General
Preferred name
BARICITINIB
Synonyms
INCB-28050, LY-3009104, INCB-028050 ()
LY3009104 ()
Baricitinib phosphate ()
INCB028050 ()
INCB-028050 phosphate ()
LY-3009104 phosphate ()
Baricitinib?Phosphate ()
Baricitinib (LY3009104) ()
3JW ()
Baricitinib (phosphate) ()
BARICITINIB PHOSPHATE SALT ()
INCB-028050 ()
INCB-28050 ()
LY-3009104 ()
OLUMIANT ()
LY3009104 (phosphate) ()
INCB028050 (phosphate) ()
Baricitinib (INCB028050) ()
INCB-028050 phosphate, LY-3009104 phosphate ()
P&D ID
PD010550
CAS
1187594-09-7
1187595-84-1
Tags
available
probe
drug
Approved by
PMDA
EMA
FDA
First approval
2018
2017
Drug Status
investigational
approved
Drug indication
Asthma
Psoriatic arthritis
Rheumatoid arthritis
Coronavirus Disease 2019 (COVID-19)
Systemic lupus erythematosus
Atopic dermatitis
Max Phase
Phase 4
Probe info
Probe type
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
42
No orthogonal probes found
Similar probes
1
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Baricitinib is a JAK1 and 2 selective inhibitor. The compound is orally bioavailable.
SARS-CoV-2 and COVID-19: The powerful anti-inflammatory activity of baricitinib (and potentially other approved JAK inhibitors such as , and ) was suggested as potential therapeutic option to combat the immunopathological effects of SARS-CoV-2 infection in patients with severe COVID-19. A number of small-medium sized clinical studies have examined the effect of short-term baricitinib (or other JAK inhibitors) treatment in hospitalised patients with confirmed COVID-19. Such short term use of this drug during the course of SARS-CoV-2 infection (7-14 days) is not anticipated to cause serious side-effects. In March 2022, data reported from the largest of the baricitinib studies (part of the University of Oxford-led RECOVERY trial) indicated that it provided clinical benefit in hospitalised COVID-19 patients, including in those already receiving other standard care immunomodulatory treatments (e.g. , ) or the antiviral drug . This made baricitinib the 4th effective COVID-19 therapy to be identified by the RECOVERY trial.
Through the application of proprietary artificial intelligence (AI) algorithms baricitinib was predicted to possess antiviral activity in addition to its known anti-inflammatory efficacy . Antiviral activity is predicted to arise from inhibition of the numb-associated kinase (NAK) AAK1 which is an important regulator of clathrin-mediated endocytosis. Inhibition of AAK1 would likely reduce the ability of viruses to infect lung cells, and is being proposed as a pharmacological mechanism that warrants further investigation as a treatment for SARS-CoV-2 infection. (GtoPdb)
SARS-CoV-2 and COVID-19: The powerful anti-inflammatory activity of baricitinib (and potentially other approved JAK inhibitors such as , and ) was suggested as potential therapeutic option to combat the immunopathological effects of SARS-CoV-2 infection in patients with severe COVID-19. A number of small-medium sized clinical studies have examined the effect of short-term baricitinib (or other JAK inhibitors) treatment in hospitalised patients with confirmed COVID-19. Such short term use of this drug during the course of SARS-CoV-2 infection (7-14 days) is not anticipated to cause serious side-effects. In March 2022, data reported from the largest of the baricitinib studies (part of the University of Oxford-led RECOVERY trial) indicated that it provided clinical benefit in hospitalised COVID-19 patients, including in those already receiving other standard care immunomodulatory treatments (e.g. , ) or the antiviral drug . This made baricitinib the 4th effective COVID-19 therapy to be identified by the RECOVERY trial.
Through the application of proprietary artificial intelligence (AI) algorithms baricitinib was predicted to possess antiviral activity in addition to its known anti-inflammatory efficacy . Antiviral activity is predicted to arise from inhibition of the numb-associated kinase (NAK) AAK1 which is an important regulator of clathrin-mediated endocytosis. Inhibition of AAK1 would likely reduce the ability of viruses to infect lung cells, and is being proposed as a pharmacological mechanism that warrants further investigation as a treatment for SARS-CoV-2 infection. (GtoPdb)
MOA
JAK enzymes are part of the family of tyrosine kinases that constitutively bind to the intracellular domains of cytokine receptors [A31382] and promote the signalling cascades of cytokines and growth factors involved in haematopoiesis, inflammation and immune function that are also implicated in the pathogenesis of rheumatoid arthritis [A31381]. Circulating proinflammatory cytokines bind to these cell surface receptors. Upon binding of extracellular cytokines and growth factors, JAKs are phosphorylated and activate signal transducers and activators of transcription (STATs). Through the signalling cascades, inflammatory cytokine and chemokine transcription is induced to form inflammatory mediators including IL-2, IL-6, IL-12, IL-15, IL-23, IFN-γ and GM-CSF [A31381]. ; ; Baricitinib selectively and reversibly inhibits JAK1 and JAK2 to modulates their signalling pathways, thereby reducing the phosphorylation and activation of STATs [FDA Label]. In isolated enzyme assays, baricitinib also exhibited an inhibitory effect on other types of JAK enzymes,Tyrosine Kinase 2 and JAK3, at higher concentrations needed for JAK1/2 inhibition.
DESCPRITION
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.
TOXICITY
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity and carcinogenic potential. Although unknown clinical relevance, bariticinib has shown to decrease the counts in lymphocytes, eosinophils and basophils as well as lymphoid depletion in organs/tissues of the immune system in mice, rats and dogs. Opportunistic infections related to demodicosis (mange) were observed in dogs at exposures approximately 7 times the human exposure. At doses approximately 6-36 times the indicated doses in humans, decreases in red blood cells was observed in mice, rats and dogs. ; ; In rat and rabbit reproductive toxicology studies, baricitinib was shown to reduce foetal growth/weight and produce skeletal malformations (at exposures of approximately 10 and 39 times the human exposure, respectively). Baricitinib decreased fertility and conception indices in a combined male/female rat fertility study. Decreased overall maing performance was likely due to altered reproductive functions of female rats, as there were no detectable changes on spermatogenesis or semen/sperm endpoints in male rats. In female rats, there were decreased numbers of corpora lutea and implantation sites, increased pre-implantation loss, and/or adverse effects on intrauterine survival of the embryos. In a dog pre- and postnatal development study, there were decreased pup weights at exposure 4 times the human exposure and decreased postnatal survival following exposure 21 times the human exposure. Baricitinib was detected in the milk of lactating rats {FDA Label]. ; ; Clinical relevance in humans is not yet established. All the adverse reactions associated with baricitinib are expected to occur dose-dependently.
DESCRIPTION
Baricitinib is an investigational JAK1 and 2 selective inhibitor. The compound is orally bioavailable.
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
Indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs as monotherapy or in combination with methotrexate.
(PKIDB)
DESCRIPTION
Potent and selective B-Raf, CDK16 and NEK9 inhibitor; anticancer; also targets human proteins in the SARS-CoV-2 interactome
(Tocris Bioactive Compound Library)
DESCRIPTION
IC50 Value: JAK1 (5.9 nM) and JAK2 (5.7 nM). Baricitinib, also known as INCB028050 or LY3009104, is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM). in vitro: INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. Significant efficacy, as assessed by improvements in clinical, histologic and radiographic signs of disease, was achieved in the rat adjuvant arthritis model with doses of INCB028050 providing partial and/or periodic inhibition of JAK1/JAK2 and no inhibition of JAK3. in vivo: The efficacy following daily oral administration of INCB028050 was assessed at doses of 1, 3, or 10 mg/kg based on its pharmacokinetic profile in this species. Disease severity was assessed periodically, scoring clinical signs of disease. These doses were based on the PK/PD relationship established with the IL-6 WBA, with the goal of inhibiting JAK1/2 signaling by no more than 50% for half of the day. Relative to vehicle-treated animals, increasing doses of INCB028050 inhibited disease scores by 24% (p < 0.05), 57% (p < 0.01), and 81% (p < 0.01), respectively. Baricitinib preferentially inhibits JAK1 and JAK2, with 10-fold selectivity over Tyk2 and 100-fold over JAK3. The observed effects of GLPG-0634 on the ACR20, albeit in a smaller study, appear to be at least as good as that seen with tofacitinib and superior to that of baricitinib, since baricitinib only moderately affect the ACR20 values in Phase IIa clinical studies. Clinical trial: Baricitinib (LY3009104, INCB28050) against JAK1/JAK2 starting phase IIb for rheumatoid arthritis
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
27
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
Clinical kinase drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
LINCS compound set
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
Tocris Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
46
Molecular Weight
371.12
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
1
Rotatable Bonds
5
Ring Count
4
Aromatic Ring Count
3
cLogP
1.1
TPSA
120.56
Fraction CSP3
0.38
Chiral centers
0.0
Largest ring
6.0
QED
0.72
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Targets
JAK1,JAK2
Pathway
Angiogenesis
Tyrosine Kinase/Adaptors
Chromatin/Epigenetic
JAK/STAT Signaling
Stem Cells
Cell Cycle/Checkpoint
Epigenetics
Protein Tyrosine Kinase/RTK
Stem Cell/Wnt
Target
JAK1
JAK2
JAK3
TYK2
CHK2
JAK1, JAK2
JAK1/2 inhibitor
JAK
COVID-19,JAK
Primary Target
JAK Kinase
MOA
Inhibitor
JAK inhibitor
Indication
rheumatoid arthritis
Orthogonal probe
Ruxolitinib
Control
INCB027753,INCB029843
INCB027753, INCB029843
Target subclass
TK
TK, TK
Target class
Protein kinase
Kinase, Kinase
Therapeutic Class
Antiviral Agents
Source data
