PP121

Research use only, not for human use.

A multitargeted, dual tyrosine and PI3K kinase inhibitor of PDGFR, Hck, mTOR, VEGFR2, Src and Abl.

A multitargeted, dual tyrosine and PI3K kinase inhibitor of PDGFR, Hck, mTOR, VEGFR2, Src and Abl with IC50 of 2, 8, 10, 12, 14 and 18 nM; also inhibits Ret, VEGFR-2, 110α/mTOR, potently inhibits both tyrosine kinases and PI3Ks but not serine-threonine kinases.

PP121 blocks the PI3K pathway by direct inhibition of PI3K/mTOR in two glioblastoma cell lines, U87 and LN229. PP121 potently inhibits the proliferation of a diverse panel of tumor cell lines containing mutations in the PI3-K pathway components PIK3CA, PTEN, or RAS. PP121 induces a G0G1 arrest in most tumor cells. PP121 directly inhibits Src in cells and reverses its biochemical and morphological effects. PP121 potently inhibits the Ret kinase domain in vitro (IC50<1 nM). PP121 potently blocks VEGF stimulated activation of the PI3-K and MAPK pathways. PP121 inhibits VEGFR2 autophosphorylation at low nanomolar concentrations, confirming that this molecule directly targets VEGFR2 in cells. PP121 inhibits Bcr-Abl induced tyrosine phosphorylation in K562 cells as well as BaF3 cells that express Bcr-Abl.

Oral administration of PP121 remarkably inhibits Eca-109 xenograft growth. Mice body weights are not significantly affected by PP121 or the vehicle treatment. PP121 oral administration dramatically inhibits activations of Akt-mTOR and NFkB in xenograft tumors. p-Akt Ser 473 and p-IKKa/b are both inhibited by PP121 administration.

PP 121 | PP-121

PI3K/Akt/mTOR signaling

PI3K

Hck|mTOR|PDGFR|Src|VEGFR

Cancer

——

1092788-83-4

319.3638

C17H17N7

>98% (HPLC)

10 mM in DMSO

NC1=C2C(N(C3CCCC3)N=C2C4=CN=C(NC=C5)C5=C4)=NC=N1

1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 1-cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-

(-20℃)

With Ice Pack

≥ 2 years