IVACAFTOR

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Search structure


Trade Names	KALYDECO
Synonyms	Ivacaftor Kalydeco VX-770
Status
Molecule Category	Free-form
ATC	R07AX02
UNII	1Y740ILL1Z
EPA CompTox	DTXSID00236281


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

Structure


InChI Key	PURKAOJPTOLRMP-UHFFFAOYSA-N
Smiles	CC(C)(C)c1cc(C(C)(C)C)c(NC(=O)c2c[nH]c3ccccc3c2=O)cc1O
InChI	InChI=1S/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C24H28N2O3
Molecular Weight	392.5
AlogP	5.08
Hydrogen Bond Acceptor	3.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	2.0
Polar Surface Area	82.19
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	29.0

Bioactivity

Mechanism of Action	Action	Reference
Cystic fibrosis transmembrane conductance regulator positive modulator	POSITIVE MODULATOR	DailyMed


Protein: Cystic fibrosis transmembrane conductance regulator Description: Cystic fibrosis transmembrane conductance regulator Organism : Homo sapiens P13569 ENSG00000001626

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Ion channel Other ion channel Chloride channel Cystic fibrosis transmembrane conductance regulator	3-1300	-	-	-	-

Assay Description	Organism	Bioactivity	Reference
Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay	Homo sapiens	3.0 nM
Potentiation of human CFTR F508del mutant in human bronchial epithelial cells by Ussing chambers recording technique	Homo sapiens	236.0 nM
Potentiation of human CFTR F508del/G551D mutant in human bronchial epithelial cells by Ussing chambers recording technique	Homo sapiens	22.0 nM
Corrector activity at CFTR mutant (unknown origin) by phenotypic screening assay	Homo sapiens	3.0 nM
Corrector activity at human bronchial epithelium CFTR F508del and G551D mutant assessed as increase in channel gating	Homo sapiens	236.0 nM
Inhibition of TGF-beta1-induced total collagen accumulation in rat NRK-49F cells at 10 uM	Rattus norvegicus	64.7 %
Inhibition of LPS-induced TNFalpha production in mouse RAW264.7 cells 10 uM	Mus musculus	63.2 %
Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	Homo sapiens	126.0 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	37.01 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	15.93 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	4.87 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	0.8778 %
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	0.74 %		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	3.21 %		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	-0.42 %		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	0.74 %		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	-0.42 %		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	3.21 %
Potentiator activity at CFTR F508del mutant (unknown origin) expressed in CFBE41o cells assessed as increase in forskolin induced transepithelial short circuit current by Ussing chamber assay	Homo sapiens	11.7 nM
Potentiation of CFTR F508del mutant (unknown origin) expressed in FRT cells assessed as chloride transport by measuring membrane potential in presence of forskolin	Homo sapiens	49.0 nM
Potentiation of wild-type CFTR (unknown origin) expressed in FRT cells assessed as chloride transport by measuring membrane potential in presence of forskolin	Homo sapiens	70.0 nM
Potentiation of CFTR G551D mutant (unknown origin) expressed in FRT cells assessed as chloride transport by measuring membrane potential in presence of forskolin	Homo sapiens	131.0 nM
Potentiation of CFTR F508 deletion mutant (unknown origin) expressed in HBE cells assessed as change in short circuit current in presence of forskolin and amiloride	Homo sapiens	68.0 nM
Potentiation of wild type CFTR (unknown origin) expressed in HBE cells assessed as change in short circuit current in presence of forskolin and amiloride	Homo sapiens	34.0 nM

Related Entries

Cross References

Resources	Reference
ChEBI	66901
ChEMBL	CHEMBL2010601
DrugBank	DB08820
DrugCentral	4228
FDA SRS	1Y740ILL1Z
Human Metabolome Database	HMDB0015705
Guide to Pharmacology	4342
PDB	VX7
PharmGKB	PA165950341
PubChem	16220172
SureChEMBL	SCHEMBL351373
ZINC	ZINC000052509463

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).