Upadacitinib hemihydrate Chemical Properties

InChI

InChI=1/C17H19F3N6O.H2O/c1-2-10-7-25(16(27)24-9-17(18,19)20)8-11(10)13-5-22-14-6-23-15-12(26(13)14)3-4-21-15;/h3-6,10-11,21H,2,7-9H2,1H3,(H,24,27);1H2/t10-,11+;/s3

InChIKey

VJSRYIXHEWRBKD-NFGOAHBONA-N

SMILES

C([C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1C1=CN=C2C=NC3NC=CC=3N12)C.O |&1:1,13,r|

Upadacitinib hemihydrate Usage And Synthesis

Description

Upadacitinib is a selective and reversible Janus kinase (JAK) inhibitor recently approved by the European Medicine Agency and the Food and Drug Administration for the treatment of rheumatoid arthritis (RA).

Mechanism of action

Upadacitinib hemihydrate's mechanism of action is defined by its targeted inhibition of key components of the intracellular signaling cascade, especially within the JAK/STAT pathway. This detailed mechanism underpins its clinical efficacy and safety profile. 

Clinical Use

Upadacitinib(RINVOQ) 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 (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Each prolonged-release tablet (RINVOQ 15 mg prolonged-release tablets.) contains upadacitinib hemihydrate, equivalent to 15 mg of upadacitinib.

Side effects

The most common adverse effects with upadacitinib in the trials included urinary and upper respiratory tract infections, altered liver function and nausea. Rare but serious adverse events included malignancy, thrombosis and gastrointestinal perforation. As with other JAK inhibitors, serious and sometimes fatal infections can occur with upadacitinib – pneumonia and cellulitis were the most commonly reported in the trials. Opportunistic infections such as tuberculosis, multi-dermatomal herpes zoster, oral candidiasis, cryptococcosis and pneumocystosis have also occurred.