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LY3023414

Cat. No. M8925
LY3023414 Structure
Size Price Availability Quantity
10mg USD 200 In stock
50mg USD 780 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

LY3023414 potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC50s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively.

In vitro, inhibition of PI3K/AKT/mTOR signaling by LY3023414 causes G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In cell-based assays, LY3023414 inhibition of PI3K and mTOR is assessed in the PTEN-deficient U87 MG glioblastoma cell line. LY3023414 inhibits the phosphorylation of AKT at position T308 downstream of PI3K at an IC50 of 106 nM.

In vivo, LY3023414 (3, 6, or 10 mg/kg) twice daily orally for 28 days results in dose-responsive inhibition of tumor growth in the PTEN-deleted U87 MG xenograft model. This treatment produces similar TGI in models exhibiting PTEN truncation (786-O), activating PI3Kα mutation (NCI-H1975), and transgenic Eμ-myc mutant PI3Kα-driven leukemia models. Of note, the total daily dose of LY3023414 appears to result in equipotent antitumor activity: 12 mg/kg once daily and 6 mg/kg twice daily produces similar delta T/C values (42% and 38%, respectively) in U87 MG.

Customer Product Validations & Biological Datas
Source Oncotarget (2016 Nov). Figure 5. LY3023414
Method RNA-Seq analysis
Cell Lines BLCAb001 and BLCAb002 derived cells
Concentrations 0, 15, 120 nM
Incubation Time
Results Our RNAseq data showed BNIP3 and BCL11A upregulation, and ULK2, BAG1, RAB11FIP4 and BCLL14 downregulation in BLCAb001 tumors, mirroring the higher levels of LC3B I/II by Western blot analysis (Figure 5A and 5B).
Protocol
Cell Experiment
Cell lines RKO and SK-OV-3 cells; MOLT-4 and L-363 cells; DLD-1, HCT-116, HCT-15, and NCI-H460 cells
Preparation method The CellTiter-Glo luminescent cell viability assay system is used to measure the antiproliferative effects of LY3023414 after 2 cell doublings on cells plated on plastic or incubated for 2 weeks in soft agar with a collection of standard cell lines and human patient–derived tumor xenografts passaged in nude mice. For the soft-agar assay, RKO and SK-OV-3 cells; MOLT-4 and L-363 cells; DLD-1, HCT-116, HCT-15, and NCI-H460 cells are used. These standard cell lines are genotyped by STR and matched to existing STR reference genotypes. Oncotest PDX models (including model MX1 originally derived at NCI) are characterized using the Affymetrix genome-wide human SNP Array 6.0 as well as whole-exome sequencing. Genetic identity analysis confirm that all PDX models are derived from independent patient samples. Combination studies are conducted in which LY3023414 is mixed with other therapeutic agents in fixed ratios of concentrations corresponding to the IC50 equivalents of each single agent. The combination index at 50% inhibition (CI50) is calculated.
Concentrations
Incubation time
Animal Experiment
Animal models athymic nude, CD-1 nude and NMRI athymic nude mice(Xenograft tumors)
Formulation 1% HEC in distilled water containing 0.25% polysorbate 80 and 0.05% Dow-Corning Antifoam 1510-US
Dosages
Administration p.o.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 406.48
Formula C23H26N4O3
CAS Number 1386874-06-1
Purity >99%
Solubility DMSO: 40 mg/mL
Storage at -20°C
References

Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts.
Wei L, et al. Oncotarget. 2016 Nov 22;7(47):76374-76389. PMID: 27823983.

Characterization of LY3023414, a Novel PI3K/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth.
Smith MC, et al. Mol Cancer Ther. 2016 Oct;15(10):2344-2356. PMID: 27439478.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: LY3023414 supplier, PI3K, inhibitors

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