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

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	5202	1187594-09-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: baricitinib LY3009104 INCB028050 olumiant	Baricitinib is a selective and reversible inhibitor of Janus kinase (JAK)1 and JAK2. Janus kinases (JAKs) are enzymes that transduce intracellular signals from cell surface receptors for a number of cytokines and growth factors involved in haematopoiesis, inflammation and immune function. Within the intracellular signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which activate gene expression within the cell. Baricitinib modulates these signalling pathways by partially inhibiting JAK1 and JAK2 enzymatic activity, thereby reducing the phosphorylation and activation of STATs. FDA issued an Emergency use authorization (EUA) on November 19, 2020 that permits use of baricitinib in combination with remdesivir for treatment of suspected or laboratory-confirmed COVID-19 in hospitalized patients ≥2 years of age requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Molecular weight: 371.42 Formula: C16H17N7O2S CLOGP: 0.41 LIPINSKI: 0 HAC: 9 HDO: 1 TPSA: 120.56 ALOGS: -3.02 ROTB: 4 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

baricitinib
LY3009104
INCB028050
olumiant

Baricitinib is a selective and reversible inhibitor of Janus kinase (JAK)1 and JAK2. Janus kinases (JAKs) are enzymes that transduce intracellular signals from cell surface receptors for a number of cytokines and growth factors involved in haematopoiesis, inflammation and immune function. Within the intracellular signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which activate gene expression within the cell. Baricitinib modulates these signalling pathways by partially inhibiting JAK1 and JAK2 enzymatic activity, thereby reducing the phosphorylation and activation of STATs. FDA issued an Emergency use authorization (EUA) on November 19, 2020 that permits use of baricitinib in combination with remdesivir for treatment of suspected or laboratory-confirmed COVID-19 in hospitalized patients ≥2 years of age requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Molecular weight: 371.42
Formula: C16H17N7O2S
CLOGP: 0.41
LIPINSKI: 0
HAC: 9
HDO: 1
TPSA: 120.56
ALOGS: -3.02
ROTB: 4

Status: ONP

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

Drug dosage:

Dose	Unit	Route
4	mg	O

ADMET properties:

None

Approvals:

Date	Agency	Company
May 31, 2018	FDA	ELI LILLY AND CO
July 3, 2017	PMDA	Eli Lilly Japan KK
Feb. 13, 2017	EMA	Eli Lilly Nederland B.V.

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
Therapy interrupted	71.08	25.33	23	1682	10768	46673589
Therapy cessation	70.66	25.33	29	1676	26600	46657757
COVID-19	66.03	25.33	25	1680	18550	46665807
Tooth dislocation	45.66	25.33	6	1699	24	46684333
Herpes zoster	35.41	25.33	25	1680	67847	46616510
Pneumonia haemophilus	33.87	25.33	7	1698	554	46683803
Ovarian adenoma	32.62	25.33	6	1699	258	46684099
Tubular breast carcinoma	27.11	25.33	4	1701	42	46684315
COVID-19 pneumonia	25.76	25.33	8	1697	3267	46681090

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

Pharmacologic Action:

Source	Code	Description
ATC	L04AA37	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Selective immunosuppressants
FDA MoA	N0000190857	Janus Kinase Inhibitors
FDA EPC	N0000190858	Janus Kinase Inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Rheumatoid arthritis	indication	69896004	DOID:7148
Coronavirus infection	off-label use	186747009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	6.49	acidic
pKa2	4.6	Basic
pKa3	1.9	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
2MG	OLUMIANT	ELI LILLY AND CO	N207924	May 31, 2018	RX	TABLET	ORAL	May 31, 2023	NEW CHEMICAL ENTITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Tyrosine-protein kinase JAK1	Kinase	P23458	JAK1_HUMAN	INHIBITOR	IC50	8.23	SCIENTIFIC LITERATURE	DRUG LABEL
Tyrosine-protein kinase JAK2	Kinase	O60674	JAK2_HUMAN	INHIBITOR	IC50	8.24	SCIENTIFIC LITERATURE	DRUG LABEL
Non-receptor tyrosine-protein kinase TYK2	Kinase	P29597	TYK2_HUMAN	INHIBITOR	IC50	7.28	SCIENTIFIC LITERATURE
Tyrosine-protein kinase JAK3	Kinase	P52333	JAK3_HUMAN		IC50	6.10	CHEMBL

External reference:

ID	Source
ISP4442I3Y	UNII
4037600	VANDF
C4044947	UMLSCUI
3JW	PDB_CHEM_ID
CHEMBL2105759	ChEMBL_ID
DB11817	DRUGBANK_ID
D10308	KEGG_DRUG
44205240	PUBCHEM_CID
9570	INN_ID
C000596027	MESH_SUPPLEMENTAL_RECORD_UI
7792	IUPHAR_LIGAND_ID
2047232	RXNORM
256448	MMSL
32650	MMSL
d08568	MMSL
017220	NDDF
726518002	SNOMEDCT_US
763701005	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Olumiant	HUMAN PRESCRIPTION DRUG LABEL	1	0002-4182	TABLET, FILM COATED	2 mg	ORAL	NDA	33 sections
Olumiant	HUMAN PRESCRIPTION DRUG LABEL	1	0002-4732	TABLET, FILM COATED	1 mg	ORAL	NDA	33 sections