| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 2.52 μM (CSNK1A1 kinase)[1]
The primary target of CSNK1-IN-2 is CSNK1A1 (casein kinase 1 isoform alpha), with an IC50 of 2.52 uM. It also shows inhibitory activity against CSNK1D (IC50 = 8.48 uM) and surprisingly exhibits potent activity against wild-type EGFR kinase (IC50 = 2.74 nM). Off-target activity includes weak inhibition of CSNK1A1 under high ATP conditions (IC50 = 107 uM). |
|---|---|
| ln Vitro |
CSNK1-IN-2 (example 7) exhibits inhibitory activity with IC50 values of 2.52 μM, 8.48 μM, and 107 μM against CSNK1A1, CSNK1D, and CSNK1A1 (high ATP) [1]. Wild-type EGFR kinase is inhibited by CSNK1-IN-2, with an IC50 value of 2.74 nM[1].
In biochemical assays, CSNK1-IN-2 demonstrates potent inhibitory activity against CSNK1A1 kinase. It also shows inhibition for CSNK1D and CSNK1A1 (in high ATP). The compound exhibits significant activity against wild-type EGFR kinase, making it a multi-target inhibitor useful for exploring kinase-related pathways, particularly proliferative disorders and cancer biology. |
| ln Vivo |
Specific in vivo activity data for CSNK1-IN-2 is not publicly available. Based on its mechanism as a CK1/EGFR inhibitor, it could be tested in mouse xenograft models of EGFR-driven cancers (e.g., NSCLC) or in models of circadian rhythm disorders. Its ability to cross the blood-brain barrier and its in vivo efficacy require further experimental validation.
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| Enzyme Assay |
A non-cellular radiometric or FRET-based kinase assay is used. Recombinant CSNK1A1 kinase is incubated with a peptide substrate and gamma-33P-ATP or a labeled ATP analog. Varying concentrations of CSNK1-IN-2 (0-100 uM) are added, and the reaction proceeds for 30-60 minutes. The phosphorylated product is captured on a filter or detected by fluorescence, and IC50 values are calculated.
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| Cell Assay |
Cell viability assays are conducted using cancer cell lines that are sensitive to CK1 or EGFR inhibition, such as H1650 or H1975 lung cancer cells. Cells are seeded in 96-well plates and treated with a concentration range of CSNK1-IN-2 (0-100 uM) for 48-72 hours. Cell viability is measured using MTT or CellTiter-Glo assays, and IC50 values are calculated to assess the compound‘s anti-proliferative effect.
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| Animal Protocol |
An in vivo xenograft model could be established using H1650 cells implanted subcutaneously in nude mice. Once tumors reach approximately 150 mm3, CSNK1-IN-2 is administered orally (p.o.) or intraperitoneally (i.p.) at doses of 10-50 mg/kg daily for 14-21 days. Tumor volumes are measured with calipers twice weekly, and body weight is monitored. At study endpoint, tumors are excised and weighed for growth inhibition assessment.
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| ADME/Pharmacokinetics |
CSNK1-IN-2 has a molecular weight of 483.54 (C28H26FN5O2). Solubility data indicates it is soluble in DMSO at 10 mg/mL (20.68 mM). For in vivo studies, it can be formulated using 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline (clear solution at ≥1 mg/mL) or 10% DMSO + 90% corn oil. Standard pharmacokinetic parameters have not been fully published.
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| Toxicity/Toxicokinetics |
Specific toxicological data for CSNK1-IN-2 is not available from public sources. As an inhibitor of EGFR and CK1, potential toxicity may include gastrointestinal disturbances, skin rash (typical of EGFR inhibitors), and effects on circadian rhythms. The compound is intended for research use only and is not approved for human therapy.
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| References |
[1]. Volker Schulze, et al. 3-amino-2-[2-(acylamino)pyridin-4-yl]-1,5,6,7-tetrahydro-4h-pyrrolo[3,2-c]pyridin-4-one as csnk1 inhibitors. Patent. WO2020161257 A1.
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| Additional Infomation |
CSNK1-IN-2 is also referred to as Example 7 in patent WO2020161257 A1. Its IUPAC name is (2R)-N-[4-(3-anilino-5-methyl-4-oxo-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide. It can be used in the research of proliferative disorders. The compound remains in preclinical development and has not entered clinical trials.
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| Molecular Formula |
C28H26FN5O2
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|---|---|
| Molecular Weight |
483.536749362946
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| Exact Mass |
483.207
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| CAS # |
2468783-76-6
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| PubChem CID |
154674407
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| Appearance |
Light yellow to light brown solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
769
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C1=CC=C(C=C1)F)C(=O)NC2=NC=CC(=C2)C3=C(C4=C(N3)CCN(C4=O)C)NC5=CC=CC=C5
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| InChi Key |
UYAQWCZWVIFRCN-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C28H26FN5O2/c1-17(18-8-10-20(29)11-9-18)27(35)33-23-16-19(12-14-30-23)25-26(31-21-6-4-3-5-7-21)24-22(32-25)13-15-34(2)28(24)36/h3-12,14,16-17,31-32H,13,15H2,1-2H3,(H,30,33,35)/t17-/m1/s1
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| Chemical Name |
(2R)-N-[4-(3-anilino-5-methyl-4-oxo-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide
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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: 10 mg/mL (20.68 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.07 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0681 mL | 10.3404 mL | 20.6808 mL | |
| 5 mM | 0.4136 mL | 2.0681 mL | 4.1362 mL | |
| 10 mM | 0.2068 mL | 1.0340 mL | 2.0681 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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