WAY 316606 is a potent inhibitor of Secreted Frizzled-Related Protein I (sFRP-1), with an IC50 value of 0.5μM[1]. WAY 316606 can regulate the activation of Wnt signaling pathway by inhibiting sFRP-1 activity, and is used as a key regulator to modulate osteoclastogenesis and bone resorption[2]. WAY 316606 can be used as a hair growth promoter in human hair follicle organ models to induce hair growth in humans[3].
In vitro, WAY 316606 treatment at 2μM for 72 hours stimulated the proliferation of human neural stem cells, and increased the activity of the Wnt pathway[4]. Treatment with 2μM WAY 316606 for 7 days significantly increased mineralization and the expression of mineralization-related genes in periodontal ligament fibroblasts, and improved mineral homeostasis[5]. Treatment with 2μM WAY 316606 for 12 hours can partially alleviate the growth inhibition of U251 cells induced by H2O2 (1 mM; 12 hours), reduce cell apoptosis, and increase cell viability[6].
In vivo, WAY 316606 treatment (0.5μM/5μL) via intraneural injection per 3 days for 2 weeks significantly promoted the axon regrowth of transected nerves in mice following nerve transection[7]. In female Sprague-Dawley rats, WAY 316606 exhibited high plasma clearance (77mL/min/kg) following a single intravenous bolus dose (2mg/kg)[8].
References:
[1] Moore W J, Kern J C, Bhat R, et al. Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides[J]. Journal of medicinal chemistry, 2009, 52(1): 105-116.
[2] Ma Q, Wang S, Xie Z, et al. The SFRP1 Inhibitor WAY‐316606 Attenuates Osteoclastogenesis Through Dual Modulation of Canonical Wnt Signaling[J]. Journal of Bone and Mineral Research, 2020, 37(1): 152-166.
[3] Hawkshaw N J, Hardman J A, Haslam I S, et al. Identifying novel strategies for treating human hair loss disorders: cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the dermal papilla of human scalp hair follicles[J]. PLoS biology, 2018, 16(5): e2003705.
[4] Donega V, van der Geest A T, Sluijs J A, et al. Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors[J]. Nature communications, 2022, 13(1): 1036.
[5] Gopinathan G, Foyle D, Luan X, et al. The Wnt antagonist SFRP1: a key regulator of periodontal mineral homeostasis[J]. Stem cells and development, 2019, 28(15): 1004-1014.
[6] Xing Z, Ni Y, Zhao J, et al. Hydrogen peroxide-induced secreted frizzled-related protein 1 gene demethylation contributes to hydrogen peroxide-induced apoptosis in human U251 glioma cells[J]. DNA and cell biology, 2017, 36(5): 347-353.
[7] Yao X, Kong L, Qiao Y, et al. Schwann cell-secreted frizzled-related protein 1 dictates neuroinflammation and peripheral nerve degeneration after neurotrauma[J]. Cell Reports Medicine, 2024, 5(11).
[8] Bodine P V N, Stauffer B, Ponce-de-Leon H, et al. A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation[J]. Bone, 2009, 44(6): 1063-1068.
WAY 316606是一种强效分泌型卷曲相关蛋白1（sFRP-1）抑制剂，IC50值为0.5μM[1]。WAY 316606通过抑制sFRP-1活性调控Wnt信号通路激活，可作为关键调节剂影响破骨细胞生成和骨吸收过程[2]。WAY 316606在人毛囊器官模型中作为毛发促进剂诱导毛发生长[3]。
在体外，2μM的WAY 316606处理72小时可刺激人神经干细胞增殖并增强Wnt通路活性[4]。2μM的WAY 316606处理7天能显著促进牙周膜成纤维细胞矿化，上调矿化相关基因表达并改善矿物质稳态[5]。2μM的WAY 316606处理12小时可部分缓解H2O2（1mM，12小时）诱导的U251细胞生长抑制，减少细胞凋亡并提高细胞活力[6]。
在体内，小鼠神经横断后通过神经内注射WAY 316606（0.5μM/5μL；每3天一次；持续2周）可显著促进轴突再生[7]。雌性Sprague-Dawley大鼠单次静脉推注2mg/kg的WAY 316606后，WAY 316606表现出高血浆清除率（77mL/min/kg）[8]。