DC Chemicals Limited
China
Product Name: CCT241533 (hydrochloride)
Price: $650.0/100mg $1300.0/250mg $2600.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

1431697-96-9

1431697-96-9 structure

1431697-96-9 structure

Name: CCT241533 hydrochloride
Chemical Name: CCT241533 hydrochloride
CAS Number: 1431697-96-9
Molecular Formula: C₂₃H₂₈ClFN₄O₄
Molecular Weight: 478.94
Catalog: Signaling Pathways Cell Cycle/DNA Damage Checkpoint Kinase (Chk)
Create Date: 2018-10-21 20:27:09
Modify Date: 2024-01-10 22:44:30
CCT241533 hydrochloride is a potent and selective CHK2 inhibitor with an IC50 of 3 nM and a Ki of 1.16 nM.

Name	CCT241533 hydrochloride
Synonyms	4-Fluoro-2-(4-{[(3S,4R)-4-(2-hydroxy-2-propanyl)-3-pyrrolidinyl]amino}-6,7-dimethoxy-2-quinazolinyl)phenol hydrochloride (1:1) 3-Pyrrolidinemethanol, 4-[[2-(5-fluoro-2-hydroxyphenyl)-6,7-dimethoxy-4-quinazolinyl]amino]-α,α-dimethyl-, (3R,4S)-, hydrochloride (1:1) MFCD23380595 CCT241533 (hydrochloride)

Description	CCT241533 hydrochloride is a potent and selective CHK2 inhibitor with an IC50 of 3 nM and a Ki of 1.16 nM.
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> Checkpoint Kinase (Chk) Research Areas >> Cancer
Target	Chk2:3 nM (IC50) Chk1:245 nM (IC50)
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].
Cell Assay	HT-29, HeLa and MCF-7 cells are exposed to a fixed concentration (GI50) of CCT241533 in combination with increasing concentrations of either PARP inhibitor or cytotoxic drug in a 96 hour SRB assay or 7-10 day colony forming assay. The ability of CCT241533 to enhance cell killing is expressed as a potentiation index (PI) which is the ratio of GI50 for the genotoxic or PARP inhibitor alone: GI50 for the genotoxic or PARP inhibitor in combination with a CHK2 inhibitor. Thus PI>1 indicates potentiation and PI<1 indicates protection[1].
References	[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72. [2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.

Molecular Formula	C₂₃H₂₈ClFN₄O₄
Molecular Weight	478.94
Storage condition	2-8℃