Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition.
The serine/threonine Pim 1 kinase is an oncogene whose expression is deregulated in several human cancers. Overexpression of Pim 1 facilitates cell cycle progression and suppresses apoptosis. Hence pharmacologic inhibitors of Pim 1 are of therapeutic interest for cancer. ETP-45299 is a potent and selective inhibitor of Pim 1 that inhibits the phosphorylation of Bad and 4EBP1 in cells and suppresses the proliferation of several non-solid and solid human tumor cell lines. The combination of the PI3K inhibitor GDC-0941 with ETP-45299 was strongly synergistic in MV-4-11 AML cells, indicating that the combination of selective Pim kinase inhibitors and PI3K inhibitor could have clinical benefit.
Spanish National Cancer Research Centre, Madrid, Spain.
Carmen
C
Blanco-Aparicio
Ana María García
AM
Collazo
Julen
J
Oyarzabal
Juan F
JF
Leal
María Isabel
MI
Albarán
Francisco Ramos
FR
Lima
Belén
B
Pequeño
Nuria
N
Ajenjo
Mercedes
M
Becerra
Patricia
P
Alfonso
María Isabel
MI
Reymundo
Irene
I
Palacios
Genoveva
G
Mateos
Helena
H
Quiñones
Ana
A
Corrionero
Amancio
A
Carnero
Paolo
P
Pevarello
Ana Rodríguez
AR
Lopez
Jesús
J
Fominaya
Joaquín
J
Pastor
James R
JR
Bischoff
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007191:Indazoles / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
C532162:2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; D000970:Antineoplastic Agents; C554740:ETP-45299; D004791:Enzyme Inhibitors; D007191:Indazoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011724:Pyridazines; D013449:Sulfonamides; D051573:Proto-Oncogene Proteins c-pim-1