| Identification | Back Directory | [Name]
Decernotinib | [CAS]
944842-54-0 | [Synonyms]
VX 509
CS-1650
VRT 831509
adelatinib
Decernotinib
VX-509;VRT-831509
Decernotinib(VX-509)
VX-509;? VRT-831509; ADELATINIB
Decernotinib (VX-509,adelatinib)
(R)-2-((2-(1H-Pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide
(2R)-2-Methyl-2-[[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-4-pyrimidinyl]amino]-N-(2,2,2-trifluoroethyl)butanamide
Butanamide, 2-methyl-2-[[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-4-pyrimidinyl]amino]-N-(2,2,2-trifluoroethyl)-, (2R)- | [Molecular Formula]
C18H19F3N6O | [MDL Number]
MFCD27987896 | [MOL File]
944842-54-0.mol | [Molecular Weight]
392.38 |
| Chemical Properties | Back Directory | [density ]
1.363±0.06 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light, stored under nitrogen | [solubility ]
insoluble in H2O; ≥16.95 mg/mL in DMSO; ≥2.92 mg/mL in EtOH with ultrasonic | [form ]
solid | [pka]
12.36±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Decernotinib is a potent and selective Janus kinase 3 inhibitor for treatment of autoimmune diseases. | [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]. | [in vivo]
Decernotinib (VX-509, 10, 25, or 50 mg/kg, p.o.) significantly and dose-dependently inhibits the increases in ankle diameter and paw weight occuring in response to collagen injections in rats. Decernotinib potently alleviates cartilage damage and bone resorption in rats. Decernotinib (10, 25, or 50 mg/kg, p.o., b.i.d.) suppresses ear edema in a mouse model of delayed-type hypersensitivity[1]. | [IC 50]
JAK3: 2.5 nM (Ki); JAK1: 11 nM (Ki); Tyk2: 11 nM (Ki); JAK2: 13 nM (Ki); FLT3: 1 μM (Ki); ROCK I: 1.5 μM (Ki); GSK3β: 1.8 μM (Ki); CDK2/CycA: 2.6 μM (Ki); PknB: 8 μM (IC50) | [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. |
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