| Identification | Back Directory | [Name]
2-(4-PIPERAZINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE DIHYDROCHLORIDE | [CAS]
854127-90-5 | [Synonyms]
LY-303,511 dihydrochloride
8-phenyl-2-piperazin-1-ylchromen-4-one:dihydrochloride
2-(4-PIPERAZINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE DIHYDROCHLORIDE | [Molecular Formula]
C19H20Cl2N2O2 | [MDL Number]
MFCD06801360 | [MOL File]
854127-90-5.mol | [Molecular Weight]
379.28 |
| Hazard Information | Back Directory | [Description]
LY303511 is a close structural analog of LY294002 , a selective phosphatidylinositol 3-kinase (PI3K) inhibitor.1 LY303511, however, does not inhibit PI3K-dependent phosphorylation of Akt but instead has been shown to inhibit mTOR-dependent phosphorylation of S6K.1 It can reduce cell proliferation in human lung epithelial adenocarcinoma cells, blocking G2/M progression and inhibiting casein kinase 2 activity.1 LY303511 demonstrates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitizing activity in HeLa cells that are refractory to TRAIL-induced apoptosis.2 LY303511 is also reported to block voltage-gated potassium (Kv) channels.3 | [Uses]
LY 303511 dihydrochloride is a structural analogue of LY294002. LY 303511 dihydrochloride does not inhibit PI3K. LY 303511 dihydrochloride enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells. LY 303511 dihydrochloride reversibly blocks K+ currents (IC50=64.6±9.1 μM) in MIN6 insulinoma cells. | [in vivo]
Intraperitoneal administration of vehicle or LY 303511 dihydrochloride (10 mg/kg/day) is performed when tumors reach a volume of ~150 mm3, at which time 35 mice have developed a tumor. After 21 days, >15% of the mice require euthanasia because of excessive tumor growth, and these data are censored due to unreliable estimates of average tumor volume. The administration of LY 303511 dihydrochloride, 10 mg/kg/day, is sufficient to inhibit PC-3 tumor growth in vivo[4]. | [References]
1. Kristof, A.S., Pacheco-Rodriguez, G., Schremmer, B., et al. LY303511 (2-piperazinyl-8-phenyl-4H-1-benzopyran-4-one) acts via phosphatidylinositol 3-kinase-independent pathways to inhibit cell proliferation via mammalian target of rapamycin (mTOR)- and non-mTOR-dependent mechanisms J. Pharmacol. Exp. Ther. 314(3),1134-1143(2005).
2. Mellier, G., Liu, D., Bellot, G., et al. Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27 Cell Death Dis. 4,e890(2013).
3. Pattnaik, B.R., and Hughes, B.A. Regulation of Kir channels in bovine retinal pigment epithelial cells by phosphatidylinositol 4,5-bisphosphate Am. J. Physiol. Cell Physiol. 297(4),C1001-C1011(2009). |
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