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.
Chemical Formula: C21H17NO3S2
Exact Mass: 395.06498
Molecular Weight: 395.49
Elemental Analysis: C, 63.77; H, 4.33; N, 3.54; O, 12.14; S, 16.22
InChi Code: 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
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
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.
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Pizarro JG, Folch J, de la Torre AV, Junyent F, Verdaguer E, Jordan J, Pallas
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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.
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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