ONATASERTIB

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Search structure


Synonyms	ATG-008 CC-223 Cc-223 Onatasertib
Status
Molecule Category	UNKNOWN
UNII	I8RA3543SY


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

Structure


InChI Key	UFKLYTOEMRFKAD-SHTZXODSSA-N
Smiles	CO[C@H]1CC[C@H](N2C(=O)CNc3ncc(-c4ccc(C(C)(C)O)nc4)nc32)CC1
InChI	InChI=1S/C21H27N5O3/c1-21(2,28)17-9-4-13(10-22-17)16-11-23-19-20(25-16)26(18(27)12-24-19)14-5-7-15(29-3)8-6-14/h4,9-11,14-15,28H,5-8,12H2,1-3H3,(H,23,24)/t14-,15-

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C21H27N5O3
Molecular Weight	397.48
AlogP	2.48
Hydrogen Bond Acceptor	7.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	4.0
Polar Surface Area	100.47
Molecular species	NEUTRAL
Aromatic Rings	2.0
Heavy Atoms	29.0

Bioactivity

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


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	-	10	28	-	-
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase PDGFR family	-	28	-	-	-
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase VEGFR family	-	651	-	-	-
Enzyme Transferase	-	4000	18000	-	-
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel	-	33000	-	-	-
Unclassified protein	-	30	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of mTOR (unknown origin) by HTR-FRET substrate phosphorylation assay	Homo sapiens	10.0 nM
Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr	Homo sapiens	30.0 nM
Inhibition of mTORC2 in human PC3 cells assessed as inhibition of Akt phosphorylation at S473 after 1 hr	Homo sapiens	10.0 nM
In vivo inhibition of mTORC1 in human PC3 cells xenografted in mouse assessed as inhibition of S6 phosphorylation at 100 mg/kg, po measured after 4 hrs relative to control	Mus musculus	91.0 %
In vivo inhibition of mTORC1 in human PC3 cells xenografted in mouse assessed as inhibition of S6 phosphorylation at 100 mg/kg, po measured after 8 hrs relative to control	Mus musculus	92.0 %
In vivo inhibition of mTORC1 in human PC3 cells xenografted in mouse assessed as inhibition of S6 phosphorylation at 100 mg/kg, po measured after 24 hrs relative to control	Mus musculus	91.0 %
In vivo inhibition of mTORC1 in human PC3 cells xenografted in mouse assessed as inhibition of Akt phosphorylation at S473 at 100 mg/kg, po measured after 4 hrs relative to control	Mus musculus	80.0 %
In vivo inhibition of mTORC1 in human PC3 cells xenografted in mouse assessed as inhibition of Akt phosphorylation at S473 at 100 mg/kg, po measured after 8 hrs relative to control	Mus musculus	82.0 %
In vivo inhibition of mTORC1 in human PC3 cells xenografted in mouse assessed as inhibition of Akt phosphorylation at S473 at 100 mg/kg, po measured after 24 hrs relative to control	Mus musculus	86.0 %
Inhibition of Flt4 (unknown origin)	Homo sapiens	651.0 nM
Inhibition of cFMS (unknown origin)	Homo sapiens	28.0 nM
Inhibition of human mTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay	Homo sapiens	28.0 nM
Inhibition of human PI4Kbeta (1 to 828 residues) expressed in mammalian expression system by KINOMEscan assay	Homo sapiens	39.0 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	104.45 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	18.55 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	12.07 %
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	9.82 %		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	1.08 %		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	9.82 %		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	1.08 %
Inhibition of mTOR (unknown origin)	Homo sapiens	16.0 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL3586404
DrugBank	DB12570
FDA SRS	I8RA3543SY
PubChem	58298316
SureChEMBL	SCHEMBL138069
ZINC	ZINC000114617828

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).