Adv)
Combining tegavivint with PARP-1/2 inhibitor talazoparib results in synergistic MCL cell death in vitro, and in vivo this combination significantly prolonging the survival of an MCL PDX. Together, our results define the role of TBL1X in maintaining genomic stability in MCL and establish targeting TBL1X as a novel therapeutic strategy for patients with this incurable disease.
Journal • PARP Biomarker
|
CCND1 (Cyclin D1) • RAD51 (RAD51 Homolog A)
|
Talzenna (talazoparib) • tegavivint (BC2059)
23d
Discovery of a novel Wnt inhibitor DK419: Reversing temozolomide resistance in glioblastoma by switching off Wnt/β-catenin signaling pathway to inhibit MGMT expression. (PubMed, Eur J Med Chem)
The addition of the Wnt activator LiCl reversed DK419-induced effects on β-catenin nuclear translocation and Cyclin D1 and MGMT expression. For the first time, our findings demonstrate that DK419 can significantly enhance glioblastoma sensitivity to TMZ by modulating the Wnt/β-catenin pathway to downregulate MGMT expression.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase) • CCND1 (Cyclin D1)
|
temozolomide
2ms
Tegavivint for the Treatment of Relapsed or Refractory Leukemia (clinicaltrials.gov)
P1, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date
|
decitabine • tegavivint (BC2059)
2ms
Identification of a TNIK-CDK9 axis as a targetable strategy for platinum-resistant ovarian cancer. (PubMed, Mol Cancer Ther)
This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC...Our findings identified the TNIK-CDK9 axis as druggable targets mediating platinum resistance and cell viability in HGSC. With AI at the forefront of drug discovery, this work highlights how to ensure that AI findings are biologically relevant by combining compound screens with physiologically relevant models thus supporting the identification and validation of potential drug targets.
Journal
|
CDK9 (Cyclin Dependent Kinase 9) • TNIK (TRAF2 And NCK Interacting Kinase)
|
NCB-0846
2ms
The Role of Indoxyl Sulfate in Exacerbating Colorectal Cancer During Chronic Kidney Disease Progression: Insights into the Akt/β-Catenin/c-Myc and AhR/c-Myc Pathways in HCT-116 Colorectal Cancer Cells. (PubMed, Toxins (Basel))
Indoxyl sulfate activated the Akt/β-Catenin/c-Myc pathway as evidenced by the Akt inhibitor MK2206, which decreased both β-Catenin and c-Myc protein levels, and the β-Catenin inhibitor XAV-939, which reduced c-Myc protein levels. These findings indicate that the elevation of indoxyl sulfate levels in the blood, due to CKD progression, could worsen CRC by promoting the proliferation of CRC cells and enhancing EGF signaling. Therefore, indoxyl sulfate could potentially serve as a therapeutic target for CRC aggravation in patients with CKD.
Journal
|
EGFR (Epidermal growth factor receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
MK-2206 • XAV-939
2ms
A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC) (clinicaltrials.gov)
P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
Trial completion date • Trial primary completion date
|
RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • AXIN1 (Axin 1) • ZNRF3 (Zinc And Ring Finger 3)
|
APC mutation • CTNNB1 mutation • RNF43 mutation
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E7386
2ms
LGALS4 inhibits glycolysis and promotes apoptosis of colorectal cancer cells via β‑catenin signaling. (PubMed, Oncol Lett)
LGALS4 overexpression inhibited CRC cell growth, induced cell cycle arrest and enhanced 5-fluorouracil (5-FU)-induced apoptosis...The downregulatory effect of LGALS4 on glycolysis-related genes was further enhanced by the addition of the β-catenin inhibitor XAV-939...Overexpression of LGALS4 reduced the proliferation and glycolytic capacity of CRC cells and also enhanced their sensitivity to 5-FU. These results may potentially provide new perspectives for CRC treatment and targets for future clinical intervention strategies.
Journal
|
LGALS4 (Galectin 4)
|
LGALS4 expression
|
5-fluorouracil • XAV-939
2ms
Osimertinib and Tegavivint As First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)
P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | N=18 --> 24 | Trial completion date: Dec 2024 --> Jul 2029 | Trial primary completion date: Dec 2024 --> Jul 2025
Enrollment change • Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor) • NOTCH3 (Notch Receptor 3)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
|
Tagrisso (osimertinib) • tegavivint (BC2059)
2ms
Osimertinib and Tegavivint As First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)
P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | N=18 --> 24 | Trial completion date: Dec 2024 --> Jul 2029 | Trial primary completion date: Dec 2024 --> Jul 2025
Enrollment change • Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor) • NOTCH3 (Notch Receptor 3)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
|
Tagrisso (osimertinib) • tegavivint (BC2059)
3ms
FNDC1 Facilitates Proliferation, Migration, and Invasion of Breast Cancer Cells Through Modulating Wnt/β-Catenin Pathway. (PubMed, Biochem Genet)
Notably, Wnt/β-catenin activation with LiCl significantly enhanced the proliferation and epithelial-mesenchymal transformation (EMT) inhibition effect of silencing FNDC1, whereas Wnt/β-catenin inhibition with XAV-939 significantly weakened the proliferation and EMT promotion effect of FNDC1...These data suggested that FNDC1 exerts its oncogene function through modulating Wnt/β-catenin signaling pathway. In conclusion, FNDC1 promotes cell proliferation, migration, invasion, and EMT through modulating Wnt/β-catenin signaling pathway in breast cancer, providing a new idea for the development of breast cancer therapeutic targets.
Journal
|
MKI67 (Marker of proliferation Ki-67) • FNDC1 (Fibronectin Type III Domain Containing 1)
|
XAV-939
3ms
A phase I dose-escalation study of LRP5/6 antagonist BI 905677 in patients with advanced solid tumors. (PubMed, ESMO Open)
The MTD of BI 905677 was set at 2.8 mg/kg every 3 weeks. BI 905677 was well tolerated but a narrow therapeutic range and minimal efficacy led to early termination of the trial.
P1 data • Journal • Metastases
|
AXIN2 (Axin 2)
4ms
Wnt/β-Catenin Pathway-Mediated PD-L1 Overexpression Facilitates the Resistance of Non-Small Cell Lung Cancer Cells to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. (PubMed, Discov Med)
Activation of the Wnt/β-catenin pathway mediates the high expression of PD-L1 to promote the resistance of NSCLC cells to icotinib. Thus, targeted inhibition of PD-L1 expression is of benefit for the treatment of NSCLC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9)
|
PD-L1 overexpression
|
Conmana (icotinib) • foscenvivint (PRI724)
4ms
Targeting the NOTCH2/ADAM10/TCF7L2 Axis-Mediated Transcriptional Regulation of Wnt Pathway Suppresses Tumor Growth and Enhances Chemosensitivity in Colorectal Cancer. (PubMed, Adv Sci (Weinh))
Furthermore, use of adavivint or blockage of ADAM10/NOTCH2/TCF7L2 signaling enhances the chemosensitivity of CRC cells. Overall, this study provides a promising candidate for the development of small-molecule inhibitors and reveals a potential therapeutic target for CRC.
Journal
|
CCND1 (Cyclin D1) • NOTCH2 (Notch 2) • TCF7L2 (Transcription Factor 7 Like 2) • ADAM10 (ADAM Metallopeptidase Domain 10) • TCF7 (Transcription Factor 7)
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lorecivivint (SM04690)
4ms
Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells. (PubMed, Cancers (Basel))
Pharmacologic interactions between EB and the Wnt signaling inhibitors IGC-011 and PRI-724 were determined by the combination index method and showed antagonism, indicating that EB acts on the same pathway as these inhibitors...Following exposure to human liver microsomes, EB was metabolized by NADPH-dependent oxidation and UDPG-dependent glucuronidation, as evidenced by the elimination of EB cytotoxicity against SCLC cells. Taken together, these data indicate that EB, a steroid hormone in plants consumed in the human diet, is pharmacologically active in drug-sensitive and drug-resistant SCLC cells in the Wnt signaling pathway, alters apoptotic gene expression, and is a substrate for microsomal modifications.
Journal
|
BIRC5 (Baculoviral IAP repeat containing 5) • CAV1 (Caveolin 1) • CASP3 (Caspase 3) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
|
BAX expression
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foscenvivint (PRI724)
4ms
The Wnt/Pyruvate kinase, Muscle axis plays an essential role in the differentiation of mouse neuroblastoma cells. (PubMed, Neurochem Int)
The Wnt inhibitor ICG-001 and PKM activator ML-265 inhibited ATRA-induced Neuro-2a and N1E-115 differentiation, whereas RNA interference-mediated Pkm silencing promoted Neuro-2a and N1E-115 differentiation, which was reversed by PKM overexpression...These results indicate that Wnt/β-catenin signaling promotes Neuro-2a and N1E-115 differentiation by inhibiting PKM-mediated glycolysis during ATRA-induced differentiation. These findings may provide a new theoretical basis for the role of glycolysis in nerve differentiation.
Preclinical • Journal
|
PKM (Pyruvate Kinase M1/2)
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foscenvivint (PRI724)
4ms
Nafamostat mesylate sensitizes ovarian cancer cells to carboplatin by promoting the ZNF24-mediated inhibition of WNT2B. (PubMed, J Toxicol Sci)
Taken together, NM enhanced the CBP sensitivity of ovarian cancer cells by promoting the ZNF24-mediated inactivation of the WNT2B/Wnt/β-catenin axis. These findings suggest a viable treatment approach for improving CBP resistance in ovarian cancer.
Journal
|
WNT2 (Wnt Family Member 2)
|
carboplatin • nafamostat
5ms
Trial completion
|
BRAF (B-raf proto-oncogene)
|
Keytruda (pembrolizumab) • Lenvima (lenvatinib) • E7386
5ms
Activation of the WNT7B/β-Catenin Pathway Initiates GLUT1 Expression and Promotes Aerobic Glycolysis in Colorectal Cancer Cells. (PubMed, Nutr Cancer)
The WNT/β-catenin signaling pathway inhibitor, LGK974, inhibited WNT7B secretion, leading to GLUT1 levels downregulation and promotion of cell apoptosis. Ectopic tumor xenograft model experiments revealed that WNT7B promoted tumor progression in mice. Overall, our results suggest that WNT7B promotes β-catenin entry into the nucleus to initiates GLUT1 transcription, increases glucose transport and consumption, and enhances aerobic glycolysis, thus promoting tumor progression in colorectal cancer cells.
Journal
|
SLC2A1 (Solute Carrier Family 2 Member 1) • WNT7B (Wnt Family Member 7B)
|
WNT974
5ms
TARDBP drives T-cell acute lymphoblastic leukemia progression by binding MDM2 mRNA, involving β-catenin pathway. (PubMed, FASEB J)
Moreover, XAV-939, a β-catenin inhibitor, was capable of suppressing the malignant phenotypes in TARDBP-overexpressed T-ALL cells...In aggregate, we explored a promising biomarker, TARDBP, for T-ALL treatment. The underlying mechanisms might involve the interaction with MDM2 mRNA and the regulation of the β-catenin pathway.
Journal
|
TARDBP (TAR DNA Binding Protein)
|
XAV-939
5ms
Elevated Porcupine Disrupts Lipid Metabolism and Promotes Inflammatory Response in MASLD. (PubMed, Liver Int)
The current study reveals that PA-induced Porcupine disrupts lipid metabolism and promotes inflammatory response during MASLD development, which can be ameliorated by the Porcupine inhibitor Wnt974. Therefore, Porcupine may be a potential pharmacological target for the treatment of MASLD.
Journal
|
CD36 (thrombospondin receptor)
|
WNT974
5ms
E7386-J081-102: A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor (clinicaltrials.gov)
P1/2, N=301, Recruiting, Eisai Inc. | Phase classification: P1 --> P1/2 | N=181 --> 301 | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> Nov 2026
Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)
|
BRAF V600E • MSI-H/dMMR • BRAF V600 • KRAS wild-type • NRAS wild-type
|
paclitaxel • Lenvima (lenvatinib) • doxorubicin hydrochloride • E7386
6ms
Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through β-catenin/CREB interruption. (PubMed, Acta Pharm Sin B)
To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001...Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.
Journal • Metastases
|
CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
CCL4 elevation
|
foscenvivint (PRI724)
6ms
A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands (clinicaltrials.gov)
P1, N=185, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
Trial completion
|
BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43)
|
BRAF mutation • RNF43 mutation
|
spartalizumab (PDR001) • WNT974
6ms
Novel PROTAC probes targeting KDM3 degradation to eliminate colorectal cancer stem cells through inhibition of Wnt/β-catenin signaling. (PubMed, RSC Med Chem)
Compound 4 also showed dramatic ability in suppressing oncogenic Wnt signaling to eliminate colorectal CSCs and inhibit tumor growth, with around 10- to 35-fold increased potency over IOX1. In summary, this study suggests that PROTACs provide a unique molecular tool for the development of novel small molecules from the IOX1 skeleton for selective degradation of KDM3 to eliminate colorectal CSCs via suppressing oncogenic Wnt signaling.
Journal • Cancer stem
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CRBN (Cereblon) • KDM3A (Lysine Demethylase 3A)
6ms
Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression. (PubMed, Mol Oncol)
Inhibition of the Cdc2-like kinase (CLK) family by the small molecules cirtuvivint or lorecivivint results in the decreased expression of ARV7. Both inhibitors show potent anti-proliferative effects in enzalutamide-treated or -naive PC models. Thus, targeting aberrant alternative splicing at the 3'UTR of ARV7 by disturbing the CLK2/SRSF9 axis might be a valuable therapeutic approach in late stage, ARSI-resistant PC.
Journal
|
AR (Androgen receptor) • ARSI (Arylsulfatase Family Member I) • CDK1 (Cyclin-dependent kinase 1) • CLK2 (CDC Like Kinase 2) • SRSF9 (Serine And Arginine Rich Splicing Factor 9)
|
AR splice variant 7 • AR-V7 expression
|
Xtandi (enzalutamide) • lorecivivint (SM04690) • cirtuvivint (SM08502)
6ms
Role of the lncRNA/Wnt signaling pathway in digestive system cancer: a literature review. (PubMed, Eur J Med Res)
Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.
Review • Journal
|
SH3BP5-AS1 (SH3BP5 Antisense RNA 1)
|
XAV-939
7ms
Combined targeting of Hedgehog/GLI1 and Wnt/β-catenin pathways in mantle cell lymphoma. (PubMed, Hematol Oncol)
Moreover, GLI1 knockdown combined with ICG-001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β-catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients.
Journal
|
GLI1 (GLI Family Zinc Finger 1)
|
Imbruvica (ibrutinib) • doxorubicin hydrochloride • foscenvivint (PRI724)
7ms
Hypermethylated RASAL1's promotive role in chemoresistance and tumorigenesis of choriocarcinoma was regulated by TET2 but not DNMTs. (PubMed, BMC Cancer)
Taken together, the present data elucidated that reduced RASAL1 through its promoter hypermethylation regulated by TET2 promoted the tumorigenicity and chemoresistance of CC via modulating β-catenin both in vitro and in vivo.
Journal
|
TET2 (Tet Methylcytosine Dioxygenase 2)
|
methotrexate • XAV-939
8ms
Fructose-1, 6-Bisphosphate Aldolase B Suppresses Glycolysis and Tumor Progression of Gastric Cancer. (PubMed, Dig Dis Sci)
Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer.
Journal • PARP Biomarker
|
ALDOB (Aldolase, Fructose-Bisphosphate B)
|
Talzenna (talazoparib) • XAV-939
8ms
Preclinical • Journal
|
AXIN1 (Axin 1) • ANXA5 (Annexin A5)
|
foscenvivint (PRI724)
8ms
WNT inhibitory factor 1 (WIF1) is a novel fusion partner of RUNX family transcription factor 1 (RUNX1) in acute myeloid leukemia with t(12;21)(q14;q22). (PubMed, J Hematop)
Additionally, this is the first report of a RUNX1 fusion gene with the break point in intron 2, resulting in an out-of-frame fusion. Further research is needed to investigate the impact of this novel fusion on the establishment and progression of the disease.
Journal
|
RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • WIF1 (WNT Inhibitory Factor 1)
8ms
Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas. (PubMed, Drug Resist Updat)
Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model...These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.
Journal
|
MIR1290 (MicroRNA 1290)
|
WNT974
8ms
Tankyrase1/2 inhibitor XAV-939 reverts EMT and suggests that PARylation partially regulates aerobic activities in human hepatocytes and HepG2 cells. (PubMed, Biochem Pharmacol)
This work exposed a new mechanistic framework by linking PARylation to respiration and metabolism, thereby broadening the current understanding that underlies these vital processes. XAV-939 poses an immediate and straightforward strategy to improve aerobic activities, and metabolism, in (immature) cell cultures.
Journal
|
CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
XAV-939
8ms
NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9. (PubMed, Diabetes Metab J)
It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
Journal
|
MMP9 (Matrix metallopeptidase 9)
|
XAV-939
8ms
Long noncoding RNA LINC01550 inhibits colorectal cancer malignancy by suppressing the Wnt/β-catenin signaling pathway. (PubMed, J Biochem Mol Toxicol)
APC and TP53 mutations were more frequent in the low LINC01550 expression group, while the high LINC01550 expression group was significantly more sensitive to 5-fluorouracil, irinotecan, trametinib, gemcitabine, rapamycin, and XAV939. LINC01550 exerted these effects by inhibiting Wnt/β-catenin signaling. Our results suggest LINC01550 as a diagnostic and prognostic predictor in CRC that acts as a tumor suppressor and a potential therapeutic target.
Journal
|
TP53 (Tumor protein P53) • APC (APC Regulator Of WNT Signaling Pathway)
|
Mekinist (trametinib) • gemcitabine • 5-fluorouracil • irinotecan • sirolimus • XAV-939
8ms
Identification and biological evaluation of fused tetrahydroisoquinoline derivatives as Wnt/β-catenin signaling inhibitors to suppress colorectal cancer. (PubMed, Eur J Med Chem)
More importantly, compound 10 exhibits favorable pharmacokinetic parameters and significant anti-tumor efficacies in the HCT116 xenograft model. Taken together, this study furnished the discovery of candidate drug compound 10 possessing a novel fused tetrahydroisoquinoline scaffold with excellent in vitro and in vivo anti-CRC activities by targeting Hsp90 to disturb Wnt/β-catenin signaling pathway, which lay a foundation for discovering more effective CRC-targeted therapies.
Journal
|
HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
8ms
Clinical significance of TROAP in endometrial cancer and the antiproliferative and proapoptotic effects of TROAP knockdown in endometrial cancer cells: integrated utilization of bioinformatic analysis and in vitro test verification. (PubMed, Naunyn Schmiedebergs Arch Pharmacol)
Moreover, SKL2001, a Wnt/β-catenin activator, partially abrogated the effects of TROAP silencing on EC cell proliferation and apoptosis, while the signaling inhibitor XAV-939 had the opposite effect. In conclusion, TROAP knockout retarded proliferation and elicited apoptosis in EC cells by blocking the Wnt/β-catenin pathway.
Preclinical • Journal
|
CASP3 (Caspase 3) • PCNA (Proliferating cell nuclear antigen)
|
XAV-939
8ms
Stabilizing Axin leads to optic nerve hypoplasia in a mouse model of autism. (PubMed, Exp Eye Res)
Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice...The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.
Preclinical • Journal
|
AXIN1 (Axin 1)
|
XAV-939
9ms
AQP5 promotes epithelial-mesenchymal transition and tumor growth through activating the Wnt/β-catenin pathway in triple-negative breast cancer. (PubMed, Mutat Res)
In the TNBC cells, AQP5 modulates the expression levels of EMT-related proteins through activation of Wnt/β-catenin signaling pathway, thus enhancing the cell proliferation, migration and invasion while inhibiting the cell apoptosis.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CASP3 (Caspase 3) • AQP3 (Aquaporin 3)
|
foscenvivint (PRI724)
9ms
Activation of Wnt/β-catenin signaling promotes immune evasion via the β-catenin/IKZF1/CCL5 axis in hepatocellular carcinoma. (PubMed, Int Immunopharmacol)
In conclusion, our findings suggest that combined application of ICG-001 and anti-PD-1 antibody exhibits significantly enhanced antitumor efficacy. Hence, combining a WNT/β-catenin signaling pathway inhibitor with anti-PD-1 therapy may be a promising treatment strategy for patients with HCC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IKZF1 (IKAROS Family Zinc Finger 1) • CCL5 (Chemokine (C-C motif) ligand 5) • CCR5 (C-C Motif Chemokine Receptor 5)
|
foscenvivint (PRI724)