For research use only. Not for therapeutic Use.
AT13148 is an orally active and ATP-competitive, multi-AGC kinase inhibitor with IC50s of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively.
AT13148 inhibits a panel of kinases at 10 μM, and the IC50 values for p70S6K, PKA, ROCKI, and ROCKII are all less than 10 nM and those for AKT1, 2, and 3 are 38, 402, and 50 nM, respectively. For the related AGC kinases RSK1 and SGK3, the IC50 values are 85 and 63 nM, respectively. In contrast, IC50 values for the non-AGC kinases CHK2 and Aurora B are both greater than 800 nM. AT13148 potently inhibits proliferation with GI50 values of 1.5 to 3.8 μM across a selected panel of cancer cell lines[1]. AT13148 treatment in gastric cancer cells dramatically suppresses activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3β (GSK-3β) and p90 ribosomal S6 kinase (RSK)[2].
Oral drug administration of 5 mg/kg of AT13148 results in complete bioavailability. Clear inhibition of phosphorylation of the AKT substrates GSK3β, tuberin, and the p70S6K target S6RP are also observed in PTEN-deficient MES-SA human uterine tumor xenografts after treatment with 40 and 50 mg/kg p.o. of AT13148[1]. Oral gavage of AT13148 at well-tolerated doses significantly inhibits HGC27 xenograft tumor growth in nude mice. AGC activity is also dramatically decreased in AT13148-administrated HGC27 tumors[2].
| Catalog Number | I000296 |
| CAS Number | 1056901-62-2 |
| Synonyms | (1S)-2-amino-1-(4-chlorophenyl)-1-[4-(1H-pyrazol-4-yl)phenyl]ethanol |
| Molecular Formula | C17H16ClN3O |
| Purity | ≥95% |
| InChI | InChI=1S/C17H16ClN3O/c18-16-7-5-15(6-8-16)17(22,11-19)14-3-1-12(2-4-14)13-9-20-21-10-13/h1-10,22H,11,19H2,(H,20,21)/t17-/m0/s1 |
| InChIKey | IIRWNGPLJQXWFJ-KRWDZBQOSA-N |
| SMILES | C1=CC(=CC=C1C2=CNN=C2)C(CN)(C3=CC=C(C=C3)Cl)O |
| Reference | [1]. Yap TA, et al. AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity. Clin Cancer Res. 2012 Jul 15;18(14):3912-23. [2]. Xi Y, et al. AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo. Biochem Biophys Res Commun. 2016 Sep 9;478(1):330-6 |
