| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
TRULI targets Lats1 and Lats2 (Large Tumor Suppressor Kinases 1 and 2), which are key negative regulators of the Hippo signaling pathway. By inhibiting Lats1 and Lats2, TRULI prevents the phosphorylation of YAP (Yes-associated protein), allowing YAP to translocate to the nucleus and activate transcription of genes involved in cell proliferation and survival. TRULI acts as an ATP-competitive inhibitor of Lats kinases, effectively blocking their kinase activity and activating the YAP signaling pathway.
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| ln Vitro |
The IC50 of TRuLI increases with ATP concentration [1]. TRuLI (10 μM; 24 hours) interferes with the ability of Lats kinase to phosphorylate Yap with an EC50 of 510 nM [1]. TRuLI causes Yap-dependent proliferation of Müller glia in the mouse inner ear, mouse cardiomyocytes, and human Sertoli cells in retinal organoids [1]. TRuLI promotes G1-S and G2-M checkpoint switching and generates supporting cells capable of transdifferentiation [1].
TRULI inhibits both Lats1 and Lats2 with an IC50 of 0.2 nM. It suppresses Yap phosphorylation and induces cell proliferation in several cell lines and tissues. In serum-starved HEK293A cells, TRULI inhibits YAP1 phosphorylation with an EC50 of 510 nM. These findings demonstrate the compound's potent activity as a Lats kinase inhibitor and YAP pathway activator. TRULI's ability to induce proliferation in various cell types makes it a valuable tool for studying Hippo signaling and regeneration. |
| ln Vivo |
TRULI promotes the initial stages of proliferative regeneration of sensory receptors in the inner ear. It also promotes Yap-dependent proliferation in postmitotic mammalian tissues. These in vivo activities highlight the compound's potential for studying tissue regeneration and repair. TRULI's ability to activate YAP signaling by inhibiting Lats kinases makes it a valuable tool for investigating the role of the Hippo pathway in regeneration, development, and disease. Further research is needed to explore its therapeutic potential.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for TRULI typically involves a kinase activity assay using recombinant Lats1 or Lats2 proteins. The kinase is incubated with ATP and a peptide substrate in the presence of varying concentrations of TRULI. The incorporation of phosphate into the substrate is measured using radioactive (e.g., 33P-ATP) or fluorescence-based detection methods. The IC50 is calculated from the inhibition curve. Alternatively, a competition binding assay can be performed to measure the compound's affinity for the ATP-binding pocket.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: MCF 10A cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished the phosphorylation of Yap at residue S127. The in vitro cellular assay for TRULI typically uses HEK293A cells or other cell lines to measure YAP phosphorylation. Cells are serum-starved to reduce baseline YAP phosphorylation and treated with varying concentrations of TRULI. YAP phosphorylation is measured by Western blot using phospho-specific antibodies (e.g., phospho-YAP Ser127). The EC50 for inhibition of YAP phosphorylation is calculated. Cell proliferation assays, such as BrdU incorporation or cell counting, can be used to assess the compound's effects on cell growth. |
| Animal Protocol |
In vivo animal studies for TRULI typically involve models of tissue regeneration or injury. For example, the compound's effects on sensory receptor regeneration in the inner ear can be assessed in animal models of hearing loss. TRULI is administered via appropriate routes, and tissue sections are analyzed for proliferation markers and YAP activation. The compound's ability to promote proliferation in postmitotic tissues can be evaluated in various organ systems. Specific protocols depend on the biological question being addressed.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for TRULI are not extensively reported. The compound has a molecular weight of 334.40 and a formula of C18H14N4OS. It is soluble in DMSO at 67 mg/mL (200.35 mM). For in vivo administration, TRULI can be formulated as a homogeneous suspension in CMC-Na at ≥5 mg/mL for oral administration, or as a clear solution in 5% DMSO + Corn Oil at 3.350 mg/mL for injection. Specific ADME parameters are not detailed.
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| Toxicity/Toxicokinetics |
Toxicity data for TRULI are not available in the public domain. As a research compound, comprehensive toxicological evaluations have not been performed. The compound is intended for laboratory research use only and should be handled with standard safety precautions. Appropriate personal protective equipment should be worn when handling this compound. Consult the Material Safety Data Sheet for specific safety and handling information.
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| References | |
| Additional Infomation |
Truli is a pyrrolopyridine compound with the structure 1H-pyrrolo[2,3-b]pyridine, substituted at position 3 with an N-(3-benzyl-1,3-thiazolyl-2(3H)-ylidene)formamide group. It is a potent ATP-competitive inhibitor of LATS1 and LATS2 kinases and also an activator of the YAP signaling pathway. It is an EC 2.7.11.1 (nonspecific serine/threonine protein kinase) inhibitor. It belongs to the benzene, 1,3-thiazolyl, pyrrolopyridine, and enamide classes of compounds.
TRULI (Lats-IN-1) is a potent, ATP-competitive inhibitor of Lats1 and Lats2 kinases (IC50 = 0.2 nM) that activates the YAP signaling pathway. It suppresses Yap phosphorylation and induces cell proliferation in various cell lines and tissues. TRULI promotes proliferative regeneration of sensory receptors in the inner ear and Yap-dependent proliferation in postmitotic tissues. The compound is a valuable research tool for studying Hippo signaling, tissue regeneration, and development. TRULI is not in clinical trials and has not been approved for therapeutic use. |
| Molecular Formula |
C18H14N4OS
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| Molecular Weight |
334.39
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| Exact Mass |
334.088
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| CAS # |
1424635-83-5
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| PubChem CID |
71890885
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| Appearance |
White to light yellow solid powder
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| Density |
1.36±0.1 g/cm3
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
529
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)CN2C=CSC2=NC(=O)C3=CNC4=C3C=CC=N4
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| InChi Key |
VTXBMVZVPUSAJF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14N4OS/c23-17(15-11-20-16-14(15)7-4-8-19-16)21-18-22(9-10-24-18)12-13-5-2-1-3-6-13/h1-11H,12H2,(H,19,20)
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| Chemical Name |
N-(3-benzyl-1,3-thiazol-2-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (149.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9905 mL | 14.9526 mL | 29.9052 mL | |
| 5 mM | 0.5981 mL | 2.9905 mL | 5.9810 mL | |
| 10 mM | 0.2991 mL | 1.4953 mL | 2.9905 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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