944842-54-0 Usage
Description
Decernotinib is a potent and selective Janus kinase 3 (JAK3) inhibitor, designed to target and modulate the activity of JAK3, a key enzyme involved in the regulation of immune responses. Its selective action on JAK3 makes it a promising candidate for the treatment of autoimmune diseases, where the JAK3 pathway is often dysregulated.
Uses
Used in Pharmaceutical Industry:
Decernotinib is used as a therapeutic agent for the treatment of autoimmune diseases. Its selective inhibition of JAK3 helps to regulate the immune system, reducing inflammation and alleviating symptoms associated with various autoimmune conditions. This targeted approach may offer a more precise and effective treatment option compared to broader immunosuppressive therapies.
Biological Activity
decernotinib(vx-509)is a novel, potent and selective inhibitor of jak3 with ki value of 2 nm [1].the janus kinase family consists of four members: jak1, jak2, jak3, and tyk2. janus kinase 3 (jak3) is mainly expressed in lymphocytes, which are cells important to the immune response associated with many diseases, including rheumatoid arthritis (ra) [1].decernotinib(vx-509)is a novel, potent, selective and orally available jak3 inhibitor for the treatment of autoimmune diseases. vx-509 inhibited jak1, jak2, jak3, and tyk2 with ki values of 11, 13, 2 and 11 nm, respectively. in ht-2 or tf-1 cells, vx-509 inhibited jak3/1- or jak2-mediated phosphorylation of stat5 following stimulation with il-2 or gmcsf with ic50 values of 99 and 2600 nm, respectively [1].in the rat host versus graft (hvg) model, vx-509 at 50 mg/kg bid or 100 mg/kg qd significantly and dose-dependently inhibited popletial lymph node (pln) hyperplasia by 66% and 94%, respectively, relative to cyclosporin a (csa). vx-509 also significantly reduced cd25 expression. these results suggested that vx-509 showed significant dose-dependent immunosuppressive activity and effectively inhibited t-cell activation [1]. in the rat collagen-induced arthritis model, vx-509 dose-dependently reduced ankle swelling and paw weight, and improved paw histopathology scores. in oxazolone-induced delayed-type hypersensitivity mouse model, vx-509 reduced the t cell-mediated inflammatory response in skin [2].
references
[1]. farmer lj, ledeboer mw, hoock t, et al. discovery of vx-509 (decernotinib): a potent and selective janus kinase 3 inhibitor for the treatment of autoimmune diseases. j med chem, 2015, 58(18): 7195-7216. [2]. mahajan s, hogan jk, shlyakhter d, et al. vx-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease. j pharmacol exp ther, 2015, 353(2): 405-414.
Check Digit Verification of cas no
The CAS Registry Mumber 944842-54-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,4,4,8,4 and 2 respectively; the second part has 2 digits, 5 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 944842-54:
(8*9)+(7*4)+(6*4)+(5*8)+(4*4)+(3*2)+(2*5)+(1*4)=200
200 % 10 = 0
So 944842-54-0 is a valid CAS Registry Number.
944842-54-0Relevant articles and documents
Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases
Farmer, Luc J.,Ledeboer, Mark W.,Hoock, Thomas,Arnost, Michael J.,Bethiel, Randy S.,Bennani, Youssef L.,Black, James J.,Brummel, Christopher L.,Chakilam, Ananthsrinivas,Dorsch, Warren A.,Fan, Bin,Cochran, John E.,Halas, Summer,Harrington, Edmund M.,Hogan, James K.,Howe, David,Huang, Hui,Jacobs, Dylan H.,Laitinen, Leena M.,Liao, Shengkai,Mahajan, Sudipta,Marone, Valerie,Martinez-Botella, Gabriel,McCarthy, Pamela,Messersmith, David,Namchuk, Mark,Oh, Luke,Penney, Marina S.,Pierce, Albert C.,Raybuck, Scott A.,Rugg, Arthur,Salituro, Francesco G.,Saxena, Kumkum,Shannon, Dean,Shlyakter, Dina,Swenson, Lora,Tian, Shi-Kai,Town, Christopher,Wang, Jian,Wang, Tiansheng,Wannamaker, M. Woods,Winquist, Raymond J.,Zuccola, Harmon J.
, p. 7195 - 7216 (2015/10/05)
While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.
METHODS FOR TREATING INFLAMMATORY DISEASES AND PHARMACEUTICAL COMBINATIONS USEFUL THEREFOR
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METHODS FOR TREATING INFLAMMATORY DISEASES AND PHARMACEUTICAL COMBINATIONS USEFUL THEREFOR
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