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Details

Stereochemistry ACHIRAL
Molecular Formula C25H17F2N5O3S
Molecular Weight 505.498
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OMIPALISIB

SMILES

COc1c(cc(cn1)-c2ccc3c(c2)c(ccn3)-c4ccnnc4)NS(=O)(=O)c5ccc(cc5F)F

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 505.498
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 based on several sources, including https://newdrugapprovals.org/2015/03/17/gsk-2126458-omipalisib-pi3kmtor-inhibitor/

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

Curator's Comment:: Simultaneously infused to steady state, Omipalisib (GSK2126458), dabrafenib, and trametinib, a rational combination to overcome mitogen-activated protein kinase inhibitor resistance, all had limited brain distribution in mice. In the PDX model, GSK2126458 showed efficacy in flank tumors but was ineffective in intracranial melanoma. P-gp and Bcrp are involved in limiting the brain distribution of GSK2126458.

Approval Year

Sourcing

Sourcing

Vendor/AggregatorIDURL
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

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
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 Sat Jun 26 15:04:35 UTC 2021
Edited
by admin
on Sat Jun 26 15:04:35 UTC 2021
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 Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
NCI_THESAURUS C2152
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL1236962
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
PUBCHEM
25167777
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
INN
9901
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
EPA CompTox
1086062-66-9
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
FDA UNII
1X8F5A3NA0
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
NCI_THESAURUS
C88270
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
CAS
1086062-66-9
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
DRUG BANK
DB12703
Created by admin on Sat Jun 26 15:04:35 UTC 2021 , Edited by admin on Sat Jun 26 15:04:35 UTC 2021
PRIMARY
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