M2698 (MSC2363318A)

Background Information:

M2698 (MSC2363318A) is an orally bioavailable, BBB penetrable
p70S6K/Akt dual inhibitor, and is highly potent in vitro (IC50 1 nM for
p70S6K, Akt1 and Akt3 inhibition; IC50 17 nM for pGSK3β indirect
inhibition) and in vivo (IC50 15 nM for pS6 indirect inhibition), and
relatively selective (only 6/264 kinases had an IC50 within 10-fold of
p70S6K). Orally administered M2698 crossed the blood-brain barrier in
rats and mice, with brain tumor exposure 4-fold higher than non-disease
brain. Dose-dependent inhibition of target substrate phosphorylation was
observed in vitro and in vivo, indicating that M2698 blocked p70S6K to
provide potent PAM pathway inhibition while simultaneously targeting Akt
to overcome the compensatory feedback loop. M2698 demonstrated
dose-dependent tumor growth inhibition in mouse xenograft models derived
from PAM pathway-dysregulated human triple-negative (MDA-MB-468) and
Her2-expressing breast cancer cell lines (MDA-MB-453 and JIMT-1), and
reduced brain tumor burden and prolonged survival in mice with
orthotopically implanted U251 glioblastoma (ref 1).

Reference:

1.A Machl, 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.
eCollection 2016.

APIM050194: M2698 (MSC2363318A)

CAS No.: 1379545-95-5.
Molecular Formula: C21H19ClF3N5O.
Molecular Weight: 734.5
Purity: 99.8-100% by achiral and chiral HPLCs.
QC: HPLC-MS, 1H-NMR, Chiral HPLC and Quantitative Elemental Analysis Report.
Solubility: Refer to Certificate of Analysis.
Storage: Refer to Certificate of Analysis.