Baricitinib 1187594-09-7

Superiority:

Product Name: Baricitinib
Synonyms: aricitinib (LY3009104, INCB028050);Baricitinib Chemical Structure;Barrickini;1-(Ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyriMidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile;Baricitinib;INCB 028050;LY 3009104;Baricitinib (LY3009104)
CAS: 1187594-09-7
MF: C16H17N7O2S
MW: 371.41688
EINECS: 691-421-4
Product Categories: API;JAK;Inhibitor;JAK/STAT;Inhibitors;STAT
Mol File: 1187594-09-7.mol

Baricitinib Usage And Synthesis
Overview The oral, targeted synthetic DMARD (tsDMARD)[2], JAK1 and JAK2 inhibitor baricitinib (Olumiant) is a novel small molecule[1] that is approved in the EU[3] and Japan[4] for the treatment of adults with rheumatoid arthritis RA (moderate or severe active[3]), who responded inadequately to (other treatments[4]) or who were intolerant of C1 DMARD[3]. JAK is a tyrosine kinase that plays crucial roles[5] in cytokine receptor binding-triggered signal transduction activating the transcription factor signal transducers and activator of transcription (STAT). Activation of the receptor-bound JAKs is critical for initiating phosphorylation of the cytokine receptor and subsequent recruitment of one or more STATs. The phosphorylated STAT dimer is then actively and directly transported to the nucleus without involvement of any other kinases[6]. The JAK family consists of four members: JAK1, JAK2, JAK3, and TYK2. More than 40 different cytokines and growth factors have been shown to activate specific combination of JAKs and STATs. Genetic knockout studies have shown that JAKs and STATs have highly specific functions in the control of various immune responses. Baricitinib represents a selective inhibitor of JAKs with excellent potency and selectivity for JAK2 (IC50=5.7nM) and JAK1 (IC50=5.9nM), and less potency and selectivity for JAK3 (IC50 >400nM), or TYK2 (IC50=53nM)[7]. Although baricitinib potently inhibits JAKs, it does not significantly inhibit (<30% inhibition) a broad panel of 26 other kinases when tested at 200nM[7].

Indication and administration It is 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. Rheumatoid arthritis is a progressive autoimmune disease commonly associated with discomfort, disability, and joint damage. Throughout disease progression, the disease may further lead to joint erosions and deformities, causing premature mortality, functional impairment, and reduced quality of life[8].
In the EU[3] and Japan[4], oral baricitinib is approved (as monotherapy or in combination with methotrexate[3]) for the treatment of adults with (moderate to severe active[3]) RA who responded inadequately (to other treatments[4]), or who were intolerant of C1 DMARD[3]. The recommended dosage of baricitinib is 4 mg once daily; consideration may be given to a lower dosage of 2 mg once daily in patients who achieve sustained control of disease activity (with the higher dosage) and are eligible for dose tapering[3, 4]. The lower dosage is recommended for some patients, is appropriate for patients aged C75 years, and may also be appropriate for those with a history of chronic or recurrent infections[3]. In patients with mild or moderate hepatic impairment, no dose adjustments are required; the use of baricitinib is not recommended in patients with severe hepatic impairment[3].
Temporary or permanent discontinuation of baricitinib may be required for the management of AEs and laboratory abnormalities associated with baricitinib therapy[3, 4]. Local prescribing information should be consulted for further information, including contraindications, warnings, precautions, drug interactions and use in special patient populations.