M2698

• CAT Number: I016701
• CAS Number: 1379545-95-5
• Molecular Formula: C21H19ClF3N5O
• Molecular Weight: 449.86
• Purity: ≥95%
• Synonyms: 4-[[(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide
• InChI: InChI=1S/C21H19ClF3N5O/c22-16-6-5-12(9-15(16)21(23,24)25)17(10-30-7-2-8-30)29-20-14-4-1-3-13(19(26)31)18(14)27-11-28-20/h1,3-6,9,11,17H,2,7-8,10H2,(H2,26,31)(H,27,28,29)/t17-/m1/s1
• InChIKey: HXAUJHZZPCBFPN-QGZVFWFLSA-N
• SMILES: C1CN(C1)CC(C2=CC(=C(C=C2)Cl)C(F)(F)F)NC3=NC=NC4=C3C=CC=C4C(=O)N

M2698 (MSC2363318A) is an orally active, ATP competitive, selective p70S6K and Akt dual-inhibitor with IC50s of 1 nM for p70S6K, Akt1 and Akt3. M2698 can cross the blood-brain barrier and has anti-cancer activity[1].
M2698 (0.3 nM to 50 M; 72 hours) inhibits proliferation in a dose-dependent manner in breast tumors cell lines with IC50s of 0.02-8.5 μM[1]. ?
M2698 (0.3, 1 μM; 24 hours) inhibits p70S6K activity and induces feedback loop phosphorylation on Akt and suppresses Akt activity in breast cancer cell lines[1]. ?
M2698 inhibits indirectly pGSK3β (IC50=17 nM) and pS6 (IC50=15 nM)[1].
M2698 (10-30 mg/kg/day; PO; 28 days) results in dose-dependent inhibition of tumor growth and results in tumor regression with the highest dose of 30 mg/kg[1]. ?
M2698 (20 mg/kg/day; PO; 4 days) has a tumor:plasma exposure ratio of 12:1 over 24 hours and leads to increased levels of pAkt in tumor tissue[1]. ?
The mean total concentration of M2698 after 16-hour infusion in rats is 1750 ng/g and 175 ng/mL in brain and plasma, respectively[1]. ?
M2698 (po; 1, 5, 10, or 20 mg/kg/day; for 7 days) inhibits the phosphorylation of S6 in a dose-proportional manner over time after a single administration or daily treatments over 7 days[1].

Reference

[1]. Machl A, et al. M2698 is a potent dual-inhibitor of p70S6K and Akt that affects tumor growth in mouse models of cancer and crosses the blood-brain barrier. Am J Cancer Res. 2016 Mar 15;6(4):806-18.
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