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Chemical Structure| 1489389-18-5 Chemical Structure| 1489389-18-5

Structure of CCT245737
CAS No.: 1489389-18-5

Chemical Structure| 1489389-18-5

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CCT245737 is a potent, ATP-competitive CHK1 inhibitor with an IC50 of 30-220 nM.

Synonyms: SRA737; PNT-737

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Product Details of CCT245737

CAS No. :1489389-18-5
Formula : C16H16F3N7O
M.W : 379.34
SMILES Code : N#CC1=NC=C(NC2=NC=C(C(F)(F)F)C(NC[C@H]3CNCCO3)=C2)N=C1
Synonyms :
SRA737; PNT-737
MDL No. :MFCD30489721
InChI Key :YBYYWUUUGCNAHQ-LLVKDONJSA-N
Pubchem ID :72165232

Safety of CCT245737

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Chk1

    Chk1, IC50:1.4 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
H1694 and H847 cells 1μM 72 hours To evaluate the activation of the STING pathway by SRA737, showing time-dependent activation. J Thorac Oncol. 2019 Dec;14(12):2152-2163.
H69 and H446 cells 1μM 24 hours To assess SRA737-induced micronuclei formation, showing a significant increase in MN frequency. J Thorac Oncol. 2019 Dec;14(12):2152-2163.
SCLC cell lines 10μM 96 hours To evaluate the antiproliferative activity of SRA737 on SCLC cell lines, showing a range of sensitivities to SRA737. J Thorac Oncol. 2019 Dec;14(12):2152-2163.
SW620 colorectal cancer cells 0.8 μM 84 hours Evaluate the sensitivity of SW620 cells to the CHK1 inhibitor SRA737, showing that knockdown of POLA1 and POLE2 significantly increased cell sensitivity to SRA737. Cancer Res. 2020 Apr 15;80(8):1735-1747.
A549 non-small cell lung cancer cells 0.4 μM 84 hours Evaluate the sensitivity of A549 cells to the CHK1 inhibitor SRA737, showing that knockdown of POLA1, POLE, and POLE2 significantly increased cell sensitivity to SRA737. Cancer Res. 2020 Apr 15;80(8):1735-1747.
SW620 3 μM 6 h Evaluate the effect of CCT245737 in resistant cells. Results showed that CCT245737 at 3 μM concentration inhibited 50% of pS296-CHK1. ACS Pharmacol Transl Sci. 2021 Feb 12;4(2):730-743.
AsPC-1 1 μM 6 h Evaluate the inhibitory effect of CCT245737 on CHK1. Results showed that CCT245737 at 1 μM concentration inhibited 50% of pS296-CHK1. ACS Pharmacol Transl Sci. 2021 Feb 12;4(2):730-743.
MDA-MB-231 cells 0.1-1 μg/mL 12 hours Evaluate cytotoxicity of SRA737 and DOX, results showed SRA737 significantly enhanced DOX cytotoxicity Int J Mol Sci. 2022 Jul 20;23(14):7981.
PEO1-PR cells 0.2 μM 24 hours To evaluate the effect of SRA737 on PARPi-resistant cells, results showed that SRA737 increased the expression of p-CHK1 (S345) iScience. 2024 May 15;27(7):109978.
OVCAR3 cells 0.2 μM 24 hours To evaluate the effect of SRA737 on replication stress and DNA double-strand breaks, results showed that SRA737 increased the expression of p-CHK1 (S345) and γ-H2AX iScience. 2024 May 15;27(7):109978.
OVCAR3 cells 100 nM 12 days To assess the activity of SRA737 monotherapy in CCNE1 amplified HGSOC, results showed that 100 nM SRA737 inhibited more than 50% of colony area iScience. 2024 May 15;27(7):109978.
Mammary carcinoma cells (SUM149) 0.25 μM 24 hours Evaluate the cytotoxic effects of SRA737 in combination with niraparib, showing that the combination led to cell death. Cancer Biol Ther. 2018;19(9):786-796.
Ovarian cancer cells (Spiky) 0.25 μM 24 hours Evaluate the cytotoxic effects of SRA737 in combination with niraparib, showing that the combination led to cell death. Cancer Biol Ther. 2018;19(9):786-796.
Mammary carcinoma cells (BT474) 0.25 μM 24 hours Evaluate the cytotoxic effects of SRA737 in combination with niraparib, showing that the combination led to cell death. Cancer Biol Ther. 2018;19(9):786-796.
MDA-MB-436 1819 nM (SRA737) and 546 nM (adavosertib) 24 hours Assessed cell cycle distribution, replication stress, apoptosis, and DNA double-strand breaks. Results showed a significant increase in S-phase cells (66.5% vs 23.7%) and elevated levels of p-CHK1Ser345, c-PARP, and γH2AX compared to control. BJC Rep. 2024 Apr 3;2(1):27.
OVCAR3 730 nM (SRA737) and 182 nM (adavosertib) 24 hours Assessed cell cycle distribution, replication stress, apoptosis, and DNA double-strand breaks. Results showed a significant increase in S-phase cells (50.5% vs 21%) and elevated levels of p-CHK1Ser345, c-PARP, and γH2AX compared to control. BJC Rep. 2024 Apr 3;2(1):27.
K562 cells 500 nM 24 hours CCT245737 significantly inhibited CHK1 autophosphorylation at Ser296, promoted the accumulation of DNA damage, and enhanced the cytotoxicity of VP16 in K562 cells Oncol Rep. 2020 Nov;44(5):2152-2164.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
B6129F1 mice RPP xenograft model Oral 100mg/kg 5 days on/2 days off To evaluate the antitumor activity of SRA737 alone or in combination with anti-PD-L1, showing significant tumor growth inhibition with the combination. J Thorac Oncol. 2019 Dec;14(12):2152-2163.
Mice TRAMP mouse model Oral 60 mg/kg (AZD1775), 100 mg/kg (SRA737) 5 days-on / 2 days-off for four weeks AZD1775 or SRA737 alone not only completely blocked tumor growth but also resulted in tumor regression Oncogene. 2024 Mar;43(11):789-803.
Mice Subcutaneous OVCAR3 tumor model Oral 25, 50, 100 or 150 mg/kg Once daily for 5 days, 2 days off, for 3 cycles To evaluate the anti-tumor efficacy of SRA737 monotherapy in CCNE1 amplified tumors, results showed significant tumor growth inhibition in the 100 and 150 mg/kg dose groups iScience. 2024 May 15;27(7):109978.
Athymic mice BT474 mammary tumor model Oral 25 mg/kg Once daily for 5 days Evaluate the anti-tumor effects of SRA737 in combination with niraparib, showing that the combination significantly suppressed tumor growth. Cancer Biol Ther. 2018;19(9):786-796.
NSG mice OVCAR3 and MDA-MB436 xenograft models Oral 120 mg/kg QD 2 consecutive days/7 ×3 weeks Evaluated the tumor growth inhibitory effects of the combination. Results showed significant tumor regression in the OVCAR3 model (p<0.0001) with TGI of 107.9%, and significant reduction in tumor volume in the MDA-MB-436 model (p=0.0025) with TGI of 44.7%. BJC Rep. 2024 Apr 3;2(1):27.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02797964 Advanced Solid Tumors or Non-H... More >>odgkin's Lymphoma (NHL) Less << PHASE1|PHASE2 COMPLETED 2019-10-28 Royal Marsden Hospital, Sutton... More >>, London, SM2 5PT, United Kingdom|Belfast City Hospital, Belfast, Northern Ireland, BT9 7AB, United Kingdom|Oxford University Hospitals, Headington, Oxford, OX3 7LE, United Kingdom|Velindre Cancer Centre - Cardiff, Cardiff, Whitchurch, CF14 2TL, United Kingdom|The Clatterbridge Cancer Centre, Bebington, Wirral, CH63 4JY, United Kingdom|Western General Hospital, Edinburgh, EH4 2XU, United Kingdom|The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, United Kingdom|The Leeds Teaching Hospitals of St James University Hospital, Leeds, LS9 7TF, United Kingdom|University Hospitals of Leicester, Leicester, LE1 5WW, United Kingdom|Guy's and St. Thomas, London, SE1 9RT, United Kingdom|Sarah Cannon Research Institute, London, W1G 6AD, United Kingdom|University College London Hospitals, London, W1T 7HA, United Kingdom|The Christie, Manchester, M20 4BX, United Kingdom|Freeman Hospital, Newcastle upon Tyne, NE7 7DN, United Kingdom|Sheffield Teaching Hospitals, Sheffield, S10 2SJ, United Kingdom Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.64mL

0.53mL

0.26mL

13.18mL

2.64mL

1.32mL

26.36mL

5.27mL

2.64mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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