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Details

Stereochemistry ACHIRAL
Molecular Formula C18H21F3N6O2
Molecular Weight 410.3942
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BUPARLISIB

SMILES

C1COCCN1c2cc(-c3c[nH]c(=N)cc3C(F)(F)F)nc(n2)N4CCOCC4

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

Molecular Formula C18H21F3N6O2
Molecular Weight 410.3942
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created using several sources including: https://www.ncbi.nlm.nih.gov/pubmed/?term=22065080 | https://www.ncbi.nlm.nih.gov/pubmed/?term=26846842

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

Curator's Comment:: BKM-120 is a CNS-penetrant in clinical trials for solid tumors, including glioblastoma. BKM-120 has potent anti-invasive effects in glioblastoma cell lines and patient-derived glioma cells in vitro.

Originator

Curator's Comment:: # Novartis

Approval Year

Targets

Targets

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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.
2011 Oct 13
Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations.
2012 Aug
Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor.
2012 Feb
Antitumor activity of NVP-BKM120--a selective pan class I PI3 kinase inhibitor showed differential forms of cell death based on p53 status of glioma cells.
2012 Jan 1
BKM-120 (Buparlisib): A Phosphatidyl-Inositol-3 Kinase Inhibitor with Anti-Invasive Properties in Glioblastoma.
2016 Feb 5
Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:40:00 UTC 2021
Edited
by admin
on Sat Jun 26 14:40:00 UTC 2021
Record UNII
0ZM2Z182GD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BUPARLISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
BKM120-AAA
Code English
NVP-BKM-120
Code English
BKM-120NX
Code English
BUPARLISIB [WHO-DD]
Common Name English
BKM120-NX
Code English
BUPARLISIB [USAN]
Common Name English
BUPARLISIB [INN]
Common Name English
BKM-120
Code English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
NCI_THESAURUS C2152
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
Code System Code Type Description
FDA UNII
0ZM2Z182GD
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
EPA CompTox
944396-07-0
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
CAS
944396-07-0
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
DRUG BANK
DB11666
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
PUBCHEM
16654980
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
CAS
1202777-78-3
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
SUPERSEDED
EVMPD
SUB128477
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
ChEMBL
CHEMBL2017974
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
NCI_THESAURUS
C90565
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
INN
9546
Created by admin on Sat Jun 26 14:40:00 UTC 2021 , Edited by admin on Sat Jun 26 14:40:00 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY