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Chemical Structure| 1424635-83-5 Chemical Structure| 1424635-83-5

Structure of TRULI
CAS No.: 1424635-83-5

Chemical Structure| 1424635-83-5

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TRULI (Lats-IN-1) is a potent, ATP-competitive inhibitor of Lats1 and Lats2 kinases, promoting Yap-dependent proliferation in postmitotic mammalian tissue.

Synonyms: Lats-IN-1;LATS Inhibitor 1

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Artioli, Annasara ; Gasparotto, Matteo ; Rossetti, Andrea Carlo ; Hass, Yannick ; Hoffrichter, Anne ; Wimmer, Ryszard , et al.

Abstract: Basal radial glia (bRG) drive human cortical expansion but remain underrepresented in vitro. We established a defined and expandable 2D system for efficient generation of human bRG from iPSCs. These cells recapitulate canonical molecular signatures, hallmark somal translocation behaviours, intrinsic differentiation potential, and integration into organoid tissue. Network-based analyses identified PAK2 as a regulator of mitotic somal translocation, illustrating the system’s utility for mechanistic interrogation of bRG biology.

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Nie, Li ; Fei, Chenjie ; Fan, Yizeng ; Dang, Fabin ; Zhao, Ziyue ; Zhu, Tingfang , et al.

Abstract: NLRP3 inflammasome activation, essential for cytokine secretion and pyroptosis in response to diverse stimuli, is closely associated with various diseases. Upon stimulation, NLRP3 undergoes subcellular membrane trafficking and conformational rearrangements, preparing itself for inflammasome assembly at the microtubule-organizing center (MTOC). Here, we elucidate an orchestrated mechanism underlying these ordered processes using human and murine cells. Specifically, NLRP3 undergoes palmitoylation at two sites by palmitoyl transferase zDHHC1, facilitating its trafficking between subcellular membranes, including the mitochondria, trans-Golgi network (TGN), and endosome. This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. Consistently, Zdhhc1-deficiency mitigated LPS-induced inflammation and conferred protection against mortality in mice. Altogether, our findings provide valuable insights into the regulation of NLRP3 membrane trafficking and inflammasome activation, governed by palmitoylation and phosphorylation events.

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Li, Yijian ; Ge, Lingling ; Ren, Bangqi ; Zhang, Xue ; Yin, Zhiyuan ; Liu, Hongling , et al.

Abstract: Purpose: Regeneration after tissue injury is often associated with cell fate plasticity, which restores damaged or lost cells. Here, we examined the de-differentiation of corneal epithelial cells (CECs) into functional limbal epithelial stem cells (LESCs) after the ablation of innate stem cells. Methods: The regeneration of LESCs after the ablation of innate LESCs was identified by a set of markers: ApoE+/Cx43low/CK12. CK14-CreERT2 or Slc1a3-CreERT mice were crossed with reporter mice to trace the fate of CECs. YAP-TEAD inhibitor verteporfin (VTP) and LATS inhibitor TRULI were used to examine the role of Hippo/YAP pathway in the de-differentiation of CECs. Results: LESCs-ablation cornea showed to be functionally normal, including the maintenance of corneal transparency, prevention of conjunctivalization, and wound healing rate equivalent to that of normal cornea. ApoE+/Cx43low/CK12 LESCs regenerated at the limbus at 6 days after the ablation of innate stem cells, and maintained for at least 6 months. Corneal epithelial lineage tracing showed that CECs migrated back to the limbus after the ablation of innate stem cells, and de-differentiated into active and quiescent LESCs (aLESCs and qLESCs), which participated in corneal epithelial homeostasis and wound healing, respectively, like their innate counterparts. However, when the limbus niche was destroyed by NaOH (1 M, 5 seconds), CECs that occupied the limbus could not de-differentiate into ApoE+/Cx43low/CK12 LESCs and cornea developed into conjunctivalization. In addition, the protein level and activity of YAP increased at the early stage (1–2 days) after the ablation of limbal epithelium, and decreased when the de-differentiation occurred. The YAP-TEAD inhibitor VTP promoted the de-differentiation, whereas LATS inhibitor TRULI inhibited the de-differentiation of CECs. However, the persistent activation of YAP prevented the de-differentiation of CECs after an additional NaOH burn to the limbal stroma, and VTP could not rescue the capacity of CECs to de-differentiate into LESCs. Conclusions: These results reveal the de-differentiation of CECs into functional LESCs after the ablation of innate stem cells, and suggest potential role of Hippo/YAP pathway in the de-differentiation of CECs in vivo.

Keywords: limbal epithelial stem cells ; de-differentiation ; limbal niche ; Hippo/YAP

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Li, Yijian ; Ge, Lingling ; Ren, Bangqi ; Zhang, Xue ; Yin, Zhiyuan ; Liu, Hongling , et al.

Abstract: Regeneration after tissues injury is often associated with cell fate plasticity, which restores damaged or lost cells. The de-differentiation of corneal epithelial cells (CECs) into functional stem cells after the ablation of innate stem cells, known as limbal epithelial stem cells (LESCs), remains controversial. In this study, we showed the functional maintenance of corneal epithelium after the ablation of innate stem cells, and the regeneration of functional LESCs, which maintained corneal transparency, prevented corneal conjunctivalization and participated in the wound healing. Subsequent intravital lineage tracing revealed that CECs could de-differentiate into active or quiescent LESCs, which functioned as well as their innate counterparts. Furthermore, the de-differentiation of CECs required an intact limbal niche, and the outcome of the competition between conjunctival and corneal epithelium for the limbal niche determined whether the de-differentiation would occur or not. Mechanically, the suppression of YAP signal promoted the de-differentiation of CECs after the ablation of innate stem cells, while the persistent activation of YAP prevented the de-differentiation of CECs after an additional alkali burn to the limbal stroma. These results will pave the way for an alternative approach to treat limbal stem cell deficiency (LSCD) by modulating the de-differentiation of CECs in vivo.

Keywords: Limbal epithelial stem cells ; De-differentiation ; Limbal niche ; YAP

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Hile, Grace A ; Coit, Patrick ; Xu, Bin ; Victory, Amanda M ; Gharaee‐Kermani, Mehrnaz ; Estadt, Shannon N , et al.

Abstract: Objective: Photosensitivity is one of the most common manifestations of systemic lupus erythematosus (SLE), yet its pathogenesis is not well understood. The normal-appearing epidermis of patients with SLE exhibits increased ultraviolet B (UVB)–driven cell death that persists in cell culture. Here, we investigated the role of epigenetic modification and Hippo signaling in enhanced UVB-induced apoptosis seen in SLE keratinocytes. Methods: We analyzed DNA methylation in cultured keratinocytes from SLE patients compared to keratinocytes from healthy controls (n = 6/group). Protein expression was validated in cultured keratinocytes using immunoblotting and immunofluorescence. An immortalized keratinocyte line overexpressing WWC1 was generated via lentiviral vector. WWC1-driven changes were inhibited using a large tumor suppressor kinase 1/2 (LATS1/2) inhibitor (TRULI) and small interfering RNA (siRNA). The interaction between the Yes-associated protein (YAP) and the transcriptional enhancer associate domain (TEAD) was inhibited by overexpression of an N/TERT cell line expressing a tetracycline-inducible green fluorescent protein–tagged protein that inhibits YAP–TEAD binding (TEADi). Apoptosis was assessed using cleaved caspase 3/7 and TUNEL staining. Results: Hippo signaling was the top differentially methylated pathway in SLE versus control keratinocytes. SLE keratinocytes (n = 6) showed significant hypomethylation (Δβ = −0.153) and thus overexpression of the Hippo regulator WWC1 (P = 0.002). WWC1 overexpression increased LATS1/2 kinase activation, leading to YAP cytoplasmic retention and altered proapoptotic transcription in SLE keratinocytes. Accordingly, UVB-mediated apoptosis in keratinocytes could be enhanced by WWC1 overexpression or YAP–TEAD inhibition, mimicking SLE keratinocytes. Importantly, inhibition of LATS1/2 with either the chemical inhibitor TRULI or siRNA effectively eliminated enhanced UVB-apoptosis in SLE keratinocytes. Conclusion: Our work unravels a novel driver of photosensitivity in SLE: overactive Hippo signaling in SLE keratinocytes restricts YAP transcriptional activity, leading to shifts that promote UVB apoptosis.

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de Medeiros, Gustavo ; Ortiz, Raphael ; Strnad, Petr ; Boni, Andrea ; Moos, Franziska ; Repina, Nicole , et al.

Abstract: Organoids provide an accessible in vitro system to mimic the dynamics of tissue regeneration and development. However, long-term live-imaging of organoids remains challenging. Here we present an experimental and image-processing framework capable of turning long-term light-sheet imaging of intestinal organoids into digital organoids. The framework combines specific imaging optimization combined with data processing via deep learning techniques to segment single organoids, their lumen, cells and nuclei in 3D over long periods of time. By linking lineage trees with corresponding 3D segmentation meshes for each organoid, the extracted information is visualized using a web-based “Digital Organoid Viewer” tool allowing combined understanding of the multivariate and multiscale data. We also show backtracking of cells of interest, providing detailed information about their history within entire organoid contexts. Furthermore, we show cytokinesis failure of regenerative cells and that these cells never reside in the intestinal crypt, hinting at a tissue scale control on cellular fidelity.

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Calle, Ana Maria Low ;

Abstract: The p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cancers, while its expression is often repressed in breast cancers. In the canonical conserved Hippo pathway, known to play a complex role in regulating the growth of cancer cells, the protein kinases Mammalian Ste20 like kinases 1/2 (MST) and Large tumor suppressor kinases 1/2 (LATS) act sequentially to phosphorylate and inhibit the Yes-associated Protein/Transcriptional coactivator PDZ binding transcription factors (YAP/TAZ). We found that in the MCF10A mammary epithelial cell line and in squamous and breast cancer cell lines, expression of deltaNp63 RNA and protein is strongly repressed by inhibition of specific components of the Hippo pathway in a manner that is independent of p53. While the Hippo pathway protein kinases MST1/2 and LATS1 are required for p63 expression, the next step of the pathway namely phosphorylation and degradation of the YAP/TAZ transcriptional activators, is not required for repression of p63. This suggests that regulation of p63 expression occurs by a non-canonical version of the Hippo pathway. Interestingly, we observed that experimentally lowering p63 expression leads to increased Yes Associated Protein protein levels, thereby constituting a feedback loop. In addition, p63 loss reduces the growth of MCF10A and squamous cancer cell lines. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells.

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Ramírez Cuéllar, Angélica Julieta ;

Abstract: In this Thesis we report the successful growth of hormone responsive T47D cells as 3D spheroids in Matrigel mimicking the ECM. A detailed characterization by using a genome-wide approach of the main physical and biochemical differences between cells cultured in conventional 2D and as 3D spheroids, focusing on the particular pathways regulated through mechano-transductional signaling. In the first two chapters, the main physical and genomic differences are detailed. 3D grown cells have a rounder nucleus with less accessible and more compacted chromatin, impacting on the regulation of over 2000 genes. Gene topology was by HiC, results indicate that 3D cells exhibit a subtle trend towards enrichment in regions belonging to the B compartment, a decrease on chromatin bound architectural protein CTCF and increased TAD fusion. In the third chapter we discuss the involvement of the Hippo pathway, involved in mechanosensing in 3D grown cells. In line with the observed p-LATS mediated phosphorylation of CTCF promoting its displacement from chromatin. Regarding hormone regulation, 3D grown cells respond more efficiently and exhibit an increase in PR binding sites leading to chromatin remodeling and to a higher number of regulated genes. Our results suggest that ECM exerts important effects on the structure and function of the breast cancer cell nucleus.

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Alternative Products

Product Details of TRULI

CAS No. :1424635-83-5
Formula : C18H14N4OS
M.W : 334.40
SMILES Code : O=C(C1=CNC2=NC=CC=C21)/N=C3SC=CN\3CC4=CC=CC=C4
Synonyms :
Lats-IN-1;LATS Inhibitor 1
English Name :N-(3-Benzylthiazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide
MDL No. :MFCD33402276
InChI Key :VTXBMVZVPUSAJF-UHFFFAOYSA-N
Pubchem ID :71890885

Safety of TRULI

Related Pathways of TRULI

Hippo

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
SLE keratinocytes 10 µM 24 hours Inhibition of LATS1/2 kinase activity, reducing UVB-induced apoptosis Arthritis Rheumatol. 2023 Jul;75(7):1216-1228.
Human retinal organoids 10 µM 24 hours To test the inhibitory effect of TRULI on Yap phosphorylation in human retinal organoids, showing a significant 30% reduction in Yap phosphorylation. Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2206113119.
Human embryonic stem cells (hESCs) 10 µM 24 hours TRULI inhibits YAP phosphorylation, enhances YAP nuclear localization, and promotes the differentiation of non-neural ectoderm (NNE). Elife. 2022 Apr 22;11:e73075.
Chondrocytes 10, 25, 50 µM 48 hours TRULI restored IL-1β-induced reduction in ECM synthesis and blocked abnormal ECM degradation by inhibiting LATS1 phosphorylation Bone Res. 2025 Mar 12;13(1):33.
K562 cells 30 µM or greater 48 hours TRULI significantly reduced the clonogenicity, migratory capacity, and ROS production of K562 cells, indicating its inhibition of the tumorigenic properties of CML cells. Sci Rep. 2024 Feb 18;14(1):3993.
Neural crest (NC) cells 10 µM TRULI treatment resulted in the complete loss of neural crest (NC) cells and a significant increase in the expression of the epidermal marker KRT18. Elife. 2022 Apr 22;11:e73075.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice CK14-CreERT2 or Slc1a3-CreERT mice Ocular surface administration 20 μM Every 8 hours for 4 consecutive days TRULI inhibited the de-differentiation of CECs, indicating the important role of the Hippo/YAP pathway in the de-differentiation of CECs. Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):32
Mice Cardiac cryolesion model Intraperitoneal injection 200 mg/kg Single injection, lasting 4 hours To test the inhibitory effect of TDI-011536 on Yap phosphorylation in mice, showing a significant reduction in Yap phosphorylation in the heart, liver, and skin, with the effect lasting 4 hours. Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2206113119.
Mice DMM-induced osteoarthritis model Intra-articular injection 5 mg/mL Twice a week for 8 weeks TRULI improved abnormal behavior post-DMM surgery, reduced cartilage degeneration, and restored ECM balance Bone Res. 2025 Mar 12;13(1):33.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.99mL

0.60mL

0.30mL

14.95mL

2.99mL

1.50mL

29.90mL

5.98mL

2.99mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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