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| Targets |
CRT0066854 targets the atypical PKC isoforms PKCι and PKCζ, with IC50 values of 132 nM and 639 nM, respectively. It also inhibits the Rho-associated kinase II (ROCK2) kinase domain with an IC50 of 620 nM. The compound is selective for these atypical PKCs and ROCK2 over typical PKCs and 98 other kinases in a panel at 1 µM. It functions by decreasing the phosphorylation of the atypical PKC substrate lethal giant larvae 2 (LLGL2).
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| ln Vitro |
CRT0066854 substitutes a key Asn-Phe-Asp motif that is part of the adenosine-binding pocket and binds to the acidic patch used by arginine-rich PKC substrates [1]. CRT0066854 (0.2-1.2 μM; 6 days) was able to restore polarized morphogenesis of dysplastic H-Ras spheroids, and the greatest proportion of spheroids with PSAL was at the lower dose of 1.2 μM [1].
In vitro, CRT0066854 decreases the viability of A549 lung carcinoma cells with an IC50 of 3.47 µM. It also decreases colony formation in HeLa cells by 65% when used at a concentration of 1 µM. In functional assays, the compound impairs lumen formation in MDCK cells in a Matrigel assay and inhibits the migration of NRK-49F cells in a wound-healing assay. It also decreases phosphorylation of the aPKC substrate LLGL2 in HEK293 cells expressing PKCι and LLGL2. |
| ln Vivo |
No specific in vivo activity data is publicly available for CRT0066854 HCl. As a research compound, its in vivo efficacy and pharmacokinetic properties have not been extensively reported in the available literature. Further studies would be needed to establish its in vivo activity, particularly in cancer models where aPKC inhibition is being investigated as a therapeutic strategy.
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| Enzyme Assay |
In cell-free enzymatic assays, CRT0066854's activity is evaluated by measuring its inhibition of PKCι, PKCζ, or ROCK2 kinase activity. The kinase of interest is incubated with a substrate peptide and ATP in the presence of varying concentrations of the inhibitor. The phosphorylation of the substrate is measured using techniques such as radioactivity (e.g., 32P-ATP incorporation) or fluorescence-based methods. The IC50 value is calculated from the concentration-response curve.
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| Cell Assay |
In vitro cell-based experiments with CRT0066854 typically involve culturing cancer cell lines such as A549 (lung carcinoma) or HeLa (cervical carcinoma). Cells are treated with various concentrations of the compound for 48-72 hours, and cell viability is assessed using standard assays such as MTT or CellTiter-Glo. Colony formation assays are performed to evaluate the long-term anti-proliferative effects. Migration and invasion assays (e.g., wound healing or Boyden chamber assays) are used to study the compound's effect on cell motility.
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| Animal Protocol |
No specific in vivo animal protocols are publicly available for CRT0066854 HCl. The compound is a research tool primarily characterized in vitro. If in vivo studies were to be conducted, typical protocols would involve tumor xenograft models in immunodeficient mice, where the compound would be administered orally or intraperitoneally, and tumor growth would be monitored.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for CRT0066854 HCl. As a research compound, its absorption, distribution, metabolism, and excretion (ADME) properties have not been extensively characterized. The compound is cell-permeable and is typically dissolved in DMSO for in vitro experiments. For in vivo use, it may be formulated in appropriate vehicles.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for CRT0066854 HCl. In cell-based assays, the compound shows anti-proliferative effects at micromolar concentrations, indicating potential cytotoxicity in sensitive cell lines. The compound is for research use only and is not intended for human therapeutic applications. No systemic toxicity studies have been reported.
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| References | |
| Additional Infomation |
CRT0066854 HCl is a potent and selective inhibitor of atypical PKC isoforms and ROCK2. Its molecular formula is C24H25N5S·HCl and its molecular weight is 415.6 (free base). The compound is also known as (2S)-3-phenyl-N1-[2-(pyridin-4-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl]propane-1,2-diamine. It is a valuable research tool for studying aPKC signaling in cancer and cell biology. It is not approved for clinical use and is available for research purposes only.
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| Molecular Formula |
C24H25N5S
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| Molecular Weight |
415.5538
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| Exact Mass |
415.183
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| CAS # |
1438881-19-6
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| Related CAS # |
CRT0066854 hydrochloride;2250019-91-9
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| PubChem CID |
70702288
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| Appearance |
White to yellow solid powder
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| LogP |
5.387
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
536
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CCC2=C(C1)C3=C(N=C(N=C3S2)C4=CC=NC=C4)NC[C@H](CC5=CC=CC=C5)N
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| InChi Key |
NRHASZRDWOUMFD-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C24H25N5S/c25-18(14-16-6-2-1-3-7-16)15-27-23-21-19-8-4-5-9-20(19)30-24(21)29-22(28-23)17-10-12-26-13-11-17/h1-3,6-7,10-13,18H,4-5,8-9,14-15,25H2,(H,27,28,29)/t18-/m0/s1
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| Chemical Name |
(2S)-3-phenyl-1-N-(2-pyridin-4-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl)propane-1,2-diamine
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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 (~120.32 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 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 25.0 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: ≥ 2.5 mg/mL (6.02 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 | 2.4064 mL | 12.0322 mL | 24.0645 mL | |
| 5 mM | 0.4813 mL | 2.4064 mL | 4.8129 mL | |
| 10 mM | 0.2406 mL | 1.2032 mL | 2.4064 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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