PH-064

PH-064 (BIM-46187) is an orally active inhibitor of the heterotrimeric G-protein complex. PH-064 inhibits SERT activity and attenuates shear stress-induced Akt phosphorylation. PH-064 has potent anti-hyperalgesia activity. PH-064 inhibits G protein-coupled receptor-dependent tumorigenesis. PH-064 can be used in the study of pain (e.g., inflammatory pain, neuropathic pain), GPCR-dependent tumors, and inflammatory lung injury^{[1][2][3][4][5][6]}. In Vitro:PH-064 (20 μM; 1 h) abrogates the flow-induced dissociation of Gαq/11 from PECAM-1 in HCAECs and attenuates shear stress-induced Akt phosphorylation^[2].
PH-064 (10 μM-100 μM; 30 min) concentration-dependently inhibits SERT-mediated 5HT uptake in mouse midbrain and frontal cortex synaptosomes, and also inhibits SERT activity in TRex-SERT cells^[3].
PH-064 (for basal IP: even at 10^-4 M) has no inhibitory effect on basal IP production in E151A-CCK2R-transfected COS cells, but completely inhibits Gastrin-stimulated IP production (EC₅₀: 34 μM)^[5].
PH-064 (10 μM; 1 h) reduces IFNγ generation in RGS2 null BMDMs to the level of WT-BMDMs without affecting BMDM viability^[6].
In Vivo:PH-064 (0.1-1 mg/kg; i.v.) elicits dose-dependent anti-hyperalgesic effect in Carrageenan (HY-125474)-induced hyperalgesia model in rats, without affecting paw oedema and motor performance^[1].
PH-064 (0.3-3 mg/kg; i.v.) shows dose-dependent anti-hyperalgesic effect in chronic constriction injury (CCI) model in rats^[1].
PH-064 (75 mg/kg; p.o.; twice a day; 16 days) exhibits antitumor activity in athymic nude mouse xenografts with E151A-CCK2R-NIH-3T3 cells without apparent toxicity^[5].
PH-064 (3 mg/kg; i.v.; 2 h after i.t. LPS) reduces IFNγ expression by 80% in RGS2 null mouse lungs and promotes resolution of lung edema^[6].