Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C19H26N6O |
Molecular Weight | 354.4493 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC[C@@H](CO)NC1=NC2=C(N=CN2C(C)C)C(NCC3=CC=CC=C3)=N1
InChI
InChIKey=BTIHMVBBUGXLCJ-HNNXBMFYSA-N
InChI=1S/C19H26N6O/c1-4-15(11-26)22-19-23-17(20-10-14-8-6-5-7-9-14)16-18(24-19)25(12-21-16)13(2)3/h5-9,12-13,15,26H,4,10-11H2,1-3H3,(H2,20,22,23,24)/t15-/m0/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/23274706
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23274706
(S)-Seliciclib is enantiomer of the potent cyclin-dependent kinase (CDK) inhibitor Roscovitine. Roscovitine (racemic mixture) is an inhibitor of cell cyclin-dependent kinase (CDK)-2, CDK-4 and CDK-5, which are upregulated in stress conditions inducing apoptosis. (S)-Seliciclib potently inhibits Cyclin-dependent kinase 1. In vivo studies in rabbits demonstrated that both isomers (R- and S-) significantly reduce intraocular pressure (IOP). However, S- isomer was superior to R- isomer in lowering IOP and providing protection to retinal ganglionic cells.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9046330 |
550.0 nM [IC50] | ||
Target ID: CHEMBL4478 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24936234 |
570.0 µM [EC50] | ||
Target ID: CHEMBL4036 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20711428 |
350.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23274706
New Zealand White (albino) rabbits were used for activity evaluation. (S)-Seliciclib Was suspended in 4% (w/v) polyethylene glycol (PEG) 4000 at a concentration of 0.1%. Drug solution (50 mkL) was topically administered in the left eyes.
Route of Administration:
Topical
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23274706
The cultured retinal ganglion cell (RGC-5) line were used for activity evaluation. Cultures were maintained at 37 C in a humidified atmosphere of 95% air and 5% CO2. The RGC-5 cells were passaged by trypsinization every 3–4 days. The oxygen–glucose deprivation (OGD)-induced cell death assay involved seeding the cells at a density of 2 x 10^3 cells per well into 96-well plates, followed by incubation in a humidified atmosphere of 95% air and 5% CO2 at 37 C for 24 h. The OGD stress was induced by washing the cells with glucose-free DMEM (Invitrogen, Carlsbad, CA, USA) and then placing them in the same medium in a hypoxic incubator (94% N2, 5% CO2, and 1% O2) for 4 h. At the end of the OGD period, glucose solution and FBS were added at final concentrations of 4.5 mg/mL and 1%, respectively, and the cultures were returned to the incubator for an additional 16 h at the regular atmospheric oxygen level (reoxygenation). The roscovitine R-isomer or S-isomer ((S)-Seliciclib) was added to the culture immediately after replacement of the culture medium. At the end of this culture period, the cell viability was measured.
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8C43G94891
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6603989
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m9849
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186692-45-5
Created by
admin on Sat Dec 16 10:00:29 GMT 2023 , Edited by admin on Sat Dec 16 10:00:29 GMT 2023
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SUBSTANCE RECORD