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

Stem definition	Drug id	CAS RN
antivirals RNA polymerase (NS5B) inhibitors	4914	1132935-63-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: dasabuvir sodium monohydrate dasabuvir dasabuvir sodium exviera ABT-333	Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome. In a biochemical assay, dasabuvir inhibited a panel of genotype 1a and 1b NS5B polymerases. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. Molecular weight: 493.58 Formula: C26H27N3O5S CLOGP: 4.07 LIPINSKI: 0 HAC: 8 HDO: 2 TPSA: 104.81 ALOGS: -5.79 ROTB: 5 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

dasabuvir sodium monohydrate
dasabuvir
dasabuvir sodium
exviera
ABT-333

Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome. In a biochemical assay, dasabuvir inhibited a panel of genotype 1a and 1b NS5B polymerases. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor.

Molecular weight: 493.58
Formula: C26H27N3O5S
CLOGP: 4.07
LIPINSKI: 0
HAC: 8
HDO: 2
TPSA: 104.81
ALOGS: -5.79
ROTB: 5

Status: ONP

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

Drug dosage:

Dose	Unit	Route
0.50	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution)	2.13 L/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.01 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.70 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Nov. 20, 2014	EMA	AbbVie Ltd
Dec. 19, 2014	FDA	ABBVIE 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
Jaundice	505.83	22.88	188	7695	28657	46649522
Blood bilirubin increased	365.52	22.88	156	7727	34028	46644151
Hyperbilirubinaemia	355.54	22.88	112	7771	10326	46667853
Hepatic failure	271.92	22.88	126	7757	33290	46644889
Ascites	210.73	22.88	109	7774	36475	46641704
Hepatic encephalopathy	144.62	22.88	57	7826	10100	46668079
Hepatocellular carcinoma	141.99	22.88	41	7842	2798	46675381
Hepatic cirrhosis	133.04	22.88	61	7822	15671	46662508
Asthenia	95.27	22.88	180	7703	310895	46367284
Anaemia	88.35	22.88	156	7727	255623	46422556
Vomiting	81.85	22.88	212	7671	452582	46225597
Nausea	79.91	22.88	275	7608	687179	45991000
Drug ineffective	69.61	22.88	15	7868	677823	46000356
Pruritus	68.84	22.88	136	7747	242216	46435963
Yellow skin	61.37	22.88	20	7863	2044	46676135
Haemoglobin decreased	61.23	22.88	91	7792	128858	46549321
Child-Pugh-Turcotte score increased	60.02	22.88	10	7873	44	46678135
Ocular icterus	57.36	22.88	22	7861	3618	46674561
Renal impairment	56.25	22.88	66	7817	74306	46603873
Bilirubin conjugated increased	56.12	22.88	20	7863	2678	46675501
Chromaturia	49.19	22.88	31	7852	14988	46663191
Fatigue	44.30	22.88	211	7672	608486	46069693
Hepatorenal syndrome	43.74	22.88	15	7868	1793	46676386
Encephalopathy	41.94	22.88	39	7844	33550	46644629
Varices oesophageal	40.73	22.88	16	7867	2803	46675376
Decreased appetite	40.29	22.88	96	7787	193740	46484439
Portal vein thrombosis	39.19	22.88	15	7868	2452	46675727
Oesophageal varices haemorrhage	36.96	22.88	12	7871	1211	46676968
Off label use	35.74	22.88	10	7873	379831	46298348
Upper gastrointestinal haemorrhage	34.56	22.88	26	7857	16712	46661467
Acute hepatic failure	32.94	22.88	24	7859	14697	46663482
Hepatic cancer	32.56	22.88	14	7869	3083	46675096
Blood bilirubin unconjugated increased	30.47	22.88	8	7875	382	46677797
Insomnia	30.35	22.88	78	7805	164846	46513333
Hepatitis C	28.41	22.88	16	7867	6302	46671877
Renal failure	27.71	22.88	60	7823	113534	46564645
Pain	26.49	22.88	25	7858	476923	46201256
Drug hypersensitivity	25.71	22.88	5	7878	243820	46434359

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
Blood bilirubin increased	339.32	21.80	179	8481	36457	29907361
Jaundice	243.21	21.80	138	8522	32348	29911470
Ascites	230.31	21.80	138	8522	35783	29908035
Hepatocellular carcinoma	195.31	21.80	81	8579	9529	29934289
Hepatic cirrhosis	188.16	21.80	92	8568	15907	29927911
Hepatic failure	188.13	21.80	119	8541	33924	29909894
Hyperbilirubinaemia	148.68	21.80	80	8580	16862	29926956
Hepatic encephalopathy	144.42	21.80	74	8586	14118	29929700
Renal impairment	123.06	21.80	136	8524	84048	29859770
Fatigue	95.20	21.80	253	8407	320420	29623398
Yellow skin	64.97	21.80	24	8636	2069	29941749
Anaemia	60.29	21.80	163	8497	207829	29735989
Ocular icterus	59.42	21.80	25	8635	3039	29940779
Hepatitis C	55.52	21.80	39	8621	13166	29930652
Encephalopathy	53.91	21.80	56	8604	32149	29911669
Oesophageal varices haemorrhage	52.91	21.80	23	8637	3028	29940790
Asthenia	51.17	21.80	160	8500	221130	29722688
Blood bilirubin unconjugated increased	50.10	21.80	15	8645	671	29943147
Haemoglobin decreased	49.86	21.80	105	8555	113993	29829825
Portal hypertension	47.66	21.80	23	8637	3850	29939968
Drug interaction	44.91	21.80	143	8517	199425	29744393
Insomnia	44.42	21.80	89	8571	93247	29850571
Distributive shock	42.35	21.80	13	8647	633	29943185
Hepatitis C RNULL increased	39.84	21.80	11	8649	367	29943451
Gastric varices haemorrhage	39.14	21.80	10	8650	246	29943572
Alanine aminotransferase increased	35.52	21.80	71	8589	74205	29869613
Child-Pugh-Turcotte score increased	34.05	21.80	7	8653	62	29943756
Bilirubin conjugated increased	32.69	21.80	17	8643	3334	29940484
Vomiting	29.05	21.80	133	8527	219685	29724133
Nausea	27.70	21.80	163	8497	296794	29647024
Chromaturia	26.65	21.80	26	8634	13839	29929979
Varices oesophageal	26.43	21.80	15	8645	3494	29940324
Hepatic lesion	25.24	21.80	14	8646	3122	29940696
Alpha 1 foetoprotein increased	25.17	21.80	9	8651	706	29943112
Immunosuppressant drug level increased	24.82	21.80	16	8644	4686	29939132
Acute on chronic liver failure	24.34	21.80	6	8654	127	29943691
Death	23.72	21.80	42	8618	357241	29586577
Drug ineffective	23.52	21.80	39	8621	340348	29603470
Irritability	23.35	21.80	31	8629	23019	29920799
Arteriovenous malformation	22.61	21.80	8	8652	609	29943209
Hepatorenal syndrome	22.40	21.80	12	8648	2499	29941319
Headache	22.36	21.80	108	8552	182198	29761620

Pharmacologic Action:

Source	Code	Description
ATC	J05AP09	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
ATC	J05AP52	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA EPC	N0000191257	Hepatitis C Virus Non-Nucleoside NS5B Palm Polymerase Inhibitor
FDA MoA	N0000191258	RNULL Replicase Inhibitors
FDA MoA	N0000191272	UGT1A1 Inhibitors
CHEBI has role	CHEBI:36044	anti-virus drug
CHEBI has role	CHEBI:85180	nonstructural protein 5b inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.38	acidic
pKa2	9.01	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

None

External reference:

ID	Source
D10553	KEGG_DRUG
1456607-55-8	SECONDARY_CAS_RN
4034028	VANDF
C3850285	UMLSCUI
CHEBI:85182	CHEBI
CHEMBL3137312	ChEMBL_ID
56640146	PUBCHEM_CID
CHEMBL3544985	ChEMBL_ID
DB09183	DRUGBANK_ID
C588260	MESH_SUPPLEMENTAL_RECORD_UI
11270	IUPHAR_LIGAND_ID
9741	INN_ID
DE54EQW8T1	UNII
1597381	RXNORM
30778	MMSL
31899	MMSL
d08322	MMSL
015829	NDDF
015830	NDDF
714104000	SNOMEDCT_US
714105004	SNOMEDCT_US
716018007	SNOMEDCT_US
725851005	SNOMEDCT_US

Pharmaceutical products:

None