The patient was treated with VT3989, a YAP/TEAD inhibitor, for 5 cycles...Downregulation of the Hippo signaling pathway via YAP/TEAD inhibition in an adult patient may result in a phenotype resembling a mild form of HPCD (Sveinsson chorioretinal atrophy), underscoring the importance of this pathway in maintenance of the adult retina and retinal pigment epithelium. As novel cancer therapeutics continue to emerge, it may be important to ensure ophthalmologic monitoring of patients on drugs targeting the Hippo pathway.

These findings, and tumor cell growth suppression were confirmed in NF2 fl/fl;Peri-Cre mouse model 7 , and in human derived schwannoma cells treated with a pan-TEAD auto palmitoylation inhibitor VT3989. 8 Our computational and experimental results confirm that TEAD1 inhibition could be a potent, targeted strategy for schwannomas.

P1, N=137, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

They demonstrated efficacy against colorectal cancer cells resistant to the KRAS-dependent clinical candidate IAG933 and confirmed the ability to inhibit TEAD4 target genes expression. Bioinformatic metabolic pathway analysis further differentiated the mechanism of action of the 6a analogs from verteporfin, a known indirect modulator of the Y:T complex. These findings establish the pyrazolo-piperidinone class as novel Y:T disruptors and provide insights into their metabolic impact on downstream effectors, offering a valuable framework for future hit-to-lead optimization and mechanism of action studies.

Here, we develop a high-content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors...We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer-relevant assays in a clinically relevant cellular model of pleural mesothelioma.

P1/2, N=336, Recruiting, Vivace Therapeutics, Inc | Phase classification: P1 --> P1/2

Current therapeutic innovation focuses on molecular diagnostics and precision targeting approaches, including direct YAP/TAZ-TEAD complex inhibitors, upstream receptor modulators, and rational combinations with immune checkpoint blockade. Future investigations should employ multi-omics profiling to delineate tumor subtype-specific regulatory architectures while advancing novel drug delivery platforms. These efforts promise to translate mechanistic insights into multi-targeted therapeutic strategies capable of overcoming resistance mechanisms and improving survival outcomes for this therapeutically challenging malignancy.

Pharmacological inhibition of YAP/TAZ-TEAD interaction by Verteporfin significantly decreased tumor cell growth, whereas specific inhibition of TEAD3 did not impact cell proliferation but affected sterol/cholesterol biosynthetic and metabolic processes. This study contributes to a better understanding of the role of Hippo effectors in glioblastoma pathophysiology. These transcription factors, particularly TEAD3, could potentially serve as therapeutic targets, especially considering recent data on cholesterol homeostasis in glioblastomas.

Our findings establish the cardiac glycoside PPM as a novel ferroptosis sensitizer that targets ATP1A1 to activate the Src-YAP/TAZ-TFRC axis, providing mechanistic insights for repurposing cardiac glycosides as ferroptosis modulators in precision combinatorial cancer therapy.

Consequently, we identified a novel hydrogen-bonding site and discovered C-2, which effectively binds to this site, as confirmed by X-ray crystallography. Furthermore, C-2 exhibited stable pharmacokinetic properties and demonstrated impressive efficacy in a mouse xenograft model.

P1, N=336, Recruiting, Vivace Therapeutics, Inc | Phase classification: P1/2 --> P1 | N=250 --> 336

We further show that inhibition of the YAP/TAZ-associated TEAD family of transcription factors blocks the development of the carcinomas and associated microenvironment. These observations demonstrate that carcinomas resulting from Hippo pathway dysregulation in the mammary epithelium are sufficient to drive cellular events that promote a basal-like tumor-associated niche and suggest that targeting dysregulated YAP/TAZ-TEAD activity may offer a therapeutic opportunity for basal-like mammary tumors.