FEZOLINETANT

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Search structure


Synonyms	A-2693 A2693 AS-3472693-00 AS3472693-00 ES-256364 ESN-364 ESN364 Esn364 Fezolinetant
Status
Molecule Category	UNKNOWN
UNII	83VNE45KXX


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

Structure


InChI Key	PPSNFPASKFYPMN-SECBINFHSA-N
Smiles	Cc1nsc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)[C@@H]3C)n1
InChI	InChI=1S/C16H15FN6OS/c1-9-13-19-20-14(15-18-10(2)21-25-15)23(13)8-7-22(9)16(24)11-3-5-12(17)6-4-11/h3-6,9H,7-8H2,1-2H3/t9-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C16H15FN6OS
Molecular Weight	358.4
AlogP	2.46
Hydrogen Bond Acceptor	7.0
Hydrogen Bond Donor	0.0
Number of Rotational Bond	2.0
Polar Surface Area	76.8
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	25.0

Bioactivity

Mechanism of Action	Action	Reference
Neurokinin 3 receptor antagonist	ANTAGONIST	Other PubMed


Protein: Neurokinin 3 receptor Description: Neuromedin-K receptor Organism : Homo sapiens P29371 ENSG00000169836

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C19	-	48000	-	-	-
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C9	-	42000	-	-	-
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4	-	90000	-	-	-
Membrane receptor Family A G protein-coupled receptor Peptide receptor (family A GPCR) Short peptide receptor (family A GPCR) Neurokinin receptor	-	20	-	219	-

Assay Description	Organism	Bioactivity	Reference
Binding affinity to human recombinant NK3R by radioligand binding assay	Homo sapiens	25.12 nM
Antagonist activity against human recombinant NK3R expressed in CHO cells by aequorin functional assay	Homo sapiens	19.95 nM
Binding affinity to rat NK3R	Rattus norvegicus	219.0 nM
Binding affinity to monkey NK3R	Macaca mulatta	25.0 nM
Functional Assay: Chinese Hamster Ovary recombinant cells expressing the human NK-3 receptor and a construct that encodes the photoprotein apoaequorin were used for this assay. The antagonist activity of compounds of the invention is measured following pre-incubation (3 minutes) of the compound (at various concentrations) with the cells, followed by addition of the reference agonist (NKA) at a final concentration equivalent to the EC80 (3 nM) and recording of emitted light (FDSS 6000 Hamamatsu) over the subsequent 90-second period. The intensity of the emitted light is integrated using the reader software. Compound antagonist activity is measured based on the concentration-dependent inhibition of the luminescence response to the addition of Neurokinin A.	Homo sapiens	18.0 nM
Competitive Binding Assay: The affinity of compounds of the invention for the human NK-3 receptor was determined by measuring the ability of compounds of the invention to competitively and reversibly displace a well-characterized NK-3 radioligand in a concentration-dependent manner.3H-SB222200 Binding Competition Assay with Human NK-3 ReceptorThe ability of compounds of the invention to inhibit the binding of the NK-3 receptor selective antagonist 3H-SB222200 was assessed by an in vitro radioligand binding assay. Membranes were prepared from Chinese hamster ovary recombinant cells stably expressing the human NK-3 receptor. The membranes were incubated with 5 nM 3H-SB222200 (ARC) in a HEPES 25 mM/NaCl 0.1M/CaCl2 1 mM/MgCl2 5 mM/BSA 0.5%/Saponin 10 μg/ml buffer at pH 7.4 and various concentrations of compounds of the invention. The amount of 3H-SB222200 bound to the receptor was determined after filtration by the quantification of membrane associated radioactivity using the TopCount-NXT reader (Packard).	Homo sapiens	23.0 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL3608680
DrugBank	DB15669
FDA SRS	83VNE45KXX
Guide to Pharmacology	10422
PubChem	117604931
SureChEMBL	SCHEMBL16114810
ZINC	ZINC000218861630

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).