Synonym
CCT245737; CCT 245737; CCT-245737; SRA737; SRA-737; SRA 737;
IUPAC/Chemical Name
(R)‑5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile
InChi Key
YBYYWUUUGCNAHQ-LLVKDONJSA-N
InChi Code
InChI=1S/C16H16F3N7O/c17-16(18,19)12-8-25-14(26-15-9-22-10(4-20)5-24-15)3-13(12)23-7-11-6-21-1-2-27-11/h3,5,8-9,11,21H,1-2,6-7H2,(H2,23,24,25,26)/t11-/m1/s1
SMILES Code
N#CC1=NC=C(NC2=NC=C(C(F)(F)F)C(NC[C@H]3CNCCO3)=C2)N=C1
Appearance
White to off-white solid powder
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, not in water
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
More Info
Related CAS#
1489389-23-2 (S-isomer)
1489389-18-5 (R-isomer)
Biological target:
CCT245737 is a Chk1 inhibitor, with an IC50 of 1.3 nM.
In vitro activity:
CCT245737 was a potent inhibitor of recombinant human CHK1 with IC50 of 1.4±0.3nM (mean±SD, n = 3, EZ Reader II assay). There was > 1,000-fold selectivity for CHK1 versus the functionally important kinases CDK1 and CHK2 (IC50 1.26-2.44 and 9.03 μM, respectively), and at least a 90-fold selectivity against cross-reacting kinases such as ERK8, PKD1, RSK1 and 2 (see Supplementary Table 2, 33P radiometric assay); thus demonstrating that CCT245737 is a potent and selective CHK1 inhibitor.
Reference: Oncotarget. 2016 Jan 19;7(3):2329-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823038/
In vivo activity:
Figure 5A clearly shows that 9 days oral administration of 150mg/kg CCT245737 significantly reduced the weight of the inguinal, brachial/axillary and mesenteric lymph nodes compared with vehicle treated control animals (P < 0.05). Moreover there were minimal effects on normal tissues such as the lung (Figure 5B, p = 0.904) and bone marrow (Figure 5C, p = 0.0838) or kidney (p = 0.959, not shown). There was a significant decrease in thymus weight following CCT245737 treatment (p < 0.01) suggesting some tumor involvement and spleen weight was increased significantly (p < 0.01) suggesting some splenomegaly (not shown). The treatment was well tolerated as evidenced by stable body weights (Figure 5D) and negligible effects on other parameters such as water consumption and body temperature (data not shown). Consequently these results show that CCT245737 has significant antitumor activity as an oral single-agent in a Myc-driven mouse model of B-cell lymphoma.
Reference: Oncotarget. 2016 Jan 19;7(3):2329-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823038/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
53.5 |
141.03 |
| Ethanol |
9.0 |
23.72 |
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
379.35
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:
1. Walton MI, Eve PD, Hayes A, Henley AT, Valenti MR, De Haven Brandon AK, Box G, Boxall KJ, Tall M, Swales K, Matthews TP, McHardy T, Lainchbury M, Osborne J, Hunter JE, Perkins ND, Aherne GW, Reader JC, Raynaud FI, Eccles SA, Collins I, Garrett MD. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. Oncotarget. 2016 Jan 19;7(3):2329-42. doi: 10.18632/oncotarget.4919. PMID: 26295308; PMCID: PMC4823038.
In vitro protocol:
1. Walton MI, Eve PD, Hayes A, Henley AT, Valenti MR, De Haven Brandon AK, Box G, Boxall KJ, Tall M, Swales K, Matthews TP, McHardy T, Lainchbury M, Osborne J, Hunter JE, Perkins ND, Aherne GW, Reader JC, Raynaud FI, Eccles SA, Collins I, Garrett MD. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. Oncotarget. 2016 Jan 19;7(3):2329-42. doi: 10.18632/oncotarget.4919. PMID: 26295308; PMCID: PMC4823038.
In vivo protocol:
1. Walton MI, Eve PD, Hayes A, Henley AT, Valenti MR, De Haven Brandon AK, Box G, Boxall KJ, Tall M, Swales K, Matthews TP, McHardy T, Lainchbury M, Osborne J, Hunter JE, Perkins ND, Aherne GW, Reader JC, Raynaud FI, Eccles SA, Collins I, Garrett MD. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. Oncotarget. 2016 Jan 19;7(3):2329-42. doi: 10.18632/oncotarget.4919. PMID: 26295308; PMCID: PMC4823038.
Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737)
James D. Osborne, Thomas P. Matthews, Tatiana McHardy, Nicolas Proisy, Kwai-Ming J. Cheung, Michael Lainchbury, Nathan Brown, Michael I. Walton, Paul D. Eve, Katherine J. Boxall, Angela Hayes, Alan T. Henley, Melanie R. Valenti, Alexis K. De Haven Brandon, Gary Box, Yann Jamin, Simon P. Robinson, Isaac M. Westwood, Rob L. M. van Montfort, Philip M. Leonard, Marieke B. A. C. Lamers, John C. Reader, G. Wynne Aherne, Florence I. Raynaud, Suzanne A. Eccles, Michelle D. Garrett, and Ian Collins
Publication Date (Web): May 11, 2016 (Article)
DOI: 10.1021/acs.jmedchem.5b01938
