Small-Molecule Inhibitors Targeting the Canonical WNT Signaling Pathway for the Treatment of Cancer

Liu, Zhiqing; Wang, Pingyuan; Wold, Eric A.; Song, Qiaoling; Zhao, Chenyang; Wang, Chang‐Yun; Zhou, Jia

doi:10.1021/acs.jmedchem.0c01799

Cited by 24 publications

(31 citation statements)

References 202 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The canonical Wnt pathway is CML’s most seriously impacted Wnt system [ 58 ]. Because the fusion protein BCR-ABL may actively adjust β-catenin levels in cells.…”

Section: Hippo Signaling Pathway and Interaction With Other Signaling Pathwaysmentioning

confidence: 99%

The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

Noorbakhsh¹,

Hayatmoghadam

Jamali

et al. 2021

Cancer Cell Int

View full text Add to dashboard Cite

Cancer can be considered as a communication disease between and within cells; nevertheless, there is no effective therapy for the condition, and this disease is typically identified at its late stage. Chemotherapy, radiation, and molecular-targeted treatment are typically ineffective against cancer cells. A better grasp of the processes of carcinogenesis, aggressiveness, metastasis, treatment resistance, detection of the illness at an earlier stage, and obtaining a better therapeutic response will be made possible. Researchers have discovered that cancerous mutations mainly affect signaling pathways. The Hippo pathway, as one of the main signaling pathways of a cell, has a unique ability to cause cancer. In order to treat cancer, a complete understanding of the Hippo signaling system will be required. On the other hand, interaction with other pathways like Wnt, TGF-β, AMPK, Notch, JNK, mTOR, and Ras/MAP kinase pathways can contribute to carcinogenesis. Phosphorylation of oncogene YAP and TAZ could lead to leukemogenesis, which this process could be regulated via other signaling pathways. This review article aimed to shed light on how the Hippo pathway interacts with other cellular signaling networks and its functions in leukemia.

show abstract

“…The canonical Wnt pathway is CML’s most seriously impacted Wnt system [ 58 ]. Because the fusion protein BCR-ABL may actively adjust β-catenin levels in cells.…”

Section: Hippo Signaling Pathway and Interaction With Other Signaling Pathwaysmentioning

confidence: 99%

The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

Noorbakhsh¹,

Hayatmoghadam

Jamali

et al. 2021

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“… 3 , 14 , 16 , 17 Hence, controlling the catalytic activity of tankyrase by pharmacological intervention provides an attractive tool for reducing WNT/β-catenin and Hippo signaling. 18 , 19 …”

Section: Introductionmentioning

confidence: 99%

Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II

et al. 2021

View full text Add to dashboard Cite

Tankyrase 1 and 2 (TNKS1/2) catalyze post-translational modification by poly-ADP-ribosylation of a plethora of target proteins. In this function, TNKS1/2 also impact the WNT/β-catenin and Hippo signaling pathways that are involved in numerous human disease conditions including cancer. Targeting TNKS1/2 with small-molecule inhibitors shows promising potential to modulate the involved pathways, thereby potentiating disease intervention. Based on our 1,2,4-triazole-based lead compound 1 (OM-1700), further structure–activity relationship analyses of East-, South- and West-single-point alterations and hybrids identified compound 24 (OM-153). Compound 24 showed picomolar IC 50 inhibition in a cellular (HEK293) WNT/β-catenin signaling reporter assay, no off-target liabilities, overall favorable absorption, distribution, metabolism, and excretion (ADME) properties, and an improved pharmacokinetic profile in mice. Moreover, treatment with compound 24 induced dose-dependent biomarker engagement and reduced cell growth in the colon cancer cell line COLO 320DM.

show abstract

“…[ 27 ] Recently, considerable attention has been drawn to promote tumor cell apoptosis by inhibiting the activation of the Wnt signaling pathway. [ 28 ] Consequently, conspicuous cell apoptosis was caused by administration of Bi 13 S 18 I 2 NRs and subsequent NIR laser irradiation via downregulation of the Wnt signaling pathway. In addition, the PI3K–Akt, Ras, p53, and Rap1 signaling pathways associated with cell proliferation were also significantly downregulated in the Bi 13 S 18 I 2 ‐NRs‐treated group (Figure 6d).…”

Section: Resultsmentioning

confidence: 99%

Engineering Electronic Band Structure of Binary Thermoelectric Nanocatalysts for Augmented Pyrocatalytic Tumor Nanotherapy

et al. 2021

View full text Add to dashboard Cite

treatment of tumorigenic cells because of its intrinsic advantages such as precise spatiotemporal selectivity and high specificity. [1] PTT involves the utilization of near-infrared (NIR) photoabsorbing agents to convert external NIR laser energy into local thermal energy to induce hyperthermia effect and thermal ablation of tumorigenic cells. [2] Unfortunately, tumor cells treated with hyperthermia have been demonstrated to induce thermoresistance, which substantially improves their survival capability, thus causing unsatisfactory treatment outcomes in PTT. [3] The heat-shock proteins (HSPs) have been extensively perceived as crucial factors in capacitating tumor cells to resist hyperthermia-induced cell death and initiate the defense mechanism of tumors. [4] To increase the susceptibility of tumor cells to hyperthermia effects, small-interfering RNA and specific HSP inhibitors have been utilized in hyperthermia-effectinvolved tumor treatment. [5] However, an obvious hysteretic effect appears upon the utilization of small molecular inhibitors because they can influence the existing HSPs after thermal stimulation rather than before the treatment process. In addition, these inhibitors lack generalizability as one specific inhibitor only targets one type of HSPs, thereby severely hindering their inhibition efficacy against the HSPs. [6] Hence, there is an imperative demand Photothermal therapy (PTT) has emerged as a distinct therapeutic modality owing to its noninvasiveness and spatiotemporal selectivity. However, heat-shock proteins (HSPs) endow tumor cells with resistance to heatinduced apoptosis, severely lowering the therapeutic efficacy of PTT. Here, a high-performance pyroelectric nanocatalyst, Bi 13 S 18 I 2 nanorods (NRs), with prominent pyroelectric conversion and photothermal conversion performance for augmented pyrocatalytic tumor nanotherapy, is developed. Canonical binary compounds are reconstructed by inserting a third biocompatible agent, thus facilitating the formation of Bi 13 S 18 I 2 NRs with enhanced pyrocatalytic conversion efficiency. Under 808 nm laser irradiation, Bi 13 S 18 I 2 NRs induce a conspicuous temperature elevation for photonic hyperthermia. In particular, Bi 13 S 18 I 2 NRs harvest pyrocatalytic energy from the heating and cooling alterations to produce abundant reactive oxygen species, which results in the depletion of HSPs and hence the reduction of thermoresistance of tumor cells, thereby significantly augmenting the therapeutic efficacy of photothermal tumor hyperthermia. By synergizing the pyroelectric dynamic therapy with PTT, tumor suppression with a significant tumor inhibition rate of 97.2% is achieved after intravenous administration of Bi 13 S 18 I 2 NRs and subsequent exposure to an 808 nm laser. This work opens an avenue for the design of high-performance pyroelectric nanocatalysts by reconstructing canonical binary compounds for therapeutic applications in biocatalytic nanomedicine.

show abstract

Small-Molecule Inhibitors Targeting the Canonical WNT Signaling Pathway for the Treatment of Cancer

Cited by 24 publications

References 202 publications

The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II

Engineering Electronic Band Structure of Binary Thermoelectric Nanocatalysts for Augmented Pyrocatalytic Tumor Nanotherapy

Contact Info

Product

Resources

About