VVD-118313

• CAT Number: I042824
• CAS Number: 2875046-27-6
• Molecular Formula: C19H22Cl2N2O3S
• Molecular Weight: 429.36
• Purity: ≥95%
• Synonyms: 1-[3-(3,4-dichlorophenyl)piperidin-1-yl]-3-[(3R)-1-methylsulfonylpyrrolidin-3-yl]prop-2-yn-1-one
• InChI: InChI=1S/C19H22Cl2N2O3S/c1-27(25,26)23-10-8-14(12-23)4-7-19(24)22-9-2-3-16(13-22)15-5-6-17(20)18(21)11-15/h5-6,11,14,16H,2-3,8-10,12-13H2,1H3/t14-,16?/m0/s1
• InChIKey: OUPVMVHXMWBFDP-LBAUFKAWSA-N
• SMILES: CS(=O)(=O)N1CCC(C1)C#CC(=O)N2CCCC(C2)C3=CC(=C(C=C3)Cl)Cl

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 cancer[1]. VVD-118313 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
VVD-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[1].
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[1].
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[1].
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[1].
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[1].
VVD-118313 (compound 5a; 25-50 mg/kg; i.h.; once) inhibits JAK1 signaling in TYK2 knockout mice[1].

Reference

[1]. Kavanagh ME, et, al. Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine. Nat Chem Biol. 2022 Sep 12.
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