Publications

Metotreksata yetersiz yanıt veren romatoid artritli hastalarda baricitinibin 24 haftadaki güvenlik ve etkinliği

Ann Rheum Dis. 2015;74(2):333–340

Keystone EC,

Taylor PC,

Drescher E,

Schlichting DE,

Beattie SD,

Berclaz PY,

Lee CH,

Fidelus-Gort RK,

Luchi ME,

Rooney TP,

Macias WL,

Genovese MC.

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies.

This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...

Keywords:

• JAK,
• Baricitinib,
• Phase 2

Romatoid artritte tedavi için terapötik fırsat olarak TNFα ve IL-17’nin kombine inhibisyonu: Yeni bir bispesifik antikorun geliştirilmesi ve nitelendirilmesi.

Arthritis Rheumatol. 2015;67(1):51–62

Fischer JA,

Hueber AJ,

Wilson S,

Galm M,

Baum W,

Kitson C,

Auer J,

Lorenz S,

Moelleken J,

Bader M,

Tissot AC,

Tan SL,

Seeber S,

Schett G

Single cytokine inhibition, e.g. TNFα or IL-6, has fundamentally improved the therapeutic armamentarium for the treatment of RA; yet clinically meaningful responses are achieved in only about half of RA patients treated. In addition, it is now well established that the pathogenesis of RA involves multiple mechanisms of cell activation and cell recruitment. These two factors have led to the emergence of the concept of dual specificity, sparking interest in the biologic arena, with a focus o...

Keywords:

• IL-17,
• TNF

Anti-inflamatuar genlerin p38 MAP kinaz ve MAP kinaz kinaz 6 tarafından farklı regülasyonu

Journal of Inflammation 2014, 11:14

Hammaker D,

Boyle DL,

Topolewski K et al

Several p38α inhibitors have been developed and evaluated in RA. However, despite pre-clinical data showing promise, the compounds have been shown to have little therapeutic efficacy. Previous studies have suggested this may be a result of inhibitors blocking the role of p38 in limiting inflammation. Previous studies by the same authors have shown that the targeting of MKK3 or MKK 6, which are the upstream activators of p38, may be superior to p38 blockade as the anti-inflammatory effects ...

Keywords:

• p38 MAPK,
• Preclinical,
• MOA

Alternatif p38 MAPKlar Kollajen ile Uyarılmış Artrit için Gereklidir

Arthritis and Rheumatology Vol66, No. 5, May2014 pp 1208-1217

Criado G,

Risco A,

Alsina-Beauchamp D et al

MAPK family proteins are regulatory proteins, affecting processes such as synthesis and release of proinflammatory molecules which contribute to the pathogenesis of RA. In particular, the p38 MAPK protein family is central to proinflammatory cytokine production. There are four member of the p38 group; p38α, p38β, p38γ and p38δ. This study sought to evaluate p38γ and p38δ deficiency in mice CIA model. In p38γ-/- or p38δ-/- mice, the percentage of mic...

Keywords:

• p38 MAPK,
• Preclinical,
• MOA

Osteoartrit benzeri durumlarda TAK1 ve/veya JAK inhibisyonu insan mezenkimal kök hücrelerinin bozulmuş kıkırdak farklılaşmasını düzeltebilir

Tissue Engineering Part A doi:10/1089/ten.TEA.2013.0553

Van Beuningen HM,

de Vries-van Melle ML,

Vitters El et al.

As it is nonvascularized and noninnervated, articular cartilage has a limited capacity to repair which presents a major clinical problem. In order to circumvent this inability to repair, stem cells can be placed into the joint or stimulated within the bone marrow. However, as the cartilage requiring repair is often in diseased joints, the factors involved in the disease state are potentially non-beneficial to the chondrogenesis of mesenchymal stem cells. In this study van Beuningen et al. invest...

Keywords:

• JAK,
• Preclinical,
• MOA

Oral Btk inhibitörü İbrutinibOsteoklast Aracılı Kemik Kaybına Karşı Koruyucudur

Bone 2014;60:8-15

Shinohara M,

Chang BY,

Buggy JJ et al

Ibrutinib is a first-in-class, orally available Btk (Bruton’s tyrosine kinase) inhibitor which has been shown to be effective in the treatment against certain types of leukemia and autoimmune disorders. Btk regulates the expression of genes involved in the differentiation and function of osteoclasts, and therefore inhibiting Btk suppresses osteoclastic bone resorption. Results from in vitro testing showed the suppressive effects on osteoclasts and murine models of RA showed ibrutinib treatment p...

Keywords:

• BTK,
• Preclinical,
• Bone

Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor

Clinical Immunology 2007; 124:244-57

Pine PR,

Chang B,

Schoettler N,

et al.

This study investigated the capacity of the novel oral spleen tyrosine kinase (Syk) inhibitor R406, and its prodrug R788 (fostamatinib), to suppress the reversed passive Arthrus reaction (RPA) and collagen-induced arthritis (CIA) in rats. R406 (0.1, 1, 5 and 10 mg/kg) and R788 (10 and 30 mg/kg) reduced the cutaneous RPA reaction and inflammatory oedema in a dose-dependent manner, with statistically significant reductions in extravascular leakage and tissue swelling (72% reduction with R406 10 mg...

Keywords:

• SYK,
• Preclinical,
• Bone