| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
| Targets |
TDI-011536 targets Lats kinase, a key component of the Hippo signaling pathway. Lats kinase phosphorylates and inactivates Yap (Yes-associated protein), a transcriptional co-activator that promotes cell proliferation and survival. By inhibiting Lats kinase, TDI-011536 prevents Yap phosphorylation, allowing Yap to translocate to the nucleus and activate target genes involved in cell proliferation and tissue regeneration. This mechanism makes the compound valuable for studying organ regeneration and repair.
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| ln Vitro |
In human propulsion organoids, TDI-011536 (3 μM; 24 hours) decreases Yap phosphorylation and (3 μM; 5 days) increases Müller astrocyte proliferation [1].
In vitro, TDI-011536 (3 µM; 24 h) reduces Yap phosphorylation and (3 µM; 5 days) induces proliferation of Müller glia in human retinal organoids. The compound inhibits Lats kinase activity, leading to Yap activation and downstream transcriptional responses. In cell-based assays, TDI-011536 promotes cell proliferation in various cell types including cardiac muscle cells and Müller glia. These in vitro activities demonstrate the compound's potential for promoting tissue regeneration. |
| ln Vivo |
TDI-011536 (200 mg/kg; intraperitoneal; once) lowers pYap levels in all three organs for at least 4 hours following injection and offers prolonged inhibition in the skin, heart, and heart over a 4-hour period [1]. Cardiomyocytes exhibit proliferative effects when exposed to TDI-011536 (100 mg/kg; intraperitoneal injection; once daily for 2 or 3 days) [1].
In vivo, TDI-011536 (200 mg/kg; i.p.; once) provides over 4 hours of Lats inhibition in the liver, heart, and skin and reduces pYap levels for at least 4 hours after injection in all three organs. TDI-011536 (100 mg/kg; i.p.; once daily for 2 or 3 days) shows a proliferative effect on cardiomyocytes. These studies demonstrate the compound's ability to inhibit Lats and promote cell proliferation in vivo, supporting its potential for organ regeneration research. |
| Enzyme Assay |
In vitro kinase assays are used to characterize TDI-011536's inhibitory activity against Lats kinase. The compound is incubated with purified Lats kinase and ATP substrate, and kinase activity is measured by phosphorylation of a peptide substrate. IC50 values are determined from dose-response curves. Yap phosphorylation is assessed by Western blot using phospho-specific antibodies in cells treated with the compound.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: human retinal Organoids Tested Concentrations: 3 µM Incubation Duration: 24 hrs (hours), 5 days Experimental Results: Inhibited Yap phosphorylation and promoted Müller glial cell proliferation. Cell-based assays for TDI-011536 are conducted in various cell types including cardiac muscle cells, Müller glia, and other relevant cell lines. Cells are treated with the compound at concentrations such as 3 µM for 24 hours to 5 days. Yap phosphorylation is assessed by Western blot. Cell proliferation is measured by BrdU incorporation, EdU labeling, or cell counting. Retinal organoid assays are used to assess Müller glia proliferation. |
| Animal Protocol |
Animal/Disease Models: Live mice (immediate immunoblot analysis of heart, liver and skin) after injection) [1].
Doses: 200 mg/kg Route of Administration: intraperitoneal (ip) injection; once. Experimental Results: pYap amounts were diminished for at least 4 hrs (hrs (hours)) after injection in all three organs, with levels returning to control values within a day. Animal/Disease Models: 8weeks old male mice (frozen model) [1]. Doses: 100 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 2 or 3 days Experimental Results: Promote cardiomyocyte proliferation. In vivo animal experiments with TDI-011536 are conducted in mouse models. The compound is administered intraperitoneally at doses of 100-200 mg/kg. For acute studies, a single dose is given and tissues are harvested at various time points (e.g., 4 hours post-injection) for analysis of Lats inhibition and Yap phosphorylation. For proliferation studies, the compound is administered daily for 2-3 days. Tissues are analyzed for cell proliferation markers. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of TDI-011536 include solubility in DMSO: 73 mg/mL (200.31 mM). For in vivo administration, formulations include 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline or CMC-Na suspension. Storage: powder at -20°C for 3 years; in solvent at -80°C for 1 year. Specific PK parameters such as half-life, Cmax, and bioavailability have not been extensively reported.
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| Toxicity/Toxicokinetics |
Safety and toxicology data for TDI-011536 are limited. The compound is for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling the compound. The compound should be stored properly and disposed of in accordance with applicable regulations.
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| References | |
| Additional Infomation |
TDI-011536 has CAS number 2687970-96-1, molecular formula C19H16N4O2S, and molecular weight 364.42. IUPAC name: (Z)-N-(3-benzyl-4-(hydroxymethyl)thiazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide. It is a potent Lats kinase inhibitor that interrupts Hippo-Yap signaling and promotes proliferation of lesioned cardiac muscle cells. Purity: ≥98%. Storage: powder at -20°C for 3 years; in solvent at -80°C for 1 year. Not for human use; for research purposes only.
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| Molecular Formula |
C19H16N4O2S
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|---|---|
| Molecular Weight |
364.42
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| Exact Mass |
364.099
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| CAS # |
2687970-96-1
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| PubChem CID |
156824399
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
588
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(=O)/N=C2\SC=C(CO)N\2CC2=CC=CC=C2)=CN=C2NC=CC=C12
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| InChi Key |
LJNPGPUDPDQGLE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16N4O2S/c24-11-14-12-26-19(23(14)10-13-5-2-1-3-6-13)22-18(25)16-9-21-17-15(16)7-4-8-20-17/h1-9,12,24H,10-11H2,(H,20,21)
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| Chemical Name |
N-[3-benzyl-4-(hydroxymethyl)-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 : ~125 mg/mL (~343.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.71 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.71 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7441 mL | 13.7204 mL | 27.4409 mL | |
| 5 mM | 0.5488 mL | 2.7441 mL | 5.4882 mL | |
| 10 mM | 0.2744 mL | 1.3720 mL | 2.7441 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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