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

Details

Stereochemistry ACHIRAL
Molecular Formula C16H17N7O2S
Molecular Weight 371.4186
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BARICITINIB

SMILES

CCS(=O)(=O)N1CC(CC#N)(C1)n2cc(cn2)-c3c-4ccnc4[nH]cn3

InChI

InChIKey=XUZMWHLSFXCVMG-UHFFFAOYSA-N
InChI=1S/C16H17N7O2S/c1-2-26(24,25)22-9-16(10-22,4-5-17)23-8-12(7-21-23)14-13-3-6-18-15(13)20-11-19-14/h3,6-8,11H,2,4,9-10H2,1H3,(H,18,19,20)

HIDE SMILES / InChI

Molecular Formula C16H17N7O2S
Molecular Weight 371.4186
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Baricitinib (trade name Olumiant) is an investigational drug for rheumatoid arthritis (RA), being developed by Incyte and Eli Lilly. Baricitinib is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays. In February 2017 Baricitinib was approved for use in the European Union as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate. On 31 May 2018 FDA approved Barictinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
180 nM [IC50]
5.90000000000000036 nM [IC50]
5.70000000000000018 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
OLUMIANT

Approved Use

OLUMIANT is a Janus kinase (JAK) inhibitor indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Launch Date

1275177600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
36.2 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BARICITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
47.8 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status: Fasted
32.5 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status: High fat meal
136 ng/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: oral
experiment type: multiple
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
147 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
29 ng/mL
2 mg 1 times / day steady, oral
dose: 2 mg
route of administration: oral
experiment type: steady
co-administered:
BARICITINIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
47.8 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
48 ng/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: oral
experiment type: multiple
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
59.2 ng/mL
4 mg 1 times / day steady, oral
dose: 4 mg
route of administration: oral
experiment type: steady
co-administered:
BARICITINIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
236 ng × h/mL
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BARICITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
265 ng*h/mL
4 mg 1 times / day steady, oral
dose: 4 mg
route of administration: oral
experiment type: steady
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
771 ng*h/mL
10 mg 1 times / day steady, oral
dose: 10 mg
route of administration: oral
experiment type: steady
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
216 ng*h/mL
4 mg single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status: Fasted
273 ng*h/mL
4 mg single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status: High fat meal
270 ng*h/mL
4 mg 1 times / day single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
777 ng*h/mL
10 mg 1 times / day single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
BARICITINIB plasma
Homo sapiens
population: healthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.28 h
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BARICITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BARICITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, oral
Highest studied dose
healthy, 30.6 years (ramge: 18–55 years)
40 mg single, oral
Highest studied dose
healthy
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Other AEs: Pneumonia, Systemic herpes zoster infection...
Other AEs:
Pneumonia (serious|grade 5)
Systemic herpes zoster infection (serious|grade 5)
Urinary tract infection (serious|grade 5)
Venous thrombosis (serious|grade 5)
Pulmonary embolism (serious|grade 5)
Sources:
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Systemic herpes zoster infection, Anemia...
AEs leading to
discontinuation/dose reduction:
Systemic herpes zoster infection (1%)
Anemia (0.6%)
Sources:
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Systemic herpes zoster infection, Infestation...
AEs leading to
discontinuation/dose reduction:
Systemic herpes zoster infection (1%)
Infestation (1.6%)
Alanine aminotransferase increase (0.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Pneumonia serious|grade 5
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Pulmonary embolism serious|grade 5
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Systemic herpes zoster infection serious|grade 5
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Urinary tract infection serious|grade 5
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Venous thrombosis serious|grade 5
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Anemia 0.6%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Systemic herpes zoster infection 1%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy
Alanine aminotransferase increase 0.2%
Disc. AE
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy
Systemic herpes zoster infection 1%
Disc. AE
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy
Infestation 1.6%
Disc. AE
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
unlikely
weak [IC50 100 uM]
weak [IC50 >25 uM]
weak [IC50 >25 uM]
weak [IC50 >25 uM]
weak [IC50 >25 uM]
weak [IC50 >25 uM]
weak [IC50 >25 uM]
weak [IC50 >25 uM]
yes [IC50 11.6 uM]
yes [IC50 13.7 uM]
yes (co-administration study)
Comment: transport of metformin was inhibited by LY3009104
Page: 60
yes [IC50 49.4 uM]
yes [IC50 50 uM]
yes [IC50 6.9 uM]
yes [IC50 8.4 uM]
yes [IC50 >100 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes (co-administration study)
Comment: the bii-directional transport ratio of LY3009104 reduced in the presence of BCRP inhibitors Kol43, FTC, and GF120918
Page: 59
yes
yes (co-administration study)
Comment: uptake was inhibited by probenecid; probenecid increased baricitinib AUC by 2-fold
Page: 41, 59
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.
2010 May 1
Patents

Sample Use Guides

Baricitinib 2 mg administered orally once daily.
Route of Administration: Oral
Baricitinib inhibits IL-6–stimulated phosphorylation of the canonical substrate STAT3 (pSTAT3) and subsequent production of the chemokine MCP-1 with IC50 values of 44 nM and 40 nM, respectively, in PBMCs. Baricitinib also inhibits pSTAT3 stimulated by IL-23 with IC50 of 20 nM in isolated naive T-cells
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:52:47 UTC 2021
Edited
by admin
on Fri Jun 25 23:52:47 UTC 2021
Record UNII
ISP4442I3Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BARICITINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
BARICITINIB [INN]
Common Name English
BARICITINIB [ORANGE BOOK]
Common Name English
BARICITINIB [WHO-DD]
Common Name English
LY3009104
Code English
BARICITINIB [USAN]
Common Name English
3-AZETIDINEACETONITRILE, 1-(ETHYLSULFONYL)-3-(4-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)-1H-PYRAZOL-1-YL)-
Systematic Name English
BARICITINIB [JAN]
Common Name English
BARICITINIB [EMA EPAR]
Common Name English
BARICITINIB [MI]
Common Name English
INCB028050
Code English
INCB-028050
Code English
LY-3009104
Code English
OLUMIANT
Brand Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS OLUMIANT (AUTHORIZED: ARTHRITIS, RHEUMATOID)
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
NCI_THESAURUS C1967
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
WHO-ATC L04AA37
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
NDF-RT N0000190858
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
FDA ORPHAN DRUG 610017
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
Code System Code Type Description
PUBCHEM
44205240
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
FDA UNII
ISP4442I3Y
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
DRUG BANK
DB11817
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
DRUG CENTRAL
5202
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
NCI_THESAURUS
C127012
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
EVMPD
SUB180983
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
ChEMBL
CHEMBL2105759
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
CAS
1187594-09-7
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
MERCK INDEX
M12076
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
RXCUI
2047232
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
LACTMED
Baricitinib
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
INN
9570
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
EPA CompTox
1187594-09-7
Created by admin on Fri Jun 25 23:52:47 UTC 2021 , Edited by admin on Fri Jun 25 23:52:47 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
URINE
TARGET->WEAK INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
Only 4 minor oxidative metabolites were identified (3 in urine; 1 in faeces) constituting approximately 5 % and 1 % of the dose, respectively.
TRANSPORTER -> SUBSTRATE
Coadministration of baricitinib with ciclosporin (Pgp/BCRP inhibitor) resulted in no clinically meaningful effects on baricitinib exposure.
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
Coadministration of baricitinib with ciclosporin (Pgp/BCRP inhibitor) resulted in no clinically meaningful effects on baricitinib exposure.
EXCRETED UNCHANGED
FECAL
TRANSPORTER -> SUBSTRATE
A clinical pharmacology study, dosing of probenecid (an OAT3 inhibitor with strong inhibition potential) resulted in approximately a 2-fold increase in AUC(0-?) with no change in tmax or Cmax of baricitinib.
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC