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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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Purity: ≥98%
MSC2530818 is novel, potent, selective and orally available small molecule inhibitor of cyclin dependent kinase CDK8 with the IC50 of 2.6 nM. It has good kinase selectivity, high biochemical and cellular potency, microsomal stability, and a respectable oral bioavailability, among other excellent pharmacokinetic and pharmacodynamic properties. After WNT signaling is activated, β-catenin-dependent transcription is regulated by the mediator complex-associated cyclin-dependent kinase CDK8. Several lines of evidence imply that CDK8 may function as an oncogene during the course of colorectal cancer development. Following a high-throughput screening campaign, MSC2530818 was discovered and advanced through structure-based design. MSC2530818 showed enough potency and selectivity to move forward with preclinical in vivo safety and efficacy investigations.
| Targets |
CDK8 (IC50 = 2.6 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Having an IC50 of 2.6 nM, MSC2530818 is a new, potent, selective, and oral small molecule inhibitor of cyclin-dependent kinase CDK8.
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| Cell Assay |
In human cancer cell lines that have constitutively activated WNT signaling, SC2530818 exhibits strong suppression of WNT-dependent transcription. For instance, MSC2530818 inhibits the reporter-based luciferase readout in a number of cell lines carrying activating mutations in the WNT pathway, such as LS174T (a β-catenin mutant with an IC50 of 32±7 nM) and COLO205 (an APC mutant with an IC50 of 9±1 nM).It also shows inhibition of the WNT3a ligand-dependent reporter readout in PA-1 cells (IC50=52±30 nM). MSC2530818 shows minimal hERG inhibition and minimal activity in the CEREP panel. It is the only compound with activity below 10 μM, with an IC50 of 8.5 μM on the dopamine transporter. Additionally, MSC2530818 does not inhibit any cytochrome P450 subtypes and is a soluble CDK8 inhibitor with high permeability and low efflux ratio in Caco-2 cells.
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| References |
| Molecular Formula |
C18H17CLN4O
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| Molecular Weight |
340.81
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| Exact Mass |
340.11
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| Elemental Analysis |
C, 63.44; H, 5.03; Cl, 10.40; N, 16.44; O, 4.69
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| CAS # |
1883423-59-3
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| Appearance |
Solid powder
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| SMILES |
CC1=C2C=C(C=NC2=NN1)C(=O)N3CCC[C@H]3C4=CC=C(C=C4)Cl
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| InChi Key |
ODRITQGYYWHQGM-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C18H17ClN4O/c1-11-15-9-13(10-20-17(15)22-21-11)18(24)23-8-2-3-16(23)12-4-6-14(19)7-5-12/h4-7,9-10,16H,2-3,8H2,1H3,(H,20,21,22)/t16-/m0/s1
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| Chemical Name |
[(2S)-2-(4-chlorophenyl)pyrrolidin-1-yl]-(3-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)methanone
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (8.07 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 27.5 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: 2.75 mg/mL (8.07 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 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: ≥ 2.75 mg/mL (8.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9342 mL | 14.6709 mL | 29.3419 mL | |
| 5 mM | 0.5868 mL | 2.9342 mL | 5.8684 mL | |
| 10 mM | 0.2934 mL | 1.4671 mL | 2.9342 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.
Figure 1. (A) Crystal structure of CDK8/cyclin C complexed with compound6(blue).J Med Chem.2016 Oct 27;59(20):9337-9349. |
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Figure 5. (A) Crystal structure of25(violet) complexed with CDK8-cyclin C. (B) Superposition of the25(violet) and6(blue) crystal structures.
Efficacy study of compound25(MSC2530818) in SW620 human colorectal cancer xenografts.J Med Chem.2016 Oct 27;59(20):9337-9349. |
 Figure 2. (A) SZMAP and WaterMap calculations have been performed for the crystal structure of compound6complexed to CDK8/cyclin C.J Med Chem.2016 Oct 27;59(20):9337-9349. |
Figure 3. (A) Selectivity grids for the CDK8-specific regions of the active site.J Med Chem.2016 Oct 27;59(20):9337-9349. |
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 Figure 4. (A) Crystal structure of17(orange) in complex CDK8/cyclin C.J Med Chem.2016 Oct 27;59(20):9337-9349. |
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