SU 16f is a potent tyrosine kinase inhibitor that inhibits VEGF-R2, FGF-R1, and PDGFRβ, with IC50 values of 0.14, 2.29, and 0.01μM, respectively [1]. SU 16f can inhibit PDGFRβ phosphorylation, resulting in a significant reduction in the phosphorylation of ERK1/2 and STAT3, while the expression of CLDN1 decreased[2]. SU 16f has been widely used as a model compound for molecular docking to analyze the characteristic sites and develop a series of related receptor tyrosine kinase inhibitors[3].
In vitro, SU 16f pretreatment (20μM) for 8 hours significantly inhibited the promoting effect of gastric cancer-derived mesenchymal stem cell (GC-MSC) conditioned medium on the cell proliferation and migration of SGC-7901 cells[4]. SU 16f treatment (5μM; 14 days) eliminated the inhibitory effects of PDGF-BB on BMP2-induced osteogenic differentiation of primary periosteum-derived progenitor cells (PDCs)[5]. Treatment with 10μM SU 16f for 72 hours significantly inhibited the migration of mouse brain vascular pericytes (MBVP) induced by PDGFβ[6].
In vivo, SU 16f administration (2mg/kg/day) via intraperitoneal injection for five consecutive days restored the formation of beige adipose tissue in tamoxifen (TMX)-induced Sma-CreERT2; R26-mTmG male mice exposed to cold environment[7]. Intrathecal injection of a 10μl 3mM SU 16f solution (dissolved in 0.1M PBS containing 3% DMSO) at a rate of 1μl/4s, administered daily for eight consecutive days, blocked the PDGFRβ pathway, inhibited fibrotic scar formation, and promoted axonal regeneration and motor function recovery after spinal cord injury in mice[8].
References:
[1] Sun L, Tran N, Liang C, et al. Design, synthesis, and evaluations of substituted 3-[(3-or 4-carboxyethylpyrrol-2-yl) methylidenyl] indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases[J]. Journal of medicinal chemistry, 1999, 42(25): 5120-5130.
[2] Pang S, Wu R, Lv W, et al. Use of a pH-responsive imatinib mesylate sustained-release hydrogel for the treatment of tendon adhesion by inhibiting PDGFRβ/CLDN1 pathway[J]. Bioactive Materials, 2024, 38: 124-136.
[3] Kammasud N, Boonyarat C, Tsunoda S, et al. Novel inhibitor for fibroblast growth factor receptor tyrosine kinase[J]. Bioorganic & medicinal chemistry letters, 2007, 17(17): 4812-4818.
[4] Huang F, Wang M, Yang T, et al. Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression[J]. Journal of cancer research and clinical oncology, 2014, 140(11): 1835-1848.
[5] Wang X, Matthews B G, Yu J, et al. PDGF modulates BMP2‐induced osteogenesis in periosteal progenitor cells[J]. JBMR plus, 2019, 3(5): e10127.
[6] Li Z, Zheng M, Yu S, et al. M2 macrophages promote PDGFRβ+ pericytes migration after spinal cord injury in mice via PDGFB/PDGFRβ pathway[J]. Frontiers in Pharmacology, 2021, 12: 670813.
[7] Benvie A M, Lee D, Steiner B M, et al. Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice[J]. Nature Communications, 2023, 14(1): 1806.
[8] Li Z, Yu S, Liu Y, et al. SU16f inhibits fibrotic scar formation and facilitates axon regeneration and locomotor function recovery after spinal cord injury by blocking the PDGFRβ pathway[J]. Journal of Neuroinflammation, 2022, 19(1): 95.
SU 16f是一种有效的酪氨酸激酶抑制剂，可抑制VEGF-R2、FGF-R1和PDGFRβ，IC50值分别为0.14、2.29和0.01μM [1]。SU 16f能抑制PDGFRβ磷酸化，从而导致ERK1/2和STAT3磷酸化显著减少，同时CLDN1表达降低[2]。SU 16f已被广泛用作分子对接的模型化合物，用于分析特征位点并开发一系列相关的受体酪氨酸激酶抑制剂[3]。
在体外，用SU 16f（20μM）预处理8小时，能显著抑制胃癌来源间充质干细胞条件培养基对SGC-7901细胞增殖和迁移的促进作用[4]。SU 16f处理（5μM；14天）消除了PDGF-BB对BMP2诱导的原代骨膜来源祖细胞（PDCs）成骨分化所产生抑制作用[5]。用10μM SU 16f处理72小时，显著抑制了PDGFβ诱导的小鼠脑血管周细胞(MBVP)的迁移[6]。
在体内，连续五天通过腹腔注射SU 16f（2mg/kg/day），恢复了暴露于寒冷环境的他莫昔芬(TMX)诱导的Sma-CreERT2; R26-mTmG雄性小鼠中米色脂肪组织的形成[7]。连续8天每天以1μl/4s的速率髓鞘内注射10μl的3mM SU 16f溶液（溶于含3% DMSO的0.1M PBS中）可阻断PDGFRβ通路抑制纤维化瘢痕形成，促进小鼠脊髓损伤后轴突再生和运动功能恢复[8]。