Vosoritide (BMN 111) acetate is a natriuretic peptide receptor 2 (NPR2) agonist that acts on the proliferation and differentiation of chondrocytes to promote bone growth[1].
Vosoritide（0.1 μM；1 小时）acetate 降低软骨细胞中的 NPR2 磷酸化[2]。
Vosoritide（0.1 μM；6 天）acetate 改善软骨细胞分化并增加培养的 Fgfr3Y367C/+ 股骨的增殖生长板面积[2] 。
Vosoritide（10 μM；过夜）acetate 降低 ACH 生长板软骨细胞中的 ERK1/2 激活[3]。
Western Blot Analysis[2]
| Cell Line: | Chondrocyte cultures |
| Concentration: | 0.1 μM |
| Incubation Time: | 1 hour |
| Result: | Led to reduction in NPR2 phosphorylation. |
Western Blot Analysis[3]
| Cell Line: | Chondrocyte |
| Concentration: | 10 μM |
| Incubation Time: | Overnight |
| Result: | Prevented FGF-mediated increase in ERK1/2 phosphorylation. |
Vosoritide（皮下注射；800 μg/kg；每日一次；20 天）acetate 治疗可改善 Fgfr3 功能获得性突变小鼠的骨骼参数[3]。
| Animal Model: | Fgfr3Y367C/+ mice[3] |
| Dosage: | 800 μg/kg |
| Administration: | Subcutaneous injection; 800 μg/kg; once daily; 20 days |
| Result: | Observed phenotypic changes including flattening of the skull, elongation of the snout, improvement of the anterior crossbite, larger paws and digits, and longer and straightened tibias and femurs. |
[1]. Leia C. Shuhaibar, et al. Phosphatase inhibition by LB-100 enhances BMN-111 stimulation of bone growth. JCI Insight. 2021 May 10;6(9):e141426.
[2]. Shuhaibar LC, et al. Phosphatase inhibition by LB-100 enhances BMN-111 stimulation of bone growth. JCI Insight. 2021 May 10;6(9):e141426.
[3]. Lorget F, et al. Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. Am J Hum Genet. 2012 Dec 7;91(6):1108-14.