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Details

Stereochemistry ACHIRAL
Molecular Formula C18H21F3N6O2
Molecular Weight 410.3935
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BUPARLISIB

SMILES

NC1=NC=C(C2=CC(=NC(=N2)N3CCOCC3)N4CCOCC4)C(=C1)C(F)(F)F

InChI

InChIKey=CWHUFRVAEUJCEF-UHFFFAOYSA-N
InChI=1S/C18H21F3N6O2/c19-18(20,21)13-9-15(22)23-11-12(13)14-10-16(26-1-5-28-6-2-26)25-17(24-14)27-3-7-29-8-4-27/h9-11H,1-8H2,(H2,22,23)

HIDE SMILES / InChI

Description

Buparlisib (NVP-BKM12), a dimorpholino pyrimidine derivative, is a selective pan class I phosphatidylinositol-3 kinase (PI3K) inhibitor for treating cancer. It penetrates the blood-brain barrier and has a potential as a glioma treatment. NVP-BKM120 inhibits PI3K activity by binding to the ATP binding cleft of this enzymes and was tested against class I PI3K and other kinases using an ATP depletion (Kinase-Glo) assay. The compound was shown to be active against P110 α, β, γ and δ. The inhibition of the PI3K signaling pathways leads to different forms of cell death on the basis of p53 statuses. Buparlisib demonstrated its activity in human glioblastoma (GBM) cells in vitro and in vivo and is in clinical trials for solid tumors including GBM.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
35.0 nM [IC50]
175.0 nM [IC50]
348.0 nM [IC50]
108.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
In diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease or after one or two prior antineoplastic therapy lines for metastatic disease buparlisib was administered in on a continuous once daily dosing schedule at a dose of 100 mg. The patient was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area.
Route of Administration: Oral
In Vitro Use Guide
The biologic effects of a selective PI3K inhibitor NVP-BKM120 (Buparlisib) were studied in a set of 21 glioma cell lines that differed in terms of the mutational statuses of PTEN and p53. Cells treatment for 72 hours resulted in a dose-dependent growth inhibition and effectively blocked the PI3K/Akt signaling cascade. NVP-BKM120 potently inhibited glioma cell proliferation in all the lines, with IC50 values in the cell viability assay of 1 to 2 uM.