| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
LATS1 and LATS2 (large tumor suppressor kinases 1 and 2), which are key negative regulators of the Hippo‑YAP signaling pathway. NIBR-LTSi is a selective LATS kinase inhibitor.
|
|---|---|
| ln Vitro |
In cell‑free kinase assays, NIBR-LTSi inhibits LATS kinase activity with an IC50 of 1.4 nM in a biochemical CALIPER assay. It robustly reduces YAP phosphorylation, increases proliferation in HEK293A cells, and promotes primary keratinocyte expansion while blocking differentiation in a human 3D skin model. It also promotes liver and kidney organoid formation.
|
| ln Vivo |
In vivo, NIBR-LTSi is orally active and expands organoids derived from several mouse and human tissues. It promotes intestinal stem cell expansion, blocks their differentiation, accelerates liver regeneration following hepatectomy, and induces YAP/TAZ‑dependent hepatocyte proliferation, demonstrating strong tissue regenerative potential.
|
| Enzyme Assay |
A general cell‑free protocol for LATS kinase inhibition: A radiometric or time‑resolved fluorescence resonance energy transfer (TR‑FRET) assay is used. Recombinant LATS1 (5 nM) is incubated with a biotinylated YAP peptide substrate (1 uM) and ATP (10 uM) in kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT) with varying concentrations of NIBR-LTSi (0.01‑1000 nM). After 60 minutes at 30degC, the reaction is stopped with EDTA, and phosphorylated product is detected. IC50 is calculated.
|
| Cell Assay |
A general cellular protocol for NIBR-LTSi: HEK293A cells are seeded in 12‑well plates. Cells are treated with NIBR-LTSi at concentrations of 0.1, 1, 5, 10, 25 uM for 24‑48 hours. YAP phosphorylation (Ser127) and total YAP levels are assessed by Western blot. Cell proliferation is measured by EdU incorporation assay. For organoid studies, mouse intestinal crypts are cultured in Matrigel and treated with NIBR-LTSi (0.1‑10 uM) for 7‑14 days, and organoid formation efficiency is quantified.
|
| Animal Protocol |
General animal protocol for NIBR-LTSi: Male C57BL/6J mice undergo 70% partial hepatectomy (PHx) to induce liver regeneration. NIBR-LTSi is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween‑80, 45% saline) and administered via oral gavage at doses of 10, 30, and 100 mg/kg once daily for 3‑7 days. Liver weight/body weight ratio is calculated, and hepatocyte proliferation is assessed by Ki‑67 immunohistochemistry and EdU labeling.
|
| ADME/Pharmacokinetics |
General PK protocol for NIBR-LTSi: NIBR-LTSi is orally active with good bioavailability. Male Sprague‑Dawley rats are administered NIBR-LTSi via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg). Blood samples are collected over 24 hours. Plasma concentrations are quantified by LC‑MS/MS. PK parameters (Cmax, Tmax, AUC, t1/2, clearance, Vd, oral bioavailability) are calculated.
|
| Toxicity/Toxicokinetics |
General toxicity protocol for NIBR-LTSi: A 28‑day repeat‑dose oral toxicity study is performed in Sprague‑Dawley rats. NIBR-LTSi is administered at doses of 5, 25, and 100 mg/kg/day. Parameters include clinical signs, body weight, food consumption, ophthalmology, hematology (CBC, differential), serum chemistry (ALT, AST, BUN, creatinine), and histopathology of major organs (liver, kidney, spleen, lung, heart, gastrointestinal tract).
|
| References | |
| Additional Infomation |
NIBR-LTSi has a molecular formula of C18H20N4O and a molecular weight of 308.39 g/mol. It was identified and characterized by Namoto K, et al. (Cell Stem Cell. 2024;31(4):554‑569.e17). By activating YAP signaling, NIBR-LTSi promotes tissue regeneration in multiple organs, including the liver, intestine, and kidney, representing a novel regenerative medicine approach.
|
| Molecular Formula |
C18H20N4O
|
|---|---|
| Molecular Weight |
308.38
|
| Appearance |
Solid powder
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 2 mg/mL (6.49 mM; with sonication (<60°C))
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2428 mL | 16.2138 mL | 32.4275 mL | |
| 5 mM | 0.6486 mL | 3.2428 mL | 6.4855 mL | |
| 10 mM | 0.3243 mL | 1.6214 mL | 3.2428 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
