KU-60019

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H33N3O5S
Molecular Weight	547.665
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CN(CC(=O)NC2=CC3=C(SC4=C(C3)C=CC=C4C5=CC(=O)C=C(O5)N6CCOCC6)C=C2)C[C@@H](C)O1

InChI

InChIKey=SCELLOWTHJGVIC-BGYRXZFFSA-N

InChI=1S/C30H33N3O5S/c1-19-16-32(17-20(2)37-19)18-28(35)31-23-6-7-27-22(13-23)12-21-4-3-5-25(30(21)39-27)26-14-24(34)15-29(38-26)33-8-10-36-11-9-33/h3-7,13-15,19-20H,8-12,16-18H2,1-2H3,(H,31,35)/t19-,20+

HIDE SMILES / InChI

Molecular Formula	C30H33N3O5S
Molecular Weight	547.665
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23620409 | https://www.ncbi.nlm.nih.gov/pubmed/19808981

KU-60019 is a selective ATM kinase inhibitor. ATM is an ataxia telangiectasia (A-T) mutated, which plays a critical role in cell cycle checkpoints and DNA repair. Thus, specific small molecule inhibitors targeting ATM could perhaps be developed into efficient radiosensitizers. KU-60019 was a highly effective radiosensitizer of human glioma cells. A-T fibroblasts were not radiosensitized by KU-60019 and were suggested that the ATM kinase was specifically targeted. In xenograft models was shown, that the combination of KU-60019 and radiation significantly increased survival of mice than KU-60019 alone, radiation alone, or no treatment. In addition, p53-mutant gliomas were much more sensitive to KU-60019 radiosensitization than wild-type glioma.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine-protein kinase ATM 4 Target ID: Q13315 Gene ID: 472.0 Gene Symbol: ATM Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19808981	Inhibitor 8297		6.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Glioma 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23620409	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion.	2009 Oct	19808981
ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation.	2013 Jun 15	23620409

Patents

Sample Use Guides

In Vivo Use Guide

orthotopic xenograft mice: Mice with U1242/luc-GFP intracranial tumors were implanted with osmotic pumps loaded with KU-60019 7 days after cell implantation, followed by a single dose of radiation on day 13. Mice treated with KU-60019 and radiation survived for 109 days, significantly longer (P = 0.004 vs. all other treatments) than mice treated with KU-60019 alone (35 days), radiation alone (34 days), or after no treatment (27 days)

Route of Administration: Other

In Vitro Use Guide

KU-60019 treatment (3 μM) blocks basal and insulin-induced AKT S473 phosphorylation and completely reduces radiation-induced AKT phosphorylation below the level of control. KU-60019 at 3 μM significantly inhibits migration and invasion of human glioma U87 cells, as well as U1242 cells. The effect of KU-60019 on AKT S473 phosphorylation can be seen in glioma cell lines and normal fibroblasts but not in A-T (h-TERT) cells, and can be significantly blocked by phosphatase inhibitor okadaic acid, suggesting a critical role of ATM kinase in regulating AKT phosphorylation via unknown phosphatase.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:16:56 UTC 2023` Edited by `admin` on `Sat Dec 16 09:16:56 UTC 2023`
Record UNII	IAN358A69K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

KU-60019

Common Name

English

4-MORPHOLINEACETAMIDE, 2,6-DIMETHYL-N-(5-(6-(4-MORPHOLINYL)-4-OXO-4H-PYRAN-2-YL)-9H-THIOXANTHEN-2-YL)-, (2R,6S)-

Systematic Name

English

KU-60019 [MI]

Common Name

English

Code System Code Type Description

CAS

925701-49-1