CCT241533Potent Chk2 inhibitor CAS# 1262849-73-9 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1262849-73-9 | SDF | Download SDF |
| PubChem ID | 45254037 | Appearance | Powder |
| Formula | C23H27FN4O4 | M.Wt | 442.48 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO | ||
| Chemical Name | (6E)-4-fluoro-6-[4-[[(3S,4R)-4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl]amino]-6,7-dimethoxy-1H-quinazolin-2-ylidene]cyclohexa-2,4-dien-1-one | ||
| SMILES | CC(C)(C1CNCC1NC2=NC(=C3C=C(C=CC3=O)F)NC4=CC(=C(C=C42)OC)OC)O | ||
| Standard InChIKey | IXTQNANZDPZION-KFXCQKJJSA-N | ||
| Standard InChI | InChI=1S/C23H27FN4O4/c1-23(2,30)15-10-25-11-17(15)27-21-13-8-19(31-3)20(32-4)9-16(13)26-22(28-21)14-7-12(24)5-6-18(14)29/h5-9,15,17,25-26,30H,10-11H2,1-4H3,(H,27,28)/b22-14+/t15-,17-/m1/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | CCT241533 is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM.In Vitro:CCT241533 hydrochloride inhibits CHK2 with an IC50 of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2]. References: | |||||
CCT241533 Dilution Calculator
CCT241533 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.26 mL | 11.2999 mL | 22.5999 mL | 45.1998 mL | 56.4997 mL |
| 5 mM | 0.452 mL | 2.26 mL | 4.52 mL | 9.04 mL | 11.2999 mL |
| 10 mM | 0.226 mL | 1.13 mL | 2.26 mL | 4.52 mL | 5.65 mL |
| 50 mM | 0.0452 mL | 0.226 mL | 0.452 mL | 0.904 mL | 1.13 mL |
| 100 mM | 0.0226 mL | 0.113 mL | 0.226 mL | 0.452 mL | 0.565 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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CHK2 is a checkpoint kinase involved in the ATM-mediated response to double-strand DNA breaks. Inhibitors of CHK2 may increase the efficacy of genotoxic cancer therapies. CCT241533 has been identified and characterized as a novel CHK2 kinase inhibitor.
In vitro: CCT241533 inhibits CHK2 with an IC50 of 3 nmol/L and shows minimal cross-reactivity against a panel of kinases at 1 mmol/L. CCT241533 did not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines [1]. Moreover, as the most potent CHK2 inhibitor identified in the series, CCT241533 shows potent selectivity (63-fold) over CHK1 and low hERG inhibition (hERGIC50=22 μM) [2].
In silico: X-ray crystallography confirmed that CCT241533 bound to CHK2 in the ATP pocket. Overall, the binding mode was found to be very highly conserved relative to previous compounds, with all of the key hydrogen bond interactions maintained. The potency gained with CCT241533 therefore appears to be due to the presence of the two methoxy substituents occupying the solvent exposed region of the enzyme, and contributions from the isopropyl alcohol substituent, which may participate in a second intramolecular hydrogen bond to the quinazoline exocyclicNH [2].
Clinical trial: No clinical data are available.
References:
[1] Anderson VE, Walton MI, Eve PD, Boxall KJ, Antoni L, Caldwell JJ, Aherne W, Pearl LH, Oliver AW, Collins I, Garrett MD. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011;71(2):463-72.
[2] Caldwell JJ, Welsh EJ, Matijssen C, Anderson VE, Antoni L, Boxall K, Urban F, Hayes A, Raynaud FI, Rigoreau LJ, Raynham T, Aherne GW, Pearl LH, Oliver AW, Garrett MD, Collins I. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011;54(2):580-90.
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CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors.[Pubmed:21239475]
Cancer Res. 2011 Jan 15;71(2):463-72.
CHK2 is a checkpoint kinase involved in the ATM-mediated response to double-strand DNA breaks. Its potential as a drug target is still unclear, but inhibitors of CHK2 may increase the efficacy of genotoxic cancer therapies in a p53 mutant background by eliminating one of the checkpoints or DNA repair pathways contributing to cellular resistance. We report here the identification and characterization of a novel CHK2 kinase inhibitor, CCT241533. X-ray crystallography confirmed that CCT241533 bound to CHK2 in the ATP pocket. This compound inhibits CHK2 with an IC(50) of 3 nmol/L and shows minimal cross-reactivity against a panel of kinases at 1 mumol/L. CCT241533 blocked CHK2 activity in human tumor cell lines in response to DNA damage, as shown by inhibition of CHK2 autophosphorylation at S516, band shift mobility changes, and HDMX degradation. CCT241533 did not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, this compound significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal was seen with a PARP inhibitor alone, and this activation was abolished by CCT241533, implying that the potentiation of PARP inhibitor cell killing by CCT241533 was due to inhibition of CHK2. Consequently, our findings imply that CHK2 inhibitors may exert therapeutic activity in combination with PARP inhibitors.
