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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
Doublecortin-like kinase 1 (DCLK1) and DCLK2. DCLK1-IN-1 is a selective inhibitor that binds to DCLK1 and DCLK2 with IC50 values of 9.5 nM and 31 nM, respectively, in binding assays. DCLK1 is a serine/threonine kinase implicated in tumor initiation, stem cell maintenance, and neurogenesis. The compound binds to DCLK1 long isoforms but does not prevent DCLK1's microtubule-associated protein (MAP) function, suggesting that it selectively inhibits the kinase activity without disrupting the protein's structural role. DCLK2 is a closely related kinase with overlapping functions. The compound's selectivity for DCLK1 and DCLK2 over other kinases makes it a valuable tool for dissecting DCLK1 biological functions.
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| ln Vitro |
For ERK5, ACK, and LRRK2, DCLK1-IN-1 did not exhibit any discernible activity. HCT116 cells exhibit excellent binding of DCLK1-IN-1 (IC50=279 nM) to DCLK1. The DCLK1-IN-1 compound strongly inhibits DCLK1 and weakly inhibits ERK5 in the mitochondria of PATU-8988T cells and live cells [1].
DCLK1-IN-1 demonstrates potent in vitro activity against DCLK1 and DCLK2. In KINOMEscan binding assays, the compound shows IC50 values of 9.5 nM for DCLK1 and 31 nM for DCLK2. In ATP kinase assays, IC50 values are 57 nM for DCLK1 and 103 nM for DCLK2. The compound's selectivity for DCLK1 and DCLK2 over other kinases has been confirmed in broad kinase panel screening. In cell-based assays, DCLK1-IN-1 inhibits DCLK1-mediated signaling and cellular functions. The compound has low toxicity in cell-based studies, supporting its use as a chemical probe. Further detailed cell-based data are available in the primary literature. |
| ln Vivo |
Inside the mold, DCLK1-IN-1 has favorable pharmacokinetic properties, including an 81% epidermal bioavailability, an area under contour of 5506 h/ng mL, and a half-life of 2.09 hours [1].
In vivo activity of DCLK1-IN-1 has been demonstrated in preclinical models. The compound is characterized as an in vivo-compatible chemical probe, indicating that it has suitable pharmacokinetic properties for use in animal studies. DCLK1-IN-1 enables researchers to explore the role of DCLK1 in tumor initiation, stem cell biology, and other biological processes in vivo. The compound's low toxicity profile supports its use in in vivo studies. However, specific in vivo efficacy data, including animal models and dosing regimens, are not extensively detailed in the available literature summary. Further information would be available in the primary research publications. |
| Enzyme Assay |
Binding assays for DCLK1-IN-1 are performed using KINOMEscan technology, a competitive binding assay that measures the affinity of compounds for kinases. The compound is incubated with immobilized kinases, and the fraction of kinase bound is measured. IC50 values of 9.5 nM (DCLK1) and 31 nM (DCLK2) are determined. ATP kinase assays are also performed to measure the inhibition of kinase activity, with IC50 values of 57 nM (DCLK1) and 103 nM (DCLK2) determined. Selectivity against other kinases is assessed by screening the compound against a broad panel of kinases.
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| Cell Assay |
Cell-based assays for DCLK1-IN-1 are conducted using cell lines that express DCLK1 or DCLK2. Cells are treated with the compound at various concentrations, and the inhibition of DCLK1-mediated signaling and cellular functions is assessed. Endpoints may include DCLK1 kinase activity (by phosphorylation assays), cell proliferation, migration, and stem cell marker expression. The compound's low toxicity is confirmed in cell viability assays. The specificity of the observed effects can be confirmed by using cells with DCLK1 knockdown or overexpression, or by using other DCLK1 inhibitors as comparators.
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| Animal Protocol |
In vivo studies for DCLK1-IN-1 are performed in animal models of cancer and other diseases where DCLK1 plays a role. The compound is administered via various routes, and pharmacodynamic endpoints include measurement of DCLK1 activity in tissues, assessment of tumor growth or disease progression, and evaluation of toxicity. The compound's in vivo compatibility has been confirmed, supporting its use as a chemical probe in animal studies. However, specific in vivo data, including animal models, dosing, and efficacy results, are not extensively detailed in the available literature summary.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of DCLK1-IN-1 have been characterized to support its use as an in vivo-compatible chemical probe. The compound has suitable pharmacokinetic properties for use in animal studies, including adequate bioavailability and half-life. The compound's molecular weight is 527.54 and its molecular formula is C26H28F3N7O2. Storage recommendations include appropriate temperature control to maintain stability. The compound is soluble in DMSO and other organic solvents for in vitro and in vivo formulation.
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| Toxicity/Toxicokinetics |
DCLK1-IN-1 has low toxicity, supporting its use in cell-based and in vivo studies. Comprehensive toxicological data are not extensively detailed in the available literature summary, but the compound is characterized as having a favorable safety profile for a research probe. Standard laboratory safety precautions should be followed when handling the compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety glasses) and proper ventilation.
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| References | |
| Additional Infomation |
DCLK1-IN-1 is a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain. It is the first potent, selective inhibitor of DCLK1 and DCLK2, with IC50 values of 9.5 nM and 31 nM, respectively. The compound is a valuable pharmacological tool for oncology, stem cell biology, and drug discovery studies. It is not approved for clinical use and is supplied for research purposes only. The compound is available from multiple chemical suppliers.
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| Molecular Formula |
C26H28F3N7O2
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| Molecular Weight |
527.541435241699
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| Exact Mass |
527.225
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| CAS # |
2222635-15-4
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| PubChem CID |
134457640
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
38
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| Complexity |
812
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(CN1C(C2C=CC=CC=2N(C)C2=C1C=NC(=N2)NC1C=CC(=CC=1OC)N1CCN(C)CC1)=O)(F)F
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| InChi Key |
OQFCHSFVWSLDAO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H28F3N7O2/c1-33-10-12-35(13-11-33)17-8-9-19(22(14-17)38-3)31-25-30-15-21-23(32-25)34(2)20-7-5-4-6-18(20)24(37)36(21)16-26(27,28)29/h4-9,14-15H,10-13,16H2,1-3H3,(H,30,31,32)
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| Chemical Name |
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-11-methyl-5-(2,2,2-trifluoroethyl)pyrimido[4,5-b][1,4]benzodiazepin-6-one
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| Synonyms |
DCLK1IN1 DCLK1 IN 1
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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 : ~35.71 mg/mL (~67.69 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.94 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 (3.94 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 20.8 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 | 1.8956 mL | 9.4780 mL | 18.9559 mL | |
| 5 mM | 0.3791 mL | 1.8956 mL | 3.7912 mL | |
| 10 mM | 0.1896 mL | 0.9478 mL | 1.8956 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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