Cellules souches

Potent oral TEAD-YAP/TAZ inhibitor-2 with 3 nM EC50; exhibits anti-proliferative and antitumor effects.

BAY 593 functions as an inhibitor of geranylgeranyltransferase-I (GGTase-I), effectively preventing the activation of Rho-GTPases and consequently inactivating YAP1/TAZ signaling pathways. It has been shown to inhibit tumor growth dose-dependently in xenograft mouse models, exhibiting IC50 values of 38.4 nM in MT-1080 cells and 564 nM in MDA-MB-231 cells, as well as in PXF 541 xenografts.

pan-TEAD-IN-1 (Compound 3) is an orally active pan-inhibitor of TEAD, disrupting its interaction with coactivators YAP/TAZ by targeting the palmitoylation site of TEAD. This inhibition leads to the downregulation of oncogene transcription, such as Ctgf and Cyr61, within the Hippo signaling pathway. Demonstrating outstanding efficacy, pan-TEAD-IN-1 has an IC50 of 0.36 nM for luciferase and 1.52 nM for H226 cells, along with favorable pharmacokinetic properties (AUC0–∞= 228.7 μg/mL·min, T1/2= 183.9 min). The compound significantly inhibits tumor growth in xenograft models of TEAD-dependent cancers, indicating its potential for research in these cancer types.

PF-06952229 is a selective inhibitor of TGFβRI. PF-06952229 can be used in studies about the treatment of solid tumors, specifically metastatic breast cancer.

CJJ300 is a TGF-β inhibitor disrupting TGF-β-TβR complex formation, with an IC50 of 5.3 μM, and halts cell migration.

TEAD-IN-2 is a potent and bifunctional TEAD inhibitor to induce TEAD protein degradation via the ubiquitination pathway, with anticancer potential.

VT103, an oral TEAD1 palmitoylation inhibitor, shows promise against various cancers by disrupting YAP/TAZ-TEAD interactions.

JA310 is a highly selective inhibitor of the MST3 kinase, demonstrating significant cellular potency with an EC50 value of 106 nM [1].

TEAD-IN-6 (Example 11-1) is a TEAD modulator that inhibits the YAP1/TAZ-TEAD interaction, and has applications in cancer research [1].

Chromenone 1 is a potent potentiator of osteogenic bone morphogenetic protein (BMP).

SIS3 free base is a potent and selective Smad3 phosphorylation inhibitor. SIS3 free base inhibits the myofibroblast differentiation of fibroblasts by TGF-β1.

AF-2112, a TEAD inhibitor derived from Flufenamic acid, significantly diminishes the expression of CTGF, Cyr61, Axl, and NF2.

DMH2 is a selective BMP type I receptor (ALK2/ALK3) inhibitor. DMH2 inhibits the proliferation of lung cancer cell lines and induces cell death.

SJ000063181 activates BMP signaling (EC50 ≤1μM), usable as probe in zebrafish embryos.

LM-41 is a TEAD binding agent with potential anticancer activity for the study of breast cancer.

LEQ506 is a Smo inhibitor with IC50s of 2 nM and 4 nM for hSmo and mSmo, respectively.

IHMT-MST1-58 is a STE20-like protein 1 kinase (MST1) inhibitor (IC50:23 nM) with high efficiency, selectivity and oral activity.

MSC-4106, an oral YAP/TAZ-TEAD inhibitor, blocks TEAD1/3 auto-palmitoylation and suppresses NCI-H226 tumors.

TT-10 (TAZ-K) activates YAP-TEAD; useful in heart disease with cardiomyocyte loss research.

TM2 TEAD inhibitor, a robust and reversible inhibitor of the TEA domain transcription factor, presents dual inhibitory concentrations (IC50) of 38 nM for TEAD4