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.
|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||10mM in DMSO|
Novel Oral Therapies for Psoriasis and Psoriatic Arthritis.
Yiu ZZ, et al. Am J Clin Dermatol. 2016 Jun;17(3):191-200. PMID: 26923915.
|Related JAK Products|
Itacitinib, also known as INCB39110 or INCB039110, is a potent JAK1 tyrosine kinase inhibitor.
Solcitinib is a selective Janus kinase 1 (JAK1) inhibitor, for the treatment of psoriasis, lupus, and ulcerative colitis. Targer: JAK1
PF-06651600 is a potent and irreversible JAK3-selective inhibitor with an IC50 of 33.1 nM but without activity (IC50 > 10 000 nM) against JAK1, JAK2, and TYK2.
Upadacitinib (ABT-494) is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders with an IC50 of 43 nM.
Ruxolitinib phosphate(INCB018424 phosphate) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.