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| Targets |
LDN-192960 targets Haspin kinase and DYRK2 (dual-specificity tyrosine-regulated kinase 2). Haspin is a mitotic serine/threonine kinase that plays a critical role in chromosome segregation by phosphorylating histone H3 at threonine 3 (H3T3) during mitosis. DYRK2 is a dual-specificity kinase involved in cell cycle regulation and apoptosis. By inhibiting these kinases, LDN-192960 interferes with kinase-mediated cell cycle regulatory signaling. The compound also inhibits CLK1 with an IC₅₀ of 0.21 μM. Its selectivity profile makes it a valuable tool for studying the roles of Haspin and DYRK2 in cell cycle progression and mitotic regulation.
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| ln Vitro |
Strictly speaking, only five kinases (IC50<1 μM) are effectively inhibited by LDN-192960 (10 μM). These five kinases are CLK1 (IC50=0.21 μM), DYRK1A (IC50= 0.10 μM), DYRK2 (IC50= 2 nM), DYRK3 (IC50= 19 nM), and PIM1 (IC50=0.72 μM) [1]. With an EC50 of 1.17 μM, LDN-0192960 (0-5 μM; 2 hours) reduces p-Thr3H3 levels in Haspin-overexpressing HeLa cells, exhibiting the classic Haspin inhibitory phenotype [2]. In mitotically synchronized HeLa cells, LDN-0192960 (0-1 μM; 1 hour incubation in the presence of nocodazole and MG132) reduced p-Thr3H3 levels with an EC50 of 0.02 μM, exhibiting a classic Haspin inhibitory phenotype [2].
In vitro, LDN-192960 potently inhibits Haspin with an IC₅₀ of 10 nM and DYRK2 with an IC₅₀ of 48 nM. At 10 μM, the compound shows selectivity, effectively inhibiting only five kinases with IC₅₀ <1 μM, including CLK1 (IC₅₀ = 0.21 μM). The compound is also used for imaging of thiols in live cells. These in vitro activities confirm its potent and selective kinase inhibition profile. Detailed cellular activity data, such as effects on cell cycle progression or phosphorylation of Haspin substrates, are not extensively reported in the available literature. |
| ln Vivo |
Detailed in vivo activity data for LDN-192960 are not extensively reported in the available literature. As a potent and selective Haspin/DYRK2 inhibitor, it is expected to have applications in studying cell cycle regulation and mitotic progression in vivo. The compound's ability to interfere with kinase-mediated cell cycle regulatory signaling suggests potential for studying its effects on tumor growth and cell proliferation in animal models. However, specific in vivo efficacy data are not provided in the available sources.
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| Enzyme Assay |
Non-cell-based enzyme assays for LDN-192960 typically involve in vitro kinase activity assays using purified recombinant Haspin or DYRK2 enzymes. The compound is incubated with the target kinase, a peptide substrate, and ATP at varying concentrations in a suitable buffer system. Kinase activity is measured by quantifying substrate phosphorylation using techniques such as radiometric detection (e.g., ³³P-ATP incorporation), fluorescence polarization, or ELISA-based detection. IC₅₀ values are determined from dose-response curves. Selectivity profiling against a panel of kinases is performed to confirm specificity.
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| Cell Assay |
Cellular assays for LDN-192960 are performed using various cell lines to assess its effects on cell cycle progression and mitotic regulation. Cells are treated with the compound at various concentrations, and endpoints such as histone H3 phosphorylation (H3T3), cell cycle distribution, and cell proliferation are measured. Phosphorylation of Haspin substrates is assessed by Western blotting using phospho-specific antibodies. Cell viability and proliferation are measured using standard assays such as MTT or CellTiter-Glo.
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| Animal Protocol |
In vivo animal models for LDN-192960 would be required to assess its therapeutic potential. Based on its mechanism as a Haspin/DYRK2 inhibitor, relevant models could include xenograft studies in immunodeficient mice bearing cancer cell lines. The compound would be administered via appropriate routes (e.g., oral gavage or intraperitoneal injection) at various doses. Tumor growth inhibition would be monitored over time. Pharmacodynamic markers such as histone H3 phosphorylation in tumor tissues would be assessed. Detailed protocols are not extensively reported in the available literature.
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| ADME/Pharmacokinetics |
LDN-192960 has a molecular weight of 328.43 g/mol (free base) and a molecular formula of C₁₈H₂₀N₂O₂S. The dihydrochloride salt has a molecular weight of 401.4 g/mol. CAS number is 184582-62-5. The compound is soluble in DMSO (30 mg/mL) and water (10 mg/mL). Purity is >98% by HPLC. Storage conditions: powder at -20°C for 3 years; in solvent at -80°C for 2 years. The compound is supplied as a solid powder for research use only.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for LDN-192960 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only and is not for human consumption. Given its mechanism of kinase inhibition, potential effects on cell cycle regulation and mitotic progression in normal tissues would be key safety considerations. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
LDN-192960 is also known as 3-[(2,7-dimethoxyacridin-9-yl)sulfanyl]propan-1-amine. It is a potent dual inhibitor of Haspin and DYRK2 with IC₅₀ values of 10 nM and 48 nM, respectively. The compound shows selectivity, inhibiting only five kinases at 10 μM (IC₅₀ <1 μM), including CLK1 (IC₅₀ = 0.21 μM). It interferes with kinase-mediated cell cycle regulatory signaling. The compound is used in research applications studying cell cycle regulation, mitosis, and kinase signaling. It is for research use only.
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| Molecular Formula |
C14H18N2O3S
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| Molecular Weight |
328.4286
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| Exact Mass |
328.124
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| CAS # |
184582-62-5
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| Related CAS # |
LDN-192960 hydrochloride;2309172-48-1
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| PubChem CID |
53390843
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| Appearance |
Yellow to orange solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
536.1±40.0 °C at 760 mmHg
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| Flash Point |
278.0±27.3 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.672
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| LogP |
3.52
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
23
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| Complexity |
343
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZFOMCSNUEHMROO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20N2O2S/c1-21-12-4-6-16-14(10-12)18(23-9-3-8-19)15-11-13(22-2)5-7-17(15)20-16/h4-7,10-11H,3,8-9,19H2,1-2H3
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| Chemical Name |
3-(2,7-dimethoxyacridin-9-yl)sulfanylpropan-1-amine
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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 : ~25 mg/mL (~76.12 mM)
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| 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 | 3.0448 mL | 15.2239 mL | 30.4479 mL | |
| 5 mM | 0.6090 mL | 3.0448 mL | 6.0896 mL | |
| 10 mM | 0.3045 mL | 1.5224 mL | 3.0448 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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