SLW131

SLW131 is a CCR7 antagonist with a K i value of 9.85 nM. SLW131 inhibits CCL19 -induced Go protein activation with an IC₅₀ of 29.4 μM, and suppresses β-arrestin2 recruitment with an IC₅₀ of 6.0 μM. SLW131 serves as a probe for investigating the biological functions of CCR7 in cells. SLW131 is applicable to research related to rheumatoid arthritis ^[1].

In Vitro, SLW131 (Compound 10) binds to the intracellular allosteric site of CCR7 in cell-free CCR7GSSGNluc membranes with a single-digit nanomolar affinity (Ki = 9.85 nM), showing 10-fold higher potency than Cmp2105^[1]. SLW131 engages the intracellular allosteric site of CCR7 in live HEK293T cells transiently expressing CCR7GSSG_Nluc with a single-digit nanomolar affinity (Ki = 6.53 nM), demonstrating improved cellular target engagement compared to Cmp2105^[1]. SLW131 inhibits CCL19-induced β-arrestin2 recruitment in HEK293T cells transiently expressing hCCR7, while Cmp2105 shows no inhibitory activity^[1]. SLW131 (10 μM; 1 h) inhibits CCL19-directed 3D collagen migration of primary mature BMDCs, while Cmp2105 shows no inhibitory activity^[1].

References:
[1]. Wurnig SL, et al. A Fluorescent Probe Enables the Discovery of Improved Antagonists Targeting the Intracellular Allosteric Site of the Chemokine Receptor CCR7. J Med Chem. 2025;68(4):4308-4333.