In vitro: In biochemical assays, Upadacitinib is 74-fold more selective for JAK-1 than for JAK-2 (which is involved in erythropoiesis) and 58-fold more selective for JAK-1 than for JAK-3 (which is involved in immunosurveillance). The enhanced selectivity of Upadacitinib for JAK-1 over JAK-2 and JAK-3 may offer an improved benefit–risk profile in patients with RA range.
In vivo: AbbVie’s second JAK inhibitor in development Upadacitinib has been described as a second-generation inhibitor. Multiple-dose Phase I studies are completed in 2013. In phase I trials, Upadacitinib is found to be safe and well-tolerated up to multiple doses of 24 mg twice daily using the immediate release formulation. Upadacitinib exposure is dose proportional in the evaluated multiple dose.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||22 mg/mL in DMSO|
Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib.
Mohamed MF, et al. Br J Clin Pharmacol. 2017 Oct;83(10):2242-2248. PMID: 28503781.
JAK inhibitors: A broadening approach in rheumatoid arthritis.
Lam S. Drugs Today. 2016 Aug;52(8):467-469. PMID: 27722215.
|Related JAK Products|
Peficitinib (ASP015K, JNJ-54781532) is an orally bioavailable JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.
FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM.
WHI-P97 is a JAK3 inhibitor with an estimated Ki value of 0.09 microM from modeling studies and a measured IC50 value of 2.5 microM in EGFR kinase inhibition assays.
SAR-20347 is a potent dual inhibitor of JAK1 and TYK2 with IC50 values of 23 and 0.6 nM, respectively.
Itacitinib, also known as INCB39110 or INCB039110, is a potent JAK1 tyrosine kinase inhibitor.
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