elexacaftor Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
cystic fibrosis transmembrane regulator (CFTR) protein modulators	5372	2216712-66-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: elexacaftor	Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport. Molecular weight: 597.66 Formula: C26H34F3N7O4S CLOGP: 4.43 LIPINSKI: 2 HAC: 11 HDO: 1 TPSA: 124.24 ALOGS: -4.49 ROTB: 8 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

elexacaftor

Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport.

Molecular weight: 597.66
Formula: C26H34F3N7O4S
CLOGP: 4.43
LIPINSKI: 2
HAC: 11
HDO: 1
TPSA: 124.24
ALOGS: -4.49
ROTB: 8

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Aug. 21, 2020	EMA	Vertex Pharmaceuticals (Ireland) Limited
Oct. 10, 2019	FDA	VERTEX PHARMS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Infective pulmonary exacerbation of cystic fibrosis	464.51	40.72	114	3042	10693	46672213
Productive cough	218.66	40.72	93	3063	50622	46632284
Headache	139.10	40.72	165	2991	478187	46204719
Cough	116.19	40.72	107	3049	230142	46452764
Abdominal pain upper	111.34	40.72	86	3070	145219	46537687
Hospitalisation	84.97	40.72	53	3103	63332	46619574
Influenza	84.31	40.72	60	3096	89210	46593696
Rash	71.71	40.72	103	3053	356409	46326497
Haemoptysis	71.39	40.72	35	3121	26154	46656752
Cystic fibrosis	59.33	40.72	18	3138	3670	46679236
Sputum increased	57.74	40.72	15	3141	1741	46681165
Weight increased	54.35	40.72	61	3095	164412	46518494
Paranasal sinus hypersecretion	53.00	40.72	16	3140	3208	46679698
Exposure during pregnancy	46.13	40.72	46	3110	108166	46574740
Distal intestinal obstruction syndrome	43.38	40.72	9	3147	388	46682518

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Infective pulmonary exacerbation of cystic fibrosis	332.51	51.27	84	2034	8488	29941872
Productive cough	259.01	51.27	92	2026	29861	29920499
Headache	143.20	51.27	111	2007	182195	29768165
Abdominal pain upper	131.57	51.27	71	2047	62480	29887880
Cough	103.69	51.27	79	2039	125563	29824797
Influenza	73.97	51.27	43	2075	43355	29907005
Sputum increased	70.78	51.27	18	2100	1839	29948521
Testicular pain	68.19	51.27	19	2099	2753	29947607
Weight increased	54.80	51.27	44	2074	74869	29875491
Paranasal sinus hypersecretion	52.50	51.27	12	2106	780	29949580

Pharmacologic Action:

Source	Code	Description
ATC	R07AX32	RESPIRATORY SYSTEM OTHER RESPIRATORY SYSTEM PRODUCTS OTHER RESPIRATORY SYSTEM PRODUCTS Other respiratory system products
MeSH PA	D065101	Chloride Channel Agonists
MeSH PA	D049990	Membrane Transport Modulators

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Cystic fibrosis	indication	190905008	DOID:1485

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.64	acidic
pKa2	1.88	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
100MG,75MG,50MG;N/A,150MG,N/A	TRIKAFTA (COPACKAGED)	VERTEX PHARMS INC	N212273	Oct. 21, 2019	RX	TABLET, TABLET	ORAL	Feb. 12, 2023	NEW CHEMICAL ENTITY
100MG,75MG,50MG;N/A,150MG,N/A	TRIKAFTA (COPACKAGED)	VERTEX PHARMS INC	N212273	Oct. 21, 2019	RX	TABLET, TABLET	ORAL	Oct. 21, 2024	NEW CHEMICAL ENTITY
100MG,75MG,50MG;N/A,150MG,N/A	TRIKAFTA (COPACKAGED)	VERTEX PHARMS INC	N212273	Oct. 21, 2019	RX	TABLET, TABLET	ORAL	Oct. 21, 2026	INDICATED FOR THE TREATMENT OF CYSTIC FIBROSIS (CF) IN PATIENTS AGED 12 YEARS AND OLDER WHO HAVE AT LEAST ONE F508DEL MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE
100MG,75MG,50MG;N/A,150MG,N/A	TRIKAFTA (COPACKAGED)	VERTEX PHARMS INC	N212273	Oct. 21, 2019	RX	TABLET, TABLET	ORAL	Dec. 21, 2027	TREATMENT OF CYSTIC FIBROSIS (CF) IN PATIENTS AGED 12 YEARS AND OLDER WHO HAVE A MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE THAT IS RESPONSIVE BASED ON IN VITRO DATA

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Cystic fibrosis transmembrane conductance regulator	Ion channel	P13569	CFTR_HUMAN					UNKNOWN	DRUG LABEL

External reference:

ID	Source
4038884	VANDF
C5139717	UMLSCUI
CHEMBL4298128	ChEMBL_ID
DB15444	DRUGBANK_ID
D11700	KEGG_DRUG
C000629074	MESH_SUPPLEMENTAL_RECORD_UI
134587348	PUBCHEM_CID
10552	IUPHAR_LIGAND_ID
11180	INN_ID
RRN67GMB0V	UNII
2256951	RXNORM
37631	MMSL
d09420	MMSL
018170	NDDF
827070004	SNOMEDCT_US

Pharmaceutical products:

None