GEFAPIXANT

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Search structure


Synonyms	AF-219 Af-219 Gefapixant R-1646 R1646 RG-1646 RG1646 RO-4926219 RO4926219
Status
Molecule Category	UNKNOWN
UNII	6K6L7E3F1L


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

Structure


InChI Key	HLWURFKMDLAKOD-UHFFFAOYSA-N
Smiles	COc1cc(C(C)C)c(Oc2cnc(N)nc2N)cc1S(N)(=O)=O
InChI	InChI=1S/C14H19N5O4S/c1-7(2)8-4-10(22-3)12(24(17,20)21)5-9(8)23-11-6-18-14(16)19-13(11)15/h4-7H,1-3H3,(H2,17,20,21)(H4,15,16,18,19)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C14H19N5O4S
Molecular Weight	353.4
AlogP	1.21
Hydrogen Bond Acceptor	8.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	5.0
Polar Surface Area	156.44
Molecular species	NEUTRAL
Aromatic Rings	2.0
Heavy Atoms	24.0

Bioactivity

Mechanism of Action	Action	Reference
P2X purinoceptor 3 antagonist	ANTAGONIST	PubMed Other

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Ion channel Ligand-gated ion channel P2X receptor	-	45	-	-	-

Assay Description	Organism	Bioactivity	Reference
Antagonist activity against rat P2X3 receptor expressed in CHOK1 cells assessed as inhibition of alpha,beta-meATP-induced calcium response incubated for 20 mins by Fluo-3AM dye based FLIPR assay	Rattus norvegicus	70.79 nM
Antagonist activity against human P2X2/3 receptor expressed in CHOK1 cells assessed as inhibition of alpha,beta-meATP-induced calcium response incubated for 20 mins by Fluo-3AM dye based FLIPR assay	Homo sapiens	89.13 nM
Anti-tussive activity in idiopathic/treatment-resistant chronic cough patient assessed as reduction in daytime cough per hour at 600 mg BID measured after 2 weeks during double-blind randomized placebo-controlled crossover trial	Homo sapiens	75.0 %
Anti-tussive activity in patient with refractory chronic cough assessed as reduction in objective daytime cough counts at 600 mg BID measured after 2 weeks during double-blind randomized placebo-controlled crossover trial	Homo sapiens	75.0 %
Antagonist activity at human recombinant P2X3 receptor expressed in HEK293-Tet-on cells assessed as alpha,beta-methylene-ATP-stimulated Ca2+ influx by Fluo-4 assay	Homo sapiens	45.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	1.32 %
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	-0.12 %		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	-0.12 %

Cross References

Resources	Reference
ChEMBL	CHEMBL3716057
DrugBank	DB15097
FDA SRS	6K6L7E3F1L
Guide to Pharmacology	9540
PDB	AF9
PubChem	24764487
SureChEMBL	SCHEMBL1493905
ZINC	ZINC000116342482

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).