"目录号: HY-15315A
EpigeneticsStem Cell/WntJAK/STAT Signaling-
Baricitinib phosphate(INCB 028050; LY 3009104)是JAK和JAK2选择性抑制剂，IC50分别为5.9 nM和5.7 nM，比对JAK3 和Tyk2的抑制性强70倍和10倍，而对c-Met和Chk2无活性。
相关产品
Ruxolitinib-Baricitinib-Tofacitinib citrate-AZD-1480-WP1066-CYT387-Pacritinib-GLPG0634-Cerdulatinib-AT9283-Decernotinib-LY2784544-TG-101348-Upadacitinib-Itacitinib-
生物活性
Description
Baricitinib phosphate is a selective orally bioavailableJAK1/JAK2inhibitor withIC50of 5.9 nM and 5.7 nM, respectively.
IC50& Target
IC50: 5.9 nM (JAK1), 5.7 nM (JAK2), >400 nM (JAK3), 53 nM (Tyk2)[1]
In Vitro
In cell-based assays, Baricitinib (INCB028050) proves to be a potent inhibitor of JAK signaling and function. In PBMCs, Baricitinib inhibits IL-6-stimulated phosphorylation of the canonical substrate STAT3 (pSTAT3) and subsequent production of the chemokine MCP-1 with IC50values of 44 nM and 40 nM, respectively. In isolated naive T-cells, INCB028050 also inhibits pSTAT3 stimulated by IL-23 (IC50=20 nM). Importantly, this inhibition prevented the production of two pathogenic cytokines (IL-17 and IL-22) produced by Th17 cells-a subtype of helper T cells with demonstrable inflammatory and pathogenic properties-with an IC50value of 50 nM. In stark contrast, the structurally similar but ineffective JAK1/2 inhibitors INCB027753 and INCB029843 has no significant effect in any of these assays systems when tested at concentrations up to 10 μM[1].
In Vivo
Baricitinib (INCB028050) treatment, compares with vehicle, inhibits the increase in hind paw volumes during the 2 wk of treatment by 50% at a dose of 1 mg/kg and >95% at doses of 3 or 10 mg/kg. Because baseline paw volume measurements are taken on treatment day 0—in animals with significant signs of disease-it is possible to have >100% inhibition in animals showing marked improvement in swelling[1]. Baricitinib (0.7 mg/day) treated mice exhibits substantially reduced inflammation as assessed by H&E staining, reduced CD8 infiltration, and reduced MHC class I and class II expression when compared with vehicle-control treated mice. CD8+NKG2D+cells, critical effectors of disease in murine and human alopecia areata (AA), are greatly diminished in Baricitinib treated mice compare with vehicle control treated mice[2].
Clinical Trial
Eli Lilly and Company
Healthy Volunteers
January 2015
Phase 1
Eli Lilly and Company
Liver Diseases-Hepatic Insufficiency
June 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
October 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
October 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
August 2013
Phase 1
Eli Lilly and Company
Healthy Participants
November 2014
Phase 1
Matthew J Koster-Eli Lilly and Company-Mayo Clinic
Arteritis, Giant Cell
March 9, 2017
Phase 2
Eli Lilly and Company
Healthy
June 27, 2017
Phase 1
Eli Lilly and Company-Incyte Corporation
Psoriasis-Skin Diseases-Skin Diseases, Papulosquamous
December 2011
Phase 2
Eli Lilly and Company
Healthy Volunteers
May 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
July 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
September 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
August 2013
Phase 1
Eli Lilly and Company
Systemic Lupus Erythematosus
March 2016
Phase 2
National Cancer Institute (NCI)-National Institutes of Health Clinical Center (CC)
Chronic Graft vs Host Disease-Chronic Graft-Versus-Host Disease
April 8, 2016
Phase 1-Phase 2
Eli Lilly and Company
Rheumatoid Arthritis
October 2014
Phase 3
Eli Lilly and Company
Healthy Volunteers
October 2013
Phase 1
Eli Lilly and Company
Atopic Dermatitis
February 2016
Phase 2
Eli Lilly and Company-Incyte Corporation
Diabetic Kidney Disease
August 2012
Phase 2
Eli Lilly and Company
Rheumatoid Arthritis
June 2013
Phase 3
Eli Lilly and Company
Rheumatoid Arthritis
January 2013
Phase 3
Eli Lilly and Company
Rheumatoid Arthritis
October 2012
Phase 3
Eli Lilly and Company
Rheumatoid Arthritis
December 2012
Phase 3
Eli Lilly and Company
Rheumatoid Arthritis
November 2012
Phase 3
Eli Lilly and Company
Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE)-Juvenile Dermatomyositis (JDM)-Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset During Infancy (SAVI)-Aicardi-Goutières Syndrome (AGS)
Eli Lilly and Company
Healthy Volunteers
January 2015
Phase 1
Eli Lilly and Company
Liver Diseases-Hepatic Insufficiency
June 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
October 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
October 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
August 2013
Phase 1
Eli Lilly and Company
Healthy Participants
November 2014
Phase 1
Matthew J Koster-Eli Lilly and Company-Mayo Clinic
Arteritis, Giant Cell
March 9, 2017
Phase 2
Eli Lilly and Company
Healthy
June 27, 2017
Phase 1
Eli Lilly and Company-Incyte Corporation
Psoriasis-Skin Diseases-Skin Diseases, Papulosquamous
December 2011
Phase 2
Eli Lilly and Company
Healthy Volunteers
May 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
July 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
September 2013
Phase 1
Eli Lilly and Company
Healthy Volunteers
August 2013
Phase 1
Eli Lilly and Company
Systemic Lupus Erythematosus
March 2016
Phase 2
National Cancer Institute (NCI)-National Institutes of Health Clinical Center (CC)
Chronic Graft vs Host Disease-Chronic Graft-Versus-Host Disease
April 8, 2016
Phase 1-Phase 2
Eli Lilly and Company
Rheumatoid Arthritis
October 2014
Phase 3
Eli Lilly and Company
Healthy Volunteers
October 2013
Phase 1
Eli Lilly and Company
Atopic Dermatitis
February 2016
Phase 2
Eli Lilly and Company-Incyte Corporation
Diabetic Kidney Disease
August 2012
Phase 2
Eli Lilly and Company
Rheumatoid Arthritis
June 2013
Phase 3
Eli Lilly and Company
Rheumatoid Arthritis
January 2013
Phase 3
