Synonym
MSC2530818; MSC-2530818; MSC 2530818.
IUPAC/Chemical Name
[(2S)-2-(4-Chlorophenyl)pyrrolidin-1-yl]-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methanone
InChi Key
ODRITQGYYWHQGM-INIZCTEOSA-N
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
SMILES Code
O=C(N1[C@H](C2=CC=C(Cl)C=C2)CCC1)C3=CN=C(NN=C4C)C4=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
MSC2530818 is a potent, selective and orally available CDK8 inhibitor with an IC50 of 2.6 nM for CDK8.
In vitro activity:
In a commercially available reporter displacement assay, compound 25 (MSC2530818) binds to CDK8 and CDK19 with similar affinity (4 nM), as this study has previously observed across multiple chemotypes. Furthermore, compound 25 demonstrated potent inhibition of WNT-dependent transcription in human cancer cell lines that have constitutively activated WNT signaling. For example, 25 inhibited the reporter-based luciferase readout in several cell lines bearing activating WNT-pathway mutations; LS174T (β-catenin mutant, IC50 = 32 ± 7 nM), COLO205 (APC mutant, IC50 = 9 ± 1 nM) and demonstrated inhibition of WNT3a ligand-dependent reporter readout in PA-1 cells (IC50 = 52 ± 30 nM).
Reference: J Med Chem. 2016 Oct 27;59(20):9337-9349. https://pubmed.ncbi.nlm.nih.gov/27490956/
In vivo activity:
Compound 25 (MSC2530818) was then assessed in vivo in an established SW620 human colorectal cancer xenograft model in female NCr athymic mice. Tumor-bearing mice were treated orally with compound 25 (50 mg/kg bid or 100 mg/kg qd) for 16 days. Both schedules gave a similar reduction in tumor growth (Figure 6A) with T/C ratios (based on final tumor weights) of 49% and 57%, respectively.
Reference: J Med Chem. 2016 Oct 27;59(20):9337-9349. https://pubmed.ncbi.nlm.nih.gov/27490956/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
88.03 |
| DMF:PBS (pH 7.2) (1:1) |
0.5 |
1.47 |
| DMSO |
64.3 |
188.77 |
| Ethanol |
39.0 |
114.43 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
340.81
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. doi: 10.1021/acs.jmedchem.6b00597. Epub 2016 Oct 7. PMID: 27490956.
In vitro protocol:
Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. doi: 10.1021/acs.jmedchem.6b00597. Epub 2016 Oct 7. PMID: 27490956.
In vivo protocol:
Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. doi: 10.1021/acs.jmedchem.6b00597. Epub 2016 Oct 7. PMID: 27490956.
1: Czodrowski P, Mallinger A, Wienke D, Esdar C, Poeschke O, Busch M, Rohdich F,
Eccles SA, Ortiz Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D,
Dale TC, Urbahns K, Blagg J, Schiemann K. Structure-based optimization of potent,
selective and orally bioavailable CDK8 inhibitors discovered by high throughput
screening. J Med Chem. 2016 Aug 4. [Epub ahead of print] PubMed PMID: 27490956.
