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LY-303511, also known as NV-128 and EM 101, is a potent mTOR inhibitor. LY-303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors. LY-303511 amplifies TRAIL-induced apoptosis in tumor cells by enhancing DR5 oligomerization, DISC assembly, and mitochondrial permeabilization. LY-303511 acts via phosphatidylinositol 3-kinase-independent pathways to inhibit cell proliferation via mammalian target of rapamycin (mTOR)- and non-mTOR-dependent mechanisms.

Product information

CAS Number: 154447-38-8

Molecular Weight: 306.36

Formula: C19H18N2O2


LY 303511





NV 128


EM 101


Chemical Name: 2-(1-Piperazinyl)-8-phenyl-4H-1-benzopyran-4-one

Smiles: O=C1C=C(OC2C1=CC=CC=2C1C=CC=CC=1)N1CCNCC1


InChi: InChI=1S/C19H18N2O2/c22-17-13-18(21-11-9-20-10-12-21)23-19-15(7-4-8-16(17)19)14-5-2-1-3-6-14/h1-8,13,20H,9-12H2

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

LY-303511 is structurally identical to LY294002 except for a substitution of -O for -NH in the morpholine ring, and does not potently inhibit PI3K. Treatment of cells with LY-303511 causes an increase in calcein spread similar to levels of LY294002. The ability of LY-303511 to increase gap junctional intercellular communication (GJIC) does not occur concomitant with inhibition of phosphorylation of AKT as measured by immunoblotting. LY-303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via H2O2-MAPK activation and up-regulation of death receptors. SHEP-1 cells are exposed to varying concentrations of LY-303511 (LY30), TRAIL, and a combination of the two (1 h preincubation with LY-303511 followed by TRAIL for 4 hours). SHEP-1 cells are responsive to TRAIL (~10%, ~15%, and ~30% reduction in the surviving fraction at 25, 50, and 100 ng/mL, respectively); however, treatment with LY-303511 (12.5, 25, or 50 μM) has no effect on cell viability. However, incubation of cells with LY-303511 (25 μM) for 1 hour followed by 4 hours exposure to 50 ng/mL of TRAIL has a strong synergistic effect (~40% reduction in viable cells with LY-303511+TRAIL versus ~15% with TRAIL alone). LY-303511 is a negative control compound with respect to PI3K activity. In MIN6 insulinoma cells, Wortmannin (100 nM) has no effect on whole-cell outward K+ currents, but LY294002 and LY-303511 reversibly block currents in a dose-dependent manner (IC50=9.0±0.7 μM and 64.6±9.1 μM, respectively). Kv2.1 and Kv1.4 are highly expressed in beta-cells, and in Kv2.1-transfected tsA201 cells, 50 μM LY294002 and 100 μM LY-303511 reversibly inhibit currents by 99% and 41%, respectively. LY-303511 blocks currents with an IC50 of 64.6±9.1 µM, with a maximal inhibition of ~90% at 500 µM (n≥5 cells at each concentration).

In Vivo:

Intraperitoneal administration of vehicle or LY-303511 (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, 10 mg/kg/day, is sufficient to inhibit PC-3 tumor growth in vivo.


  1. Shi Y, Mellier G, Huang S, White J, Pervaiz S, Tucker-Kellogg L. Computational modelling of LY303511 and TRAIL-induced apoptosis suggests dynamic regulation of cFLIP. Bioinformatics. 2013 Feb 1;29(3):347-54. doi: 10.1093/bioinformatics/bts702. Epub 2012 Dec 13. PubMed PMID: 23239672; PubMed Central PMCID: PMC3562069.
  2. Tucker-Kellogg L, Shi Y, White JK, Pervaiz S. Reactive oxygen species (ROS) and sensitization to TRAIL-induced apoptosis, in Bayesian network modelling of HeLa cell response to LY303511. Biochem Pharmacol. 2012 Nov 15;84(10):1307-17. doi: 10.1016/j.bcp.2012.08.028. Epub 2012 Sep 6. PubMed PMID: 22982511.

Products are for research use only. Not for human use.

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