U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H19F3N6O
Molecular Weight 380.3682
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of UPADACITINIB

SMILES

CC[C@]1([H])CN(C[C@]1([H])c2cnc3cnc4c(cc[nH]4)n23)C(=NCC(F)(F)F)O

InChI

InChIKey=WYQFJHHDOKWSHR-MNOVXSKESA-N
InChI=1S/C17H19F3N6O/c1-2-10-7-25(16(27)24-9-17(18,19)20)8-11(10)13-5-22-14-6-23-15-12(26(13)14)3-4-21-15/h3-6,10-11,21H,2,7-9H2,1H3,(H,24,27)/t10-,11+/m1/s1

HIDE SMILES / InChI
Upadacitinib (ABT-494) is a Janus kinase 1 (JAK1) inhibitor currently being developed by AbbVie for the treatment of rheumatoid arthritis (RA), Crohn’s disease, ulcerative colitis, atopic dermatitis, and psoriatic arthritis. It is also being investigated as a potential treatment for people with active ankylosing spondylitis (AS). Currently, upadacitinib is being evaluatedin six global phase III studies in RA and twophase III studies in psoriatic arthritis (PsA), inaddition to phase II studies in Crohn’s disease and atopicdermatitis and a combined phase II/III study inulcerative colitis. Upadacitinib is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
43 nM [IC50]
200 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RINVOQ

Approved Use

RINVOQ is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.

Launch Date

1565827200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
63.7 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UPADACITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
491 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UPADACITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
18.1 h
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UPADACITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
48%
UPADACITINIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Other AEs: Anemia, Neutropenia...
Other AEs:
Anemia (2.4%)
Neutropenia (4.8%)
Atopic dermatitis (9.5%)
Acne (14%)
Headache (9.5%)
Nasopharyngitis (7.1%)
CPK increased (9.5%)
Nausea (7.1%)
Sources:
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Other AEs: Adverse event...
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Disc. AE: Anemia, Vertigo...
AEs leading to
discontinuation/dose reduction:
Anemia (2 patients)
Vertigo (2 patients)
Bronchitis (2 patients)
ALT increased (2 patients)
Aspartate aminotransferase increased (3 patients)
Increased serum creatinine (2 patients)
Headache (2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Acne 14%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Anemia 2.4%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Neutropenia 4.8%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Nasopharyngitis 7.1%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Nausea 7.1%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Atopic dermatitis 9.5%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
CPK increased 9.5%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Headache 9.5%
30 mg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 39.9 years (range: 18-75 years)
Health Status: unhealthy
Age Group: 39.9 years (range: 18-75 years)
Sex: M+F
Sources:
Adverse event grade 5
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
ALT increased 2 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Anemia 2 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Bronchitis 2 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Headache 2 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Increased serum creatinine 2 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Vertigo 2 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Aspartate aminotransferase increased 3 patients
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minor
no [IC50 181 uM]
weak (co-administration study)
Comment: Clinically no meaningful effect on midazolam (sensitive CYP3A4 substrate), Coadministration of Upadacitinib (30 mg QD extended-release) decreased Cmax by 16% and AUCinf by 26%., IC50=181 mcM (midazolam) and 212 mcM (teststerone), Upadacitinib caused no detectable time-dependent inhibition of any isoform tested upto a concentration of 50 µM.
Page: 11, 18, 19, 23, 77-85
no [IC50 40.3 uM]
no (co-administration study)
Comment: Clinically no meaningful effect on S-warffarin (sensitive CYP2C9 substrate), Coadministration of Upadacitinib (30 mg QD extended-release) increased Cmax by 7% and AUCinf by 11%., Upadacitinib caused no detectable time-dependent inhibition of any isoform tested up to a concentration of 50 µM.
Page: 11, 18, 19, 23, 77-85
no [IC50 >250 uM]
no (co-administration study)
Comment: Clinically no meaningful effect on omeprazole (sensitive CYP2C19 substrate), Coadministration of Upadacitinib (30 mg QD extended-release) increased AUCinf Ratio (5-OH OME to OME metabolic ratio) by 9%., Upadacitinib caused no detectable time-dependent inhibition of any isoform tested up to a concentration of 50 µM.
Page: 11, 18, 19, 23, 77-85
no [IC50 >250 uM]
no (co-administration study)
Comment: Clinically no meaningful effect on dextromethorphan (sensitive CYP2D6 substrate), Coadministration of Upadacitinib (30 mg QD extended-release) increased Cmax by 9% and AUCinf by 7%., Upadacitinib caused no detectable time-dependent inhibition of any isoform tested up to a concentration of 50 µM.
Page: 11, 18, 19, 23, 77-85
no [IC50 >250 uM]
weak (co-administration study)
Comment: Clinically no meaningful effect on caffeine (sensitive CYP1A2 substrate), Coadministration of Upadacitinib (30 mg QD extended-release) increased Cmax by 13% and AUCinf by 22%., Upadacitinib caused no detectable time-dependent inhibition of any isoform tested up to a concentration of 50 µM.
Page: 11, 18, 19, 23, 77-85
no [IC50 >250 uM]
weak (co-administration study)
Comment: Clinically no meaningful effect on bupropion (CYP2B6 substrate), Coadministration of Upadacitinib (30 mg QD extended-release) decreased Cmax by 13.2% and AUCinf by 7.6%., Upadacitinib caused no detectable time-dependent inhibition of any isoform tested up to a concentration of 50 µM.
Page: 11, 18, 19, 23, 87-89
unlikely [IC50 10 uM]
unlikely [IC50 10 uM]
unlikely [IC50 120 uM]
unlikely [IC50 220 uM]
unlikely [IC50 35 uM]
unlikely [IC50 48 uM]
unlikely [IC50 510 uM]
unlikely [IC50 >30 uM]
unlikely [IC50 >30 uM]
unlikely [IC50 >30 uM]
unlikely [IC50 >30 uM]
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: When upadacitinib was co-administered with ketoconazole (a strong CYP3A4 inhibitor, 400 mg QD x 6 days), upadacitinib exposure increased by 75% for AUC0-inf and 70% for Cmax. Upadacitinib should be used with caution if patients receive chronic treatment with strong CYP3A4 inhibitors. When upadacitinib was co-administered with rifampin (a strong CYP3A4 inducer, 600 mg QD x 9 days), upadacitinib exposure decreased by 61% for AUC0-inf and 51% for Cmax. Upadacitinib is not recommended to be co-administered with strong CYP3A4 inducers.
Page: 5, 10, 17, 18, 23, 70-72
minor
minor
no
no
no
no (co-administration study)
Comment: OATP1B inhibitor (rifampin, 600 mg SD) do not have clinically meaningful effect on upadacitinib PK (increased Cmax by 14% and AUCinf by 7%).
Page: 11, 18, 23
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate.
2016 Dec
A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy.
2016 Dec
Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis.
2016 Dec
Population Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I and II Clinical Trials.
2018 Aug
Patents

Sample Use Guides

The recommended dose of RINVOQ (Upadacitinib) is 15 mg once daily.
Route of Administration: Oral
Upadacitinib is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM.
Name Type Language
UPADACITINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
ABBV-599 COMPONENT UPADACITINIB
Common Name English
UPADACITINIB [ORANGE BOOK]
Common Name English
(3S,4R)-3-ETHYL-4-(3H-IMIDAZO(1,2-A)PYRROLO(2,3-E)PYRAZIN- 8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE TYROSINE KINASE INHIBITOR
Common Name English
UPADACITINIB [USAN]
Common Name English
(3S,4R)-3-ETHYL-4-(3H-IMIDAZO(1,2-A)PYRROLO(2,3-E)PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)-1-PYRROLIDINECARBOXAMIDE
Systematic Name English
ABT-494
Code English
UPADACITINIB COMPONENT OF ABBV-599
Common Name English
1-PYRROLIDINECARBOXAMIDE, 3-ETHYL-4-(3H-IMIDAZO(1,2-A)PYRROLO(2,3-E)PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)-, (3S,4R)-
Systematic Name English
UPADACITINIB [WHO-DD]
Common Name English
UPADACITINIB ANHYDROUS
Common Name English
UPADACITINIB [INN]
Common Name English
REL-(-)-(3S,4R)-3-ETHYL-4-(3H-IMIDAZO(1,2-A)PYRROLO(2,3-E)PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
FDA ORPHAN DRUG 522916
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
FDA ORPHAN DRUG 524116
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
FDA ORPHAN DRUG 575517
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
Code System Code Type Description
RXCUI
2196092
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
INN
10209
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
DRUG CENTRAL
5346
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
FDA UNII
4RA0KN46E0
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
PUBCHEM
58557659
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
DRUG BANK
DB15091
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
NCI_THESAURUS
C152802
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
CAS
1310726-60-3
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY
LACTMED
Upadacitinib
Created by admin on Sat Jun 26 00:26:30 UTC 2021 , Edited by admin on Sat Jun 26 00:26:30 UTC 2021
PRIMARY