ONVANSERTIB

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Search structure


Synonyms	NMS-1286937 NMS-P937 Nms-1286937 Onvansertib PCM-075
Status
Molecule Category	UNKNOWN
UNII	67RM91WDHQ


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

Structure


InChI Key	QHLVBNKYJGBCQJ-UHFFFAOYSA-N
Smiles	CN1CCN(c2ccc(OC(F)(F)F)c(Nc3ncc4c(n3)-c3c(c(C(N)=O)nn3CCO)CC4)c2)CC1
InChI	InChI=1S/C24H27F3N8O3/c1-33-6-8-34(9-7-33)15-3-5-18(38-24(25,26)27)17(12-15)30-23-29-13-14-2-4-16-20(22(28)37)32-35(10-11-36)21(16)19(14)31-23/h3,5,12-13,36H,2,4,6-11H2,1H3,(H2,28,37)(H,29,30,31)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C24H27F3N8O3
Molecular Weight	532.53
AlogP	1.92
Hydrogen Bond Acceptor	10.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	7.0
Polar Surface Area	134.66
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	38.0

Bioactivity

Mechanism of Action	Action	Reference
Serine/threonine-protein kinase PLK1 inhibitor	INHIBITOR	PubMed PubMed

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Kinase Protein Kinase CAMK protein kinase group CAMK protein kinase CAMK1 family CAMK protein kinase MELK subfamily	-	744	-	-	-
Enzyme Kinase Protein Kinase Other protein kinase group Other protein kinase PLK family	-	2	-	-	-
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase PDGFR family	-	510	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of PLK1 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	None	2.0 nM
Antiproliferative activity against human A2780 cells	Homo sapiens	42.0 nM
Inhibition of FLT3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	None	510.0 nM
Inhibition of MELK assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	None	744.0 nM
Inhibition of CK2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	None	826.0 nM
Biochemical Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds were determined using a trans-phosphorylation assay.Specific peptide or protein substrates are trans-phosphorylated by their specific serine-threonine or tyrosine kinase, in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors.At the end of the phosphorylation reaction, more than 98% cold ATP and radioactive ATP is captured by an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity.Supernatant, containing the phosphorylated substrate, is subsequently withdrawn and transferred into a counting plate, then evaluated by beta-counting.Reagents/Assay Conditions i. Dowex Resin Preparation500 g of wet resin (SIGMA, custom prepared resin DOWEX 1x8 200-400 mesh, 2.5 Kg) are weighed out and diluted to 2 L in 150 mM sodium formate, pH 3.00.The resin is allowed to settle down.	Homo sapiens	3.0 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	-4.32 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	19.88 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	20.8 %
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	0.23 %		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	-0.07 %		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	0.23 %		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	-0.07 %

Related Entries

Cross References

Resources	Reference
ChEMBL	CHEMBL1738758
DrugBank	DB15110
FDA SRS	67RM91WDHQ
Guide to Pharmacology	7918
PDB	937
PubChem	49792852
SureChEMBL	SCHEMBL1228019
ZINC	ZINC000043196885

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).