Ku-55933


Catalog No. size PriceQuantity
M6440-2 2mg solid $76
M6440-10 10mg solid $312

Description

KU-55933 is an ATM inhibitor, which blocks the phosphorylation of Akt induced by insulin and insulin-like growth factor I in cancer cells that exhibit abnormal Akt activity. Moreover, KU-55933 inhibits cancer cell proliferation by inducing G(1) cell cycle arrest. It does so through the downregulation of the synthesis of cyclin D1, a protein known to be elevated in a variety of tumors. In addition, KU-55933 treatment during serum starvation triggers apoptosis in these cancer cells. Research results suggest that KU-55933 may be a novel chemotherapeutic agent targeting cancer resistant to traditional chemotherapy or immunotherapy due to aberrant activation of Akt. Furthermore, KU-55933 completely abrogates rapamycin-induced feedback activation of Akt. Combination of KU-55933 and rapamycin not only induces apoptosis, which is not seen in cancer cells treated only with rapamycin, but also shows better efficacy in inhibiting cancer cell proliferation than each drug alone. For detail see: http://www.ncbi.nlm.nih.gov/pubmed/20053781.

Product information

CAS Number: 587871-26-9

Molecular Weight: 395.49

Formula: C21H17NO3S2

Synonym:

KU 55933

KU55933

Chemical Name: 2-morpholino-6-(thianthren-1-yl)-4H-pyran-4-one

Smiles: O=C1C=C(OC(=C1)N1CCOCC1)C1=CC=CC2SC3=CC=CC=C3SC=21

InChiKey: XRKYMMUGXMWDAO-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

KU-55933 (10 μM) blocks the ionizing radiation-induced p53 serine 15 phosphorylation. KU-55933 has a dose-dependent effect in inhibiting this ATM-dependent phosphorylation event with an estimated IC50 of 300 nM. KU-55933 ablates the ionizing radiation-induced phosphorylation of these ATM substrates. KU-55933 specifically inhibits ATM but not the other DNA damage-activated PIKKs, ATR, and DNA-PK. KU-55933 induces pATM, p53, E2F1 and pATR, noticeably upregulates the nuclear fraction of E2F1 at the 0.5 h time point. Metformin increases ATM and AMPK phosphorylation, as well as SHP protein level in primary hepatocytes, and this stimulatory effect of metformin is repressed by a specific ATM kinase inhibitor KU-55933.

References:

  1. Camins A, Pizarro JG, Alvira D, Gutierrez-Cuesta J, de la Torre AV, Folch J, Sureda FX, Verdaguer E, Junyent F, Jordán J, Ferrer I, Pallàs M. Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease. Cell Mol Life Sci. 2010 May 26. [Epub ahead of print] PubMed PMID: 20502937.
  2. Pizarro JG, Folch J, de la Torre AV, Junyent F, Verdaguer E, Jordan J, Pallas M, Camins A. ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation. J Cell Biochem. 2010 May;110(1):210-8. PubMed PMID: 20213763.
  3. Rakkestad KE, Skaar I, Ansteinsson VE, Solhaug A, Holme JA, Pestka JJ, Samuelsen JT, Dahlman HJ, Hongslo JK, Becher R. 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. Toxicol Sci. 2010 May;115(1):140-55. Epub 2010 Feb 11. PubMed PMID: 20150440.
  4. Li Y, Yang DQ. The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt. Mol Cancer Ther. 2010 Jan;9(1):113-25. Epub 2010 Jan 6. PubMed PMID: 20053781.
  5. Chalmers AJ, Ruff EM, Martindale C, Lovegrove N, Short SC. Cytotoxic effects of temozolomide and radiation are additive- and schedule-dependent. Int J RadiatOncol Biol Phys. 2009 Dec 1;75(5):1511-9. PubMed PMID: 19931733.
  6. Golding SE, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA, O'Connor MJ, Povirk LF, van MeterT, Valerie K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902. Epub 2009 Oct 6. PubMed PMID: 19808981; PubMed Central PMCID: PMC2761990.
  7. Xue L, Yu D, Furusawa Y, Cao J, Okayasu R, Fan S. ATM-dependent hyper-radiosensitivity in mammalian cells irradiated by heavy ions. Int J RadiatOncol Biol Phys. 2009 Sep 1;75(1):235-43. PubMed PMID: 19695441.

Products are for research use only. Not for human use.

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