| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
| Targets |
CRT0066854 targets atypical protein kinase C (PKC) isoforms PKCι and PKCζ, as well as ROCK-II. PKCι and PKCζ are involved in cell polarity, proliferation, and survival. By inhibiting these kinases, CRT0066854 modulates cell signaling pathways. It inhibits lethal giant larvae 2 (LLGL2) phosphorylation and restores polarized morphogenesis.
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|---|---|
| ln Vitro |
The essential Asn-Phe-Asp motif in the adenosine-binding pocket is replaced by CRT0066854 hydrochloride, which also interacts with the acidic patch that arginine-rich PKC substrates use [1]. Stemmed H-Ras spheroids were able to have their polarized morphogenesis restored by CRT0066854 hydrochloride (0.2-1.2 μM; 6 days), with the lowest dose of 1.2 μM containing the highest percentage of spheroids with PSAL [1].
CRT0066854 exhibits potent in vitro activity as a PKC inhibitor. It inhibits PKCι with an IC50 of 132 nM, PKCζ with an IC50 of 639 nM, and ROCK-II with an IC50 of 620 nM. It restores polarized morphogenesis in oncogene-expressing MDCK cells and decreases colony formation in HeLa cells. These in vitro activities confirm its potential as a research tool for studying PKC signaling. |
| ln Vivo |
In vivo, CRT0066854 has been studied for its effects on PKC signaling and tumor growth. Its ability to inhibit PKCι and PKCζ may have implications for cancer therapy. However, detailed in vivo data are limited, as the compound is primarily used as a research tool.
|
| Enzyme Assay |
In vitro kinase assays for CRT0066854 involve measuring its inhibition of PKCι, PKCζ, and ROCK-II kinase activity. These assays use recombinant kinases and peptide substrates. The enzyme is incubated with the substrate and ATP in the presence of varying concentrations of CRT0066854. The phosphorylation of the substrate is measured to determine the IC50 values (132 nM for PKCι, 639 nM for PKCζ, 620 nM for ROCK-II).
|
| Cell Assay |
In vitro cellular assays for CRT0066854 are conducted in MDCK cells, HeLa cells, and other cancer cell lines. Cells are treated with the compound at various concentrations, and cell polarity is assessed by measuring morphogenesis. Colony formation is assessed in HeLa cells. Cell proliferation, migration, and invasion are measured using standard assays. LLGL2 phosphorylation is measured by Western blot.
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| Animal Protocol |
In vivo animal experiments with CRT0066854 are limited, as the compound is primarily used as a research tool. Its effects on tumor growth and PKC signaling could be studied in mouse xenograft models of cancer. However, detailed protocols are not extensively published.
|
| ADME/Pharmacokinetics |
CRT0066854 hydrochloride has a molecular weight of approximately 480 g/mol. The compound is soluble in DMSO and is typically stored at -20°C. Its half-life and bioavailability have not been extensively characterized.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicological data for CRT0066854 are limited. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. Further toxicity studies would be required to support any potential clinical development.
|
| References | |
| Additional Infomation |
CRT0066854 hydrochloride is a potent and selective inhibitor of atypical PKC isoforms PKCι and PKCζ. It inhibits PKCι, PKCζ, and ROCK-II with IC50 values of 132 nM, 639 nM, and 620 nM, respectively. It restores polarized morphogenesis and decreases colony formation. It is used in research to study PKC signaling.
|
| Molecular Formula |
C24H27CL2N5S
|
|---|---|
| Molecular Weight |
488.47568154335
|
| Exact Mass |
487.136
|
| CAS # |
2250019-91-9
|
| Related CAS # |
CRT0066854;1438881-19-6
|
| PubChem CID |
131954580
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
536
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
Cl.Cl.S1C2C(=C(N=C(C3C=CN=CC=3)N=2)NC[C@H](CC2C=CC=CC=2)N)C2=C1CCCC2
|
| InChi Key |
NYUVOWXZRBZQBA-NTEVMMBTSA-N
|
| InChi Code |
InChI=1S/C24H25N5S.2ClH/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);2*1H/t18-;;/m0../s1
|
| 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;dihydrochloride
|
| Synonyms |
CRT-0066854 HCl; CRT 0066854 HCl
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: ~100 mg/mL (~221.2 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (11.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (50.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 5 mg/mL (11.06 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 DMSO stock solution (50.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0472 mL | 10.2358 mL | 20.4717 mL | |
| 5 mM | 0.4094 mL | 2.0472 mL | 4.0943 mL | |
| 10 mM | 0.2047 mL | 1.0236 mL | 2.0472 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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