BYL-719

Reagent Authentication Certificate:

Chemical Probes Portal BYL-719.pdf

Protein target name:

PIK3CA

Mechanism of action:

ATP-competitive inhibitor

Recommended Concentration for use in cells:

10 nM - 1 uM

Probe Availability

MedChem Express (1217486-61-7)

Cayman (1217486-61-7)

Probe Information

Target and Probe Information

Target Details

Target class:

Lipid kinase

Subclass:

Class I

HUGO ID:

HGNC:8975

Entrez gene ID:

5290

UNIPROT ID:

P42336

Target alias:

PI3K, p50alpha, p55alpha, p85alpha

Probe Details

Chemical Probes Portal ID:

CPP100

Probe alias:

Alpelisib, 1217486-61-7, NVP-BYL719, BYL719

PubChem CID:

56649450

ChEMBL ID:

CHEMBL2396661

SMILES string:

CC1=C(SC(=N1)NC(=O)N2CCC[C@H]2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F

InChi Key:

STUWGJZDJHPWGZ-LBPRGKRZSA-N

Orthogonal probe:

Pictilisib

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

0.005 uM

Potency assay:

In vitro kinase assay

PDB ID for probe-target interaction (3D structure):

4JPS

Structure-activity relationship:

Attaching a (S)-pyrrolidine carboxamide moiety to the 2-amino group through an urea linkage confers selectivity for the alpha isoform.

Off target activity

Potency (off target):

IC50

Off target protein and potency:

PIK3CB 1.2 uMPIK3CD 0.29 uMPIK3CG 0.25 uM

Potency assay (off target):

In vitro kinase assay. BYL-719 was >50-fold selective of PIK3CA over 442 kinases in vitro (Ambit). IC50 > 9 for VPS34, MTOR, DNA-PK, and ATR.

Probe Selectivity in Vitro:

IC50 for CYP450A > 10 uM

In cell validation

On target activity in cells

Potency in cells:

IC50

0.074 uM

Potency assay (cells):

Substrate phosphorylation in Rat1-myr-p110alpha cells

Target engagement assay (cells):

Indirect: inhibition of substrate phosphorylation

Off target activity in cells

Potency in cells, off target:

IC50

Off target protein and potency (cells):

PI3KCB 2.2 uMPI3KCD 1.2 uM

In vivo validation

Organism:

Sprague-Dawley rats

Dose:

1 mg/kg

Route of delivery:

Intravenous

Plasma half life:

2. 9 hr

Systemic clearance:

10 mL/min/kg

Fraction of probe bound to plasma protein:

0.94

Cmax:

0.19 uM

Primary Reference

Reference (doi):

10.1016/j.bmcl.2013.05.007

Reference (PMID):

23726034

BYL-719

Probe Availability

Probe Information

Target Details

PI3K, p50alpha, p55alpha, p85alpha

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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BYL-719

Probe Availability

Probe Information

Target Details

PI3K, p50alpha, p55alpha, p85alpha

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?