Details
Stereochemistry | ACHIRAL |
Molecular Formula | C25H17F2N5O3S |
Molecular Weight | 505.496 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=NC=C(C=C1NS(=O)(=O)C2=CC=C(F)C=C2F)C3=CC=C4N=CC=C(C5=CC=NN=C5)C4=C3
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
Molecular Formula | C25H17F2N5O3S |
Molecular Weight | 505.496 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 | https://www.ncbi.nlm.nih.gov/pubmed/27103349Curator's Comment: Description was created based on several sources, including https://newdrugapprovals.org/2015/03/17/gsk-2126458-omipalisib-pi3kmtor-inhibitor/
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 | https://www.ncbi.nlm.nih.gov/pubmed/27103349
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26604245
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2506 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 |
0.019 nM [Ki] | ||
Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 |
0.18 nM [Ki] | ||
Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 |
0.024 nM [Ki] | ||
Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 |
0.06 nM [Ki] | ||
Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900173 |
0.13 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01725139
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25298748
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
Edited
Sat Dec 16 10:31:47 GMT 2023
by
admin
on
Sat Dec 16 10:31:47 GMT 2023
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Record UNII |
1X8F5A3NA0
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C2152
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CHEMBL1236962
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25167777
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9901
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DTXSID10148604
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1X8F5A3NA0
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C88270
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1086062-66-9
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ZZ-04
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DB12703
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300000034347
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