BARICITINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H17N7O2S
Molecular Weight	371.417
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCS(=O)(=O)N1CC(CC#N)(C1)N2C=C(C=N2)C3=C4C=CNC4=NC=N3

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	371.417
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase JAK3 27	Inhibitor 8,297	180.0 nM [IC50]
Tyrosine-protein kinase JAK1 38	Inhibitor 8,297	5.9 nM [IC50]
Tyrosine-protein kinase JAK2 55	Inhibitor 8,297	5.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316	Primary		Approved 8,429	OLUMIANT

C_max

Value	Dose	Analyte	Population
34.5 ng/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
29 ng/mL	2 mg 1 times / day steady, oral	BARICITINIB plasma	Homo sapiens
59.2 ng/mL	4 mg 1 times / day steady, oral	BARICITINIB plasma	Homo sapiens
136 ng/mL	10 mg 1 times / day multiple, oral	BARICITINIB plasma	Homo sapiens
48 ng/mL	4 mg 1 times / day multiple, oral	BARICITINIB plasma	Homo sapiens
147 ng/mL	10 mg single, oral	BARICITINIB plasma	Homo sapiens
47.8 ng/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
47.8 ng/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
32.5 ng/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
36.2 ng/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
216 ng × h/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
777 ng*h/mL	10 mg 1 times / day single, oral	BARICITINIB plasma	Homo sapiens
270 ng*h/mL	4 mg 1 times / day single, oral	BARICITINIB plasma	Homo sapiens
771 ng*h/mL	10 mg 1 times / day steady, oral	BARICITINIB plasma	Homo sapiens
265 ng*h/mL	4 mg 1 times / day steady, oral	BARICITINIB plasma	Homo sapiens
216 ng*h/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
273 ng*h/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens
236 ng × h/mL	4 mg single, oral	BARICITINIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.6 h	4 mg single, oral		BARICITINIB plasma	Homo sapiens
7.28 h	4 mg single, oral		BARICITINIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
50%	4 mg single, oral		BARICITINIB plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse 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	unhealthy	Other AEs: Pneumonia, Systemic herpes zoster infection...
2 mg 1 times / day steady, oral Recommended	unhealthy	Disc. AE: Systemic herpes zoster infection, Anemia...
4 mg 1 times / day steady, oral	unhealthy	Disc. AE: Systemic herpes zoster infection, Infestation...

Showing 1 to 5 of 5 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Pneumonia	serious\|grade 5	2 mg 1 times / day steady, oral Recommended	unhealthy
Pulmonary embolism	serious\|grade 5	2 mg 1 times / day steady, oral Recommended	unhealthy
Systemic herpes zoster infection	serious\|grade 5	2 mg 1 times / day steady, oral Recommended	unhealthy
Urinary tract infection	serious\|grade 5	2 mg 1 times / day steady, oral Recommended	unhealthy
Venous thrombosis	serious\|grade 5	2 mg 1 times / day steady, oral Recommended	unhealthy

Showing 1 to 5 of 10 entries

Previous1 2Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587 inducer 781	substrate 1,037 inhibitor 1,767	substrate 1,217 inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT2 145 CYP1A2 1,524 CYP2B6 810 CYP2C8 911 CYP2C19 1,478 P-gp 1,461 OCT1 512 OCT2 647 OAT1 599 OAT3 642 OATP1B1 788 BCRP 699 OATP1B3 706 MATE2 263	CYP1A2 1,054 CYP2B6 664 CYP2C8 693 CYP2C19 991 P-gp 1,537 OAT1 326 OCT1 327 OCT2 355 OATP1B1 406 OAT3 339 BCRP 561 OATP1B3 350 MATE2 96	PXR 9

Drug as perpetrator

Show entries

Target	Modality	Activity
OATP1B1 803	inhibitor 3,277	no
P-gp 1,650	inhibitor 3,277	no
PXR 46	inducer 1,573	no
CYP3A4 1,925	inducer 1,573	unlikely
OAT2 147	inhibitor 3,277	weak [IC50 100 uM]

Showing 1 to 5 of 19 entries

Previous1 2 3 4Next

Drug as victim

Show entries

Target	Modality	Activity
CYP1A2 1,054	substrate 3,367	no
CYP2B6 664	substrate 3,367	no
CYP2C19 991	substrate 3,367	no
CYP2C8 693	substrate 3,367	no
CYP2C9 1,037	substrate 3,367	no

Showing 1 to 5 of 16 entries

Previous1 2 3 4Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
001 Chemical	DY459479	https://www.001chemical.com/chem/1187594-09-7
001 Chemical	DY509857	https://www.001chemical.com/chem/1187595-84-1
AA Blocks	AA003A32	https://www.aablocks.com/goods/Goods/detail?id=AA003A32
Aaron Chemicals	AR003AUU	http://www.aaronchem.com/1187594-09-7
abcr GmbH	AB453191	http://www.abcr.com/shop/en/AB453191

Showing 1 to 5 of 55 entries

Previous1 2 3 4 5…11Next

PubMed

Show entries

Title	Date	PubMed
		252160600
Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.	2010 May 1	20363976

Showing 1 to 2 of 2 entries

Previous1Next

Patents

Sample Use Guides

In Vivo Use Guide

Baricitinib 2 mg administered orally once daily.

Route of Administration: Oral

In Vitro Use Guide

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