VISTUSERTIB

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Search structure


Synonyms	AZD-2014 AZD2014 Azd-2014 Vistusertib
Status
Molecule Category	UNKNOWN
UNII	0BSC3P4H5X
EPA CompTox	DTXSID20143584


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

Structure


InChI Key	JUSFANSTBFGBAF-IRXDYDNUSA-N
Smiles	CNC(=O)c1cccc(-c2ccc3c(N4CCOC[C@@H]4C)nc(N4CCOC[C@@H]4C)nc3n2)c1
InChI	InChI=1S/C25H30N6O3/c1-16-14-33-11-9-30(16)23-20-7-8-21(18-5-4-6-19(13-18)24(32)26-3)27-22(20)28-25(29-23)31-10-12-34-15-17(31)2/h4-8,13,16-17H,9-12,14-15H2,1-3H3,(H,26,32)/t16-,17-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C25H30N6O3
Molecular Weight	462.55
AlogP	2.5
Hydrogen Bond Acceptor	8.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	4.0
Polar Surface Area	92.71
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	34.0

Bioactivity

Mechanism of Action	Action	Reference
Serine/threonine-protein kinase mTOR inhibitor	INHIBITOR


Protein: Serine/threonine-protein kinase mTOR Description: Serine/threonine-protein kinase mTOR Organism : Homo sapiens P42345 ENSG00000198793

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Kinase Protein Kinase Atypical protein kinase group Atypical protein kinase PIKK family Atypical protein kinase FRAP subfamily	-	3-3	0	-	-
Enzyme Transferase	-	3800	1500	-	-
Enzyme	-	3-3	0	-	-
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel	-	47500	-	-	-
Unclassified protein	-	200	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of mTORC2 in human MDA-MB-468 cells assessed as reduction of AKT phosphorylation at Ser473 after 2 hrs	Homo sapiens	80.0 nM
Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction of pS6 phosphorylation at Ser235/236 after 2 hrs	Homo sapiens	200.0 nM
Inhibition of recombinant FLAG-tagged mTOR (1362 to 2549) (unknown origin) expressed in HEK293 cells	Homo sapiens	2.8 nM
Alternative Enzyme Assay: The assay used AlphaScreen technology (Gray et al., Analytical Biochemistry, 2003, 313: 234-245) to determine the ability of test compounds to inhibit phosphorylation by recombinant mTOR.Test compounds were prepared as 10 mM stock solutions in DMSO and diluted into water as required to give a range of final assay concentrations. Aliquots (2 ul) of each compound dilution were placed into a well of a Greiner 384-well low volume (LV) white polystyrene plate (Greiner Bio-one). A 10 ul mixture of recombinant purified mTOR enzyme, 1 uM biotinylated peptide substrate (Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2; Bachem UK Ltd), ATP (20 uM) in a buffer solution [comprising Tris-HCl pH7.4 buffer (50 mM), EGTA (0.1 mM), bovine serum albumin (0.5 mg/ml), DTT (1.25 mM) and manganese chloride (10 mM)] were added to the assay plates and incubated with compound for 2 hours at room temperature.	Homo sapiens	20.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	Homo sapiens	983.0 nM
Competitive inhibition of human mTOR using 4EBP1 as substrate in presence of [33gammaP]-ATP after 120 mins by filter binding method	Homo sapiens	2.8 nM
Inhibition of human mTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay	Homo sapiens	0.14 nM
Inhibition of human PI3Kalpha (108 to 1068 residues) expressed in mammalian expression system by KINOMEscan assay	Homo sapiens	33.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging	Homo sapiens	112.0 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	-14.63 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	-24.53 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	3.79 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	3.99 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	3.99 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	3.79 %

Related Entries

Cross References

Resources	Reference
ChEMBL	CHEMBL2336325
DrugBank	DB11925
FDA SRS	0BSC3P4H5X
Guide to Pharmacology	7699
PubChem	25262792
SureChEMBL	SCHEMBL290672
ZINC	ZINC000059258964

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).