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Details

Stereochemistry ACHIRAL
Molecular Formula C25H17F2N5O3S
Molecular Weight 505.496
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OMIPALISIB

SMILES

COC1=NC=C(C=C1NS(=O)(=O)C2=CC=C(F)C=C2F)C3=CC4=C(C=CN=C4C=C3)C5=CC=NN=C5

InChI

InChIKey=CGBJSGAELGCMKE-UHFFFAOYSA-N
InChI=1S/C25H17F2N5O3S/c1-35-25-23(32-36(33,34)24-5-3-18(26)12-21(24)27)11-17(13-29-25)15-2-4-22-20(10-15)19(7-8-28-22)16-6-9-30-31-14-16/h2-14,32H,1H3

HIDE SMILES / InChI

Molecular Formula C25H17F2N5O3S
Molecular Weight 505.496
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Omipalisib, also known as GSK2126458, is a small-molecule pyridylsulfonamide inhibitor of phosphatidylinositol 3-kinase (PI3K) with potential antineoplastic activity. Omipalisib (GSK2126458, GSK458) is a highly selective and potent inhibitor of p110α/β/δ/γ, mTORC1/2 with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM in cell-free assays, respectively. It is also a low picomolar inhibitor of the common activating mutants of p110a (E542K, E545K, and H1047R) found in human cancer. Omipalisib (GSK2126458) binds to and inhibits PI3K in the PI3K/mTOR signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability and inducing apoptotic cell death. Bax is a member of the proapoptotic Bcl2 family of proteins. PI3K, often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival. GlaxoSmithKline (GSK) is developing omipalisib, a phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor as well as mTOR complex 1 and 2 inhibitor, for the potential oral treatment of cancer and idiopathic pulmonary fibrosis.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin.
2010 Apr 8
Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells.
2011 Jun 1
Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner.
2012 Aug 15
[11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers.
2012 Feb 15
Patents

Sample Use Guides

In Vivo Use Guide
Subjects will be randomized in 3:1 ratio to receive Omipalisib (GSK2126458) (0.25 mg twice daily [bid]) for approximately 8 days (7 to 10 days dosing). GSK2126458 will be available as film coated tablet of dose strength 0.25 mg and 0.5 mg.
Route of Administration: Oral
In Vitro Use Guide
Morphologic derangements and apoptotic intensifications were observed in a few human tumors following in vitro treatment with GSK2126458 (50 nM for 90 min; e.g., Tumor #1, invasive ductal carcinoma).
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:04:53 UTC 2019
Edited
by admin
on Mon Oct 21 23:04:53 UTC 2019
Record UNII
1X8F5A3NA0
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OMIPALISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
OMIPALISIB [USAN]
Common Name English
OMIPALISIB [INN]
Common Name English
BENZENESULFONAMIDE, 2,4-DIFLUORO-N-(2-METHOXY-5-(4-(4-PYRIDAZINYL)-6-QUINOLINYL)-3-PYRIDINYL)-
Systematic Name English
2,4-DIFLUORO-N-(2-METHOXY-5-(4-(PYRIDAZIN-4-YL)QUINOLIN-6-YL)PYRIDIN-3-YL)BENZENESULFONAMIDE
Systematic Name English
GSK-2126458
Code English
GSK2126458
Code English
OMIPALISIB [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
NCI_THESAURUS C2152
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL1236962
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
PRIMARY
PUBCHEM
25167777
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
PRIMARY
INN
9901
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
PRIMARY
EPA CompTox
1086062-66-9
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
PRIMARY
NCI_THESAURUS
C88270
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
PRIMARY
CAS
1086062-66-9
Created by admin on Mon Oct 21 23:04:53 UTC 2019 , Edited by admin on Mon Oct 21 23:04:53 UTC 2019
PRIMARY
Related Record Type Details
ACTIVE MOIETY