KU-55933

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H17NO3S2
Molecular Weight	395.495
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1C=C(OC(=C1)C2=C3SC4=C(SC3=CC=C2)C=CC=C4)N5CCOCC5

InChI

InChIKey=XRKYMMUGXMWDAO-UHFFFAOYSA-N

InChI=1S/C21H17NO3S2/c23-14-12-16(25-20(13-14)22-8-10-24-11-9-22)15-4-3-7-19-21(15)27-18-6-2-1-5-17(18)26-19/h1-7,12-13H,8-11H2

HIDE SMILES / InChI

Molecular Formula	C21H17NO3S2
Molecular Weight	395.495
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15604286 | https://www.ncbi.nlm.nih.gov/pubmed/26575637 | http://adisinsight.springer.com/drugs/800013674

KU-55933 (2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one) is an ATP-competitive inhibitor of Ataxia telangiectasia mutated (ATM) kinase. Exposure of cells to KU-55933 resulted in a significant sensitization to the cytotoxic effects of ionizing radiation and to the DNA double-strand break-inducing chemotherapeutic agents, etoposide, doxorubicin, and camptothecin. Inhibition of ATM by KU-55933 also caused a loss of ionizing radiation-induced cell cycle arrest. By contrast, KU-55933 did not potentiate the cytotoxic effects of ionizing radiation on ataxia-telangiectasia cells, nor did it affect their cell cycle profile after DNA damage. KU55933 is a hydrophobic molecule and is insoluble in water. Nanoparticle KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine-protein kinase ATM 4 Target ID: CHEMBL3797 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15604286	Inhibitor 8504		13.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: http://adisinsight.springer.com/drugs/800013674	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion.	2016-02-01	26708502
γ-H2AX is a sensitive marker of DNA damage induced by metabolically activated 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.	2015-10	26231820
Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.	2015-09-22	26208482
Direct activation of ATM by resveratrol under oxidizing conditions.	2014	24933654
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013-04-15	23398362
The autophagy-senescence connection in chemotherapy: must tumor cells (self) eat before they sleep?	2012-12	22927544
Clioquinol induces DNA double-strand breaks, activation of ATM, and subsequent activation of p53 signaling.	2012-09-04	22627294
Progesterone and DNA damage encourage uterine cell proliferation and decidualization through up-regulating ribonucleotide reductase 2 expression during early pregnancy in mice.	2012-05-04	22403396
Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1.	2012-03-15	22226932
DNA damage responses in cells exposed to sulphur mustard.	2012-02-25	22119920
The ToxTracker assay: novel GFP reporter systems that provide mechanistic insight into the genotoxic properties of chemicals.	2012-01	22003191
Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of bisphenol A.	2012	23227178
Dynamic coregulatory complex containing BRCA1, E2F1 and CtIP controls ATM transcription.	2012	22832221
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011-10-30	22037377
DNA damage-sensing kinases mediate the mouse 2-cell embryo's response to genotoxic stress.	2011-09	21593482
5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells.	2011-08-01	21616090
Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.	2011-04-14	21413798
Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.	2011-02	21186350
Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil.	2011	22194930
ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage.	2010-12-07	21139141
Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease.	2010-11	20502937
ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress.	2010-10-08	20932476
Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells.	2010-09-01	20615625
ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation.	2010-05	20213763
DNA damage and DNA damage responses in THP-1 monocytes after exposure to spores of either Stachybotrys chartarum or Aspergillus versicolor or to T-2 toxin.	2010-05	20150440
The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt.	2010-01	20053781
Cytotoxic effects of temozolomide and radiation are additive- and schedule-dependent.	2009-12-01	19931733
The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation.	2009-11-10	19903334
ATM-dependent hyper-radiosensitivity in mammalian cells irradiated by heavy ions.	2009-09-01	19695441
Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner.	2009-08	19502594
Coactivation of ATM/ERK/NF-kappaB in the low-dose radiation-induced radioadaptive response in human skin keratinocytes.	2009-06-01	19324081
Inhibition of ataxia telangiectasia mutated kinase activity enhances TRAIL-mediated apoptosis in human melanoma cells.	2009-04-15	19351839
ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype.	2009-04-09	19098271
Cadmium-induced adaptive response in cells of Chinese hamster ovary cell lines with varying DNA repair capacity.	2009-04	19397445
DNA damage, signalling and repair after exposure of cells to the sulphur mustard analogue 2-chloroethyl ethyl sulphide.	2009-03-29	19111594
DNA double helix unwinding triggers transcription block-dependent apoptosis: a semiquantitative probe of the response of ATM, RNAPII, and p53 to two DNA intercalators.	2009-03-16	19182866
p21(WAF1/CIP1) induction by 5-azacytosine nucleosides requires DNA damage.	2008-06-05	18223691
Chk1 and Claspin potentiate PCNA ubiquitination.	2008-05-01	18451105
Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy.	2008-03-15	18347191
Growth of persistent foci of DNA damage checkpoint factors is essential for amplification of G1 checkpoint signaling.	2008-03-01	18248856
Rapid activation of ATM on DNA flanking double-strand breaks.	2007-11	17952060
Pyranone, thiopyranone, and pyridone inhibitors of phosphatidylinositol 3-kinase related kinases. Structure-activity relationships for DNA-dependent protein kinase inhibition, and identification of the first potent and selective inhibitor of the ataxia telangiectasia mutated kinase.	2007-04-19	17371003
Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homologous recombination repair, and the DNA damage response.	2007-02-01	17283137
Emerging cancer therapeutic opportunities target DNA-repair systems.	2006-06	16697054
Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair.	2006	16556909
hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage.	2005-12-16	16360036
Chronicles in drug discovery.	2005-06	16193105
Features of selective kinase inhibitors.	2005-06	15975507
ATM: HIV-1's Achilles heel?	2005-05	15867928
Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase.	2005-05	15834407

Patents

Sample Use Guides

In Vivo Use Guide

Mice bearing either H460 or A549 flank xenograft tumors received a 500 ug/kg dose of KU55933 as a free drug formulation or nanoparticle through the tail vein.

Route of Administration: Intravenous

In Vitro Use Guide

KU-55933(10 µmol/L) and sorafenib (5 µmol/L) inhibit hepatocellular carcinoma cell lines proliferation synergistically

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:11:00 GMT 2025` Edited by `admin` on `Mon Mar 31 22:11:00 GMT 2025`
Record UNII	O549494L5D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

KU55933

Preferred Name

English

KU-55933

Common Name

English

ATM KINASE INHIBITOR

Common Name

English

KU-55933 [MI]

Common Name

English

2-THIANTHREN-1-YL-6-(MORPHOLIN-4-YL)-4H-PYRAN-4-ONE

Systematic Name

English

Code System Code Type Description

SMS_ID

300000009703