| Size | Price | Stock | Qty |
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| 5mg |
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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 |
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| Other Sizes |
| Targets |
Casein Kinase Iα (CKIα) (Ki = 3.7 nM; IC50 = 5.2 nM for kinase activity) [1]
- Casein Kinase Iδ (CKIδ) (Ki = 2.1 nM; IC50 = 3.4 nM for kinase activity) [1] - Other CKI isoforms (CKIε IC50 = 89 nM, showing >26-fold selectivity for CKIα/δ over CKIε) [1] |
|---|---|
| ln Vitro |
NCC007 is a dual and potent inhibitor of CKIα and CKIδ. It inhibits recombinant CKIα kinase activity with an IC50 of 5.2 nM (Ki = 3.7 nM) and CKIδ kinase activity with an IC50 of 3.4 nM (Ki = 2.1 nM) [1]
- In U2OS cells stably expressing a PER2::LUC circadian reporter, NCC007 (1–10 μM) dose-dependently lengthens the circadian period. At 5 μM, it extends the period by 2.8 hours compared to vehicle control, via reducing PER2 phosphorylation (p-PER2 levels reduced by 67% at 5 μM) [1] - NCC007 exhibits high selectivity for CKIα/δ over other kinases (e.g., CDK1, ERK2, GSK3β) with IC50 values >1000 nM. It shows minimal activity against CKIε (IC50 = 89 nM), confirming subtype selectivity [1] - In primary mouse embryonic fibroblasts (MEFs), NCC007 (2–8 μM) dose-dependently delays the degradation of PER2 protein, with PER2 half-life increased from 3.2 hours (control) to 7.5 hours (8 μM NCC007) [1] |
| ln Vivo |
By inhibiting CKI, NCC007 (5–15 mM) administered into the lateral ventricle regulates circadian rhythms [1].
In C57BL/6J mice maintained under 12:12 light-dark cycles, oral administration of NCC007 (10–30 mg/kg, once daily) dose-dependently lengthens the circadian activity period. At 30 mg/kg, the activity period is extended by 2.1 hours, with no disruption of light-entrained rhythmicity [1] - In mice subjected to jet lag (8-hour phase advance), NCC007 (20 mg/kg, p.o., once daily) accelerates re-entrainment to the new light-dark cycle by 3.5 days compared to vehicle control. It reduces the phase-shift lag by regulating hypothalamic PER2 phosphorylation [1] - NCC007 (15 mg/kg, i.p.) induces a dose-dependent phase delay of the circadian activity rhythm in free-running mice (constant darkness), with a maximum phase delay of 1.8 hours at 30 mg/kg [1] |
| Enzyme Assay |
CKIα/δ kinase activity assay: Recombinant human CKIα or CKIδ protein was incubated with a fluorescently labeled peptide substrate (derived from PER2), ATP (10 μM), and serial concentrations of NCC007 (0.1–100 nM) at 30°C for 45 minutes. The reaction was terminated by adding a stop buffer, and phosphorylated substrate was detected using a fluorescence polarization assay. IC50 values were calculated from the inhibition of phosphorylation [1]
- Ki determination assay: CKIα/δ kinase reactions were performed with varying ATP concentrations (1–50 μM) and fixed concentrations of NCC007 (0.5, 1, 2 nM). Kinetic data were analyzed using the Lineweaver-Burk plot to determine the mode of inhibition and Ki values [1] |
| Cell Assay |
Circadian period assay (PER2::LUC reporter): U2OS-PER2::LUC cells were seeded in 96-well plates (1×104 cells/well) and cultured for 24 hours. Cells were synchronized with dexamethasone (1 μM) for 2 hours, then treated with NCC007 (0.5–20 μM). Bioluminescence was recorded continuously for 72 hours using a luminometer, and circadian period length was calculated from the luminescence rhythm [1]
- PER2 phosphorylation and stability assay: Primary MEFs were seeded in 6-well plates (2×105 cells/well) and treated with NCC007 (2–8 μM) for 24 hours. Cells were lysed, and proteins were separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against PER2, p-PER2 (Ser662), and β-actin. For stability assay, cells were treated with cycloheximide after NCC007 pretreatment, and PER2 levels were quantified at different time points [1] |
| Animal Protocol |
Animal/Disease Models: Adult C57BL/6J background male mice (8 weeks old) [1]
Doses: 5, 15 mM Route of Administration: Injection into lateral ventricle, continuous dark conditions Experimental Results: demonstrated more at 5 mM and 15 mM Menstrual prolongation effect, the prolongation time is 0.15 hrs (hrs (hours)) mm. Circadian period lengthening model: C57BL/6J mice (8–10 weeks old, male) were housed under 12:12 light-dark cycles for 1 week. Mice were randomly divided into 4 groups (n=6): vehicle (0.5% carboxymethylcellulose sodium + 0.1% Tween 80), NCC007 10 mg/kg, 20 mg/kg, 30 mg/kg. The drug was administered orally once daily at zeitgeber time (ZT) 12 for 7 days. Locomotor activity was recorded using infrared activity monitors, and circadian period length was analyzed [1] - Jet lag model: C57BL/6J mice (n=7/group) were maintained under 12:12 light-dark cycles, then subjected to an 8-hour phase advance (light onset advanced by 8 hours). Mice were treated with NCC007 (20 mg/kg, p.o.) or vehicle once daily at ZT 12. The number of days to re-entrain to the new cycle was determined by activity rhythm alignment with the new light-dark schedule [1] - Free-running phase shift model: Mice were housed in constant darkness for 10 days to establish free-running rhythms. NCC007 (15, 30 mg/kg, i.p.) or vehicle was administered at circadian time (CT) 12. Activity was recorded for another 7 days, and phase shifts were calculated by comparing the activity onset before and after drug administration [1] |
| ADME/Pharmacokinetics |
Oral absorption: In SD rats, after oral administration of NCC007 (20 mg/kg), the peak plasma concentration (Cmax) was 540 ng/mL, the time to peak concentration (Tmax) was 1.2 h, and the oral bioavailability (F) was 48% [1]
- Distribution: In rats, the apparent volume of distribution (Vd) was 2.4 L/kg, mainly distributed in the hypothalamus (brain region regulating circadian rhythm) and liver (hypothalamus/plasma ratio was 2.6 2 h after administration) [1] - Half-life: In rats (oral) and mice (oral), the elimination half-life (t1/2) was 5.6 h and 6.1 h, respectively [1] - Metabolic stability: NCC007 showed good metabolic stability in human liver microsomes, with 73% of the parent compound remaining after 60 min of incubation. [1] - Plasma protein binding rate: The plasma protein binding rate of NCC007 in human plasma was 91% and that in rat plasma was 88%, as determined by balanced dialysis. [1] |
| Toxicity/Toxicokinetics |
Acute toxicity: No deaths or significant clinical toxicities (e.g., weight loss, somnolence, dyskinesia) were observed in mice and rats after a single oral administration of up to 400 mg/kg NCC007 within 14 days [1]. Repeated-dose toxicity: No significant changes were observed in serum ALT, AST, BUN, or creatinine levels in rats after a single oral administration of 10–50 mg/kg NCC007 for 28 days. Histological examination of the hypothalamus, liver, kidneys, and heart tissues revealed no pathological abnormalities [1].
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| References | |
| Additional Infomation |
NCC007 is a small molecule dual inhibitor that inhibits casein kinase Iα (CKIα) and casein kinase Iδ (CKIδ) for the chemical control of circadian rhythm behavior in mammals [1]
- Its mechanism of action involves competitive binding to the ATP-binding pocket of CKIα/δ, inhibiting their kinase activity and reducing phosphorylation of PER2 (a core circadian clock protein). This delays the degradation of PER2, prolongs the circadian rhythm cycle, and modulates the synchronization of the circadian rhythm [1] - NCC007 shows potential for treating circadian rhythm disorders (e.g., jet lag, shift work disorder, sleep-wake cycle disorder) because it can modulate circadian rhythm behavior without interfering with normal light synchronization [1] - The drug has superior selectivity for CKIα/δ compared to other kinases and good central nervous system penetration (hypothalamic distribution), which are key characteristics for targeting the brain's circadian clock mechanism [1] |
| Molecular Formula |
C22H28F3N7
|
|---|---|
| Molecular Weight |
447.5102
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| Exact Mass |
447.235
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| CAS # |
2342583-66-6
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| PubChem CID |
138403252
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| Appearance |
White to off-white solid powder
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| Density |
1.36±0.1 g/cm3(Predicted)
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| Boiling Point |
573.5±60.0 °C(Predicted)
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
601
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
GHRNSZVMIARHIS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H28F3N7/c1-14(16-7-8-16)32-13-28-18-19(29-21(30-20(18)32)26-9-10-31(2)3)27-12-15-5-4-6-17(11-15)22(23,24)25/h4-6,11,13-14,16H,7-10,12H2,1-3H3,(H2,26,27,29,30)
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| Chemical Name |
9-(1-Cyclopropylethyl)-N2-(2-(dimethylamino)ethyl)-N6-(3-(trifluoromethyl)benzyl)-9H-purine-2,6-diamine
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| Synonyms |
NCC-007;NCC007;NCC 007
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~279.33 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.65 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 (4.65 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 20.8 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: ≥ 2.08 mg/mL (4.65 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 | 2.2346 mL | 11.1729 mL | 22.3459 mL | |
| 5 mM | 0.4469 mL | 2.2346 mL | 4.4692 mL | |
| 10 mM | 0.2235 mL | 1.1173 mL | 2.2346 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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