VVD-118313 (C09-1184-819)

VVD-118313 (compound 5a) is a potent, selective JAK1 inhibitor. VVD-118313 targets an isoform-restricted allosteric cysteine to block JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 can be used for research of cancerIn VitroVVD-118313 (compound 5a; 0.01-10 μM; 3 h; primary human PBMCs) inhibits JAK1 by engagement of C817 and JAK2 by engagement of C838. VVD-118313 inhibits cysteine reactivity in a dose-dependent manner. VVD-118313 (2 µM, 2h) blocks IFNα-simulated STAT1 and IL-6-stimulated STAT3 phosphorylation in WT- or C810A-JAK1-expressing 22Rv1 cells. VVD-118313 also blocks the constitutive phosphorylation of WT- and C810A-JAK1. VVD-118313 (0.01-10 μM) selectively inhibits JAK1 signaling in primary human immune cells. VVD-118313 inhibits JAK1-dependent IFNα-pSTAT1, IL-6-pSTAT3, and IL-2-pSTAT5 pathways in human PBMCs in a dose-dependent manner. VVD-118313 (0.1-0.4 μM; 24 h) inhibits T-cell activation induction. VVD-118313 inhibits the activation of human T cells co-stimulated with αCD3/αCD28 by a reduction in the proportion of CD25 + T cells. VVD-118313 blocks the secretion of the Th1-polarizing cytokine IFNγ and increases the production of IL-2. VVD-118313 (0.1-0.5 μM; 2 h) inhibits on the production of pro-inflammatory cytokines and chemokines. VVD-118313 suppresses the induction of several pro-inflammatory chemokines, including CCL2/MCP-1, CXCL10/IP-10, and CCL4/MIP-1β. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: 22Rv1 cells Concentration: 0.01, 0.1, and 1 μM Incubation Time: 2 hours Result: Showed labeling of recombinant WT-JAK1 and C810A-JAK1, but not C817A-JAK1. Western Blot AnalysisCell Line: 22Rv1 cells Concentration: 2 µM Incubation Time: 2 hours Result: Inhibited WT- and C810A-JAK1 phosphorylation with even greater potency than STAT1/STAT3 phosphorylation.In VivoVVD-118313 (compound 5a; 25-50 mg/kg; i.h.; once) inhibits JAK1 signaling in TYK2 knockout mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: TYK2 knockout mice Dosage: 25 and 50 mg/kg Administration: Subcutaneous injection; once Result: Revealed 75% engagement of JAK1_C816 at 25 and 50 mg/kg, while other JAK1 cysteines were unaffected in reactivity.Form:SolidIC50& Target:JAK1. Specification: 0.99 Molecular Formula: C19H22Cl2N2O3S Molecular Weight: 429.36