WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206604
CAS#: 1489389-18-5
Description: CCT245737, also known as SRA737, is a potent, selective and orally active checkpoint kinase 1 (CHK1) inhibitor. CCT245737 showed CHK1 IC50 = 1.3 nM, CHK2 IC50 = 2440 nM, G2 check point abrogation IC50 = 30 nM. Mouse F (oral)=100%. CCT245737 demonstrated a favorable physicochemical, PK, and PD-efficacy profile. The serine-threonine kinase CHK1 is a critical component of the cellular response to DNA damage, especially the repair of DNA breaks arising during replication or caused by DNA damaging chemotherapies and ionizing radiation.
Hodoodo Cat#: H206604
Name: CCT245737
CAS#: 1489389-18-5
Chemical Formula: C16H16F3N7O
Exact Mass: 379.14
Molecular Weight: 379.347
Elemental Analysis: C, 50.66; H, 4.25; F, 15.02; N, 25.85; O, 4.22
Related CAS #: 1489389-18-5
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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 53.5 | 141.03 | |
| Ethanol | 9.0 | 23.72 |
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
