Last update 21 Nov 2024

YAP-TEAD inhibitor(Children's Medical Center Corp)

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

TEAD x YAP1

Mechanism

TEAD inhibitors(TEA domain transcription factors inhibitors), YAP1 inhibitors(Yes1 associated transcriptional regulator inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

The Children's Medical Center Corp.

Active Organization

The Children's Medical Center Corp.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with YAP-TEAD inhibitor(Children's Medical Center Corp)

100 Translational Medicine associated with YAP-TEAD inhibitor(Children's Medical Center Corp)

100 Patents (Medical) associated with YAP-TEAD inhibitor(Children's Medical Center Corp)

Literatures (Medical) associated with YAP-TEAD inhibitor(Children's Medical Center Corp)

01 Feb 2023·Molecular DiversityQ3 · CHEMISTRY

Recent advances in the green synthesis of Betti bases and their applications: a review

Q3 · CHEMISTRY

Review

Author: Parveen, Sadia ; Naeem, Naila ; Iftikhar, Aleesha ; Kamran, Muhammad ; Iftikhar, Ramsha ; Jamil, Nazia

Well-known Betti bases are the products obtained by the one-pot multicomponent reaction of 1-naphthol/2-naphthol, aliphatic/aromatic aldehydes, and secondary amines, and this reaction is known as the Betti reaction. During recent years, due to the unveiling of the pharmacological and synthetic potential of Betti bases, a tremendous increase in the studies reporting novel synthetic methods for the efficient synthesis of Betti bases was observed. This review presents the recent key developments in the green synthesis of the Betti bases and accounts for the significant number of the literature reported during 2019-2022. Both catalyst free as well as the catalyst promoted synthesis (nanocatalyst, biocatalyst, transition metal catalyst, etc.) along with the synthetic applications (catalyst, ligands/chiral auxiliaries, and valuable synthons), optoelectronic applications (fluorescence sensors for phosgene gas, Hg²⁺, and Cr³⁺ detection, quasi-reversible redox potential) and biological properties (anticancer agents, antioxidant, anti-inflammatory agents, antitubercular agents, pesticidal agents, anti-Alzheimer agents, Topoisomerase I inhibitors, YAP-TEAD interaction inhibitors, and DNA binding and cleavage activity) are discussed. There is a surge of interest for the development of the green and efficient Betti reaction for the construction of C-C and C-N bond in a single-step reaction accessing Betti bases as products. Along with key methodological developments for the green synthesis of Betti bases, their applications in synthetic organic chemistry, optoelectronic sensors, advanced materials synthesis, agrochemicals and pharmaceutically active scaffolds, during the period of 2019-2022, have been considered.

01 Oct 2019·Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchQ3 · BIOLOGY

Elevated cyclic-AMP represses expression of exchange protein activated by cAMP (EPAC1) by inhibiting YAP-TEAD activity and HDAC-mediated histone deacetylation

Q3 · BIOLOGY

Article

Author: McNeill, Madeleine C ; Wray, Jason P ; Newby, Andrew C ; Smith, Sarah A ; Ford, Kerrie L ; Ebrahimighaei, Reza ; Bond, Mark

Ligand-induced activation of Exchange Protein Activated by cAMP-1 (EPAC1) is implicated in numerous physiological and pathological processes, including cardiac fibrosis where changes in EPAC1 expression have been detected. However, little is known about how EPAC1 expression is regulated. Therefore, we investigated regulation of EPAC1 expression by cAMP in cardiac fibroblasts. Elevation of cAMP using forskolin, cAMP-analogues or adenosine A2B-receptor activation significantly reduced EPAC1 mRNA and protein levels and inhibited formation of F-actin stress fibres. Inhibition of actin polymerisation with cytochalasin-D, latrunculin-B or the ROCK inhibitor, Y-27632, mimicked effects of cAMP on EPAC1 mRNA and protein levels. Elevated cAMP also inhibited activity of an EPAC1 promoter-reporter gene, which contained a consensus binding element for TEAD, which is a target for inhibition by cAMP. Inhibition of TEAD activity using siRNA-silencing of its co-factors YAP and TAZ, expression of dominant-negative TEAD or treatment with YAP-TEAD inhibitors, significantly inhibited EPAC1 expression. However, whereas expression of constitutively-active YAP completely reversed forskolin inhibition of EPAC1-promoter activity it did not rescue EPAC1 mRNA levels. Chromatin-immunoprecipitation detected a significant reduction in histone3-lysine27-acetylation at the EPAC1 proximal promoter in response to forskolin stimulation. HDAC1/3 inhibition partially reversed forskolin inhibition of EPAC1 expression, which was completely rescued by simultaneously expressing constitutively active YAP. Taken together, these data demonstrate that cAMP downregulates EPAC1 gene expression via disrupting the actin cytoskeleton, which inhibits YAP/TAZ-TEAD activity in concert with HDAC-mediated histone deacetylation at the EPAC1 proximal promoter. This represents a novel negative feedback mechanism controlling EPAC1 levels in response to cAMP elevation.

Anti-Cancer Drugs

Transcriptional regulation of CYR61 and CTGF by LM98: a synthetic YAP-TEAD inhibitor that targets in-vitro vasculogenic mimicry in glioblastoma cells

Article

Author: Veilleux, Carolane ; Paquin, Alexis ; Gagnon, Alexandre ; Roy, Marie-Eve ; Annabi, Borhane

Glioblastoma (GBM) is a highly angiogenic malignancy of the central nervous system that resists standard antiangiogenic therapy, in part because of an alternative process to angiogenesis termed vasculogenic mimicry. Intricately linked to GBM, dysregulation of the Hippo signaling pathway leads to overexpression of YAP/TEAD and several downstream effectors involved in therapy resistance. Little is known about whether vasculogenic mimicry and the Hippo pathway intersect in the GBM chemoresistance phenotype. This study seeks to investigate the expression patterns of Hippo pathway regulators within clinically annotated GBM samples, examining their involvement in vitro regarding vasculogenic mimicry. In addition, it aims to assess the potential for pharmacological targeting of this pathway. In-silico analysis of the Hippo signaling members YAP1, TEAD1, AXL, NF2, CTGF, and CYR61 transcript levels in low-grade GBM and GBM tumor tissues was done by Gene Expression Profiling Interactive Analysis. Gene expression was analyzed by real-time quantitative PCR from human U87, U118, U138, and U251 brain cancer cell lines and in clinically annotated brain tumor cDNA arrays. Transient gene silencing was performed with specific small interfering RNA. Vasculogenic mimicry was assessed using a Cultrex matrix, and three-dimensional capillary-like structures were analyzed with Wimasis. CYR61 and CTGF transcript levels were elevated in GBM tissues and were further induced when in-vitro vasculogenic mimicry was assessed. Silencing of CYR61 and CTGF, or treatment with a small-molecule TEAD inhibitor LM98 derived from flufenamic acid, inhibited vasculogenic mimicry. Silencing of SNAI1 and FOXC2 also altered vasculogenic mimicry and reduced CYR61/CTGF levels. Pharmacological targeting of the Hippo pathway inhibits in-vitro vasculogenic mimicry. Unraveling the connections between the Hippo pathway and vasculogenic mimicry may pave the way for innovative therapeutic strategies.

100 Deals associated with YAP-TEAD inhibitor(Children's Medical Center Corp)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	-	The Children's Medical Center Corp.	14 Jul 2022

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YAP-TEAD inhibitor(Children's Medical Center Corp)

Overview

Basic Info

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R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

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