GS-9901

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Search structure


Synonyms	Gs 9901 Gs-9901
Status
Molecule Category	UNKNOWN
UNII	U09Q76B8VK


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	XDSXYMOZKDUASY-INIZCTEOSA-N
Smiles	N#Cc1c(N)nc(N)nc1N[C@H](c1nc2c(F)ccc(Cl)c2c(=O)n1-c1cccnc1)C1CC1
InChI	InChI=1S/C22H17ClFN9O/c23-13-5-6-14(24)17-15(13)21(34)33(11-2-1-7-28-9-11)20(30-17)16(10-3-4-10)29-19-12(8-25)18(26)31-22(27)32-19/h1-2,5-7,9-10,16H,3-4H2,(H5,26,27,29,31,32)/t16-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C22H17ClFN9O
Molecular Weight	477.89
AlogP	2.96
Hydrogen Bond Acceptor	10.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	5.0
Polar Surface Area	161.42
Molecular species	NEUTRAL
Aromatic Rings	4.0
Heavy Atoms	34.0

Assay Description	Organism	Bioactivity	Reference
Time-Resolved Fluorescence Resonance Energy transfer (TR-FRET) Assay: Class I PI3K isoforms were expressed and purified as heterodimeric recombinant proteins. All assay reagents and buffers for the TR-FRET assay were purchased from Millipore. PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2× Km ATP (75-500 μM), 2 μM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 1% (v/v) DMSO at the following concentrations for each isoforms: PI3Kα, PI3Kβ, and PI3Kδ between 25 and 50 pM, and PI3Kγ at 2 nM. After an assay reaction time of 30 minutes at 25° C., reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIP3, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 10lps delay and 500 μs read window).	Homo sapiens	1.0 nM
Inhibition of human full length PI3K p110delta/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay	Homo sapiens	1.0 nM
Inhibition of human full length PI3K p110alpha/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay	Homo sapiens	750.0 nM
Inhibition of recombinant human full-length N-terminal His-tagged PI3K p110beta/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay	Homo sapiens	100.0 nM
Inhibition of human full length PI3K p110gamma using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay	Homo sapiens	190.0 nM
Inhibition of PI3Kdelta in human whole blood assessed as reduction in anti-FCepsilonR1 mAb-stimulated basophil activation preincubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation and measured after 25 mins by flow cytometry analysis	Homo sapiens	1.0 nM
Inhibition of PI3K p110delta in human basophil assessed as reduction in anti-FCepsilonR1 mAb-stimulated basophil activation preincubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation and measured after 25 mins by flow cytometry analysis	Homo sapiens	0.31 nM
Inhibition of PI3K p110beta in human PC-3 cells assessed as reduction in AKT phosphorylation at S473 residue measured after 2 hrs by TR-FRET analysis	Homo sapiens	42.0 nM
Inhibition of PI3K p110gamma in human basophil assessed as reduction in fMLP-induced basophil activation by flow cytometry analysis	Homo sapiens	403.6 nM
Inhibition of PI3K p110delta in human basophil assessed as reduction in anti-FCepsilonR1 mAb-induced basophil activation preincubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation and measured after 25 mins in presence of 25% serum by flow cytometry analysis	Homo sapiens	1.3 nM
Inhibition of PI3K p110gamma in human basophil assessed as reduction in fMLP-induced basophil activation in presence of 25% serum by flow cytometry analysis	Homo sapiens	581.0 nM
Inhibition of PI3Kdelta in human whole blood assessed as inhibition of BCR-induced B-cell activation	Homo sapiens	2.4 nM
Inhibition of PI3Kdelta in rat whole blood assessed as reduction in anti-IgD induced basophil activation by measuring decrease in CD86 surface expression by flow cytometry analysis	Rattus norvegicus	1.6 nM
In vivo inhibition of PI3Kdelta in Lewis rat model of Freund's incomplete adjuvant-induced arthritis at 0.3 mg/kg, po bid administered for 7 days at 12 hrs interval starting from day 10 to day 16 post-immunization relative to control	Rattus norvegicus	60.0 %
In vivo inhibition of PI3Kdelta in Lewis rat model of Freund's incomplete adjuvant-induced arthritis at 1 mg/kg, po bid administered for 7 days at 12 hrs interval starting from day 10 to day 16 post-immunization relative to control	Rattus norvegicus	80.0 %
In vivo inhibition of PI3Kdelta in Lewis rat model of Freund's incomplete adjuvant-induced arthritis at 3 mg/kg, po bid administered for 7 days at 12 hrs interval starting from day 10 to day 16 post-immunization relative to control	Rattus norvegicus	90.0 %

Cross References

Resources	Reference
ChEMBL	CHEMBL3928407
FDA SRS	U09Q76B8VK
PDB	77C
PubChem	86763204
ZINC	ZINC000220883766

CONTENTS

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).