RepSox
(Synonyms: 2-[3-(6-甲基-2-吡啶基)-1H-吡唑-4-基]-1,5-萘啶,E-616452;SJN 2511;E616452;SJN2511;E 616452;SJN-2511,ALK5 Inhibitor II) 目录号 : GC16793
RepSox是一种有效的选择性转化生长因子-β受体I/激活素样激酶5（TGF-β-RI/ALK5）抑制剂，IC50为23nM。RepSox抑制ALK5自身磷酸化，IC50 值为4nM。
Cas No.:446859-33-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | Mouse embryonic fibroblasts (MEFs) |
Preparation Method | Mouse embryonic fibroblasts (MEFs) were isolated from C57BL/6 mouse embryos at embryonic day 13.5. The fully confluent cells were cultured in differentiation-inducing medium containing 10μM CHIR99021, 10μM RepSox, or 50μM Forskolin for 8-10 days, with the medium changed every 2 days. The differentiated cells were washed with PBS and then fixed with 4% paraformaldehyde for 20 minutes at room temperature. Oil Red O solution and water were mixed in a ratio of 3:2 and layered on the cells for 10 minutes. After staining, the excess Oil Red O was washed with 60% isopropanol, then washed with deionized water, and images were taken under a microscope. |
Reaction Conditions | 10μM; 8-10d |
Applications | Many adipocyte-like cells appeared in MEFs treated with RepSox, Forskolin treatment induced weak adipocyte differentiation, whereas CHIR99021 treatment had no effect. |
| Animal experiment [2]: | |
Animal models | GFAP-Cre:Rosa26-tdTomato mice |
Preparation Method | Induction of the transformation of Enteric glial cells (EGCs) into enteric neurons was performed using 10-week-old adult GFAP-Cre:Rosa26-tdTomato mice in situ. RepSox was dissolved in 0.5% CMC-Na (sodium carboxymethyl cellulose), and the control group was given only 0.5% CMC-Na. Mice were gavaged with RepSox (3 or 10 mg/kg/day) and 0.5% CMC-Na for 2 consecutive weeks. The mice were fasted for 20h with access to water ad libitum. Before the test of intestinal motility, each mouse was given carmine and then free access to water and food ad libitum. The time of the first red stool appearance in the mice was recorded, as well as the number of defecations within 6 h and the wet and dry weight of the feces. After mouse intestinal motility testing, all mice were sacrificed, and the small intestine LMMP tissue was exfoliated to perform immunofluorescence staining. |
Dosage form | 3 or 10mg/kg/day for 2 weeks; p.o. |
Applications | Administration of RepSox significantly promoted the conversion of enteric glial cells to neurons in the enteric nervous system and influenced gastrointestinal motility in adult mice. |
References: | |
RepSox is a potent and selective inhibitor of transforming growth factor-β receptor I/activin-like kinase 5 (TGF-β-RI/ALK5) with an IC50 of 23nM[1]. RepSox inhibits ALK5 autophosphorylation with an IC50 of 4nM[2]. RepSox can be used to study obesity and related metabolic diseases (such as type 2 diabetes)[3].
In vitro, treatment of mouse embryonic fibroblasts with RepSox (10μM) for 8-10days induced the generation of many adipocytes, enhanced brown preadipocyte differentiation, and promoted the browning of white preadipocytes[4]. Treatment of osteosarcoma cell lines (HOS and 143B cells) with RepSox (0-200μM) for 24-96h inhibited cell proliferation in a time- and concentration-dependent manner, significantly inhibited colony size and number, increased the expression of pro-apoptotic Bax protein, and decreased the expression of anti-apoptotic Bcl-2 protein[5].
In vivo, RepSox (3, 10mg/kg) was administered to adult mice via oral gavage for 2 weeks, which significantly promoted the transformation of enteric glial cells into enteric nervous system neurons, affected gastrointestinal motility, and enhanced gastrointestinal motility in mice[6]. RepSox (2, 5mg/kg) was administered intraperitoneally to osteoporosis (OP) model mice for 4 weeks, which prevented bone loss in vivo, reduced the number of osteoclasts, and lowered serum CTX-1 (a bone resorption marker) [7].
References:
[1] Madipally D J. Role of Epicardial Adipose Tissue Secreted Interleukin-34 in Fibroblast to Myofibroblast Transdifferentiation and Atrial Fibrosis[M]. East Carolina University, 2021.
[2] Mansour M A, Hassan G S, Serya R A T, et al. Advances in the discovery of activin receptor-like kinase 5 (ALK5) inhibitors[J]. Bioorganic Chemistry, 2024: 107332.
[3] Takeda Y, Harada Y, Yoshikawa T, et al. Chemical compound-based direct reprogramming for future clinical applications[J]. Bioscience Reports, 2018, 38(3): BSR20171650.
[4] Tu W, Fu Y, Xie X. RepSox, a small molecule inhibitor of the TGFβ receptor, induces brown adipogenesis and browning of white adipocytes[J]. Acta Pharmacologica Sinica, 2019, 40(12): 1523-1531.
[5] He D, Gao J, Zheng L, et al. TGF β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway[J]. International Journal of Oncology, 2021, 59(5): 1-13.
[6] Shi C, Lian J, Zhang B, et al. TGFβR-1/ALK5 inhibitor RepSox induces enteric glia-to-neuron transition and influences gastrointestinal mobility in adult mice[J]. Acta Pharmacologica Sinica, 2023, 44(1): 92-104.
[7] Mei L, Sang W, Chen Z, et al. Small molecule inhibitor RepSox prevented ovariectomy‐induced osteoporosis by suppressing osteoclast differentiation and bone resorption[J]. Journal of Cellular Physiology, 2018, 233(12): 9724-9738.
RepSox是一种有效的选择性转化生长因子-β受体I/激活素样激酶5（TGF-β-RI/ALK5）抑制剂，IC50为23nM[1]。RepSox抑制ALK5自身磷酸化，IC50 值为4nM[2]。RepSox可用于肥胖和相关代谢疾病（如2型糖尿病）的研究[3]。
在体外，RepSox（10μM）处理小鼠胚胎成纤维细胞8-10天，诱导了许多脂肪样细胞生成，增强了棕色前脂肪细胞分化，促进了白色前脂肪细胞褐变[4]。RepSox（0-200μM）处理骨肉瘤细胞系（HOS和143B细胞）24-96h，以时间和浓度依赖性方式抑制了细胞增殖，显著抑制了集落大小和数量，增加了促凋亡Bax蛋白的表达，降低了抗凋亡Bcl-2蛋白的表达[5]。
在体内，RepSox（3, 10mg/kg）通过灌胃处理成年小鼠2周，显著促进了肠神经胶质细胞向肠神经系统神经元的转化，并影响了小鼠的胃肠蠕动，增强了胃肠动力[6]。RepSox（2, 5mg/kg）通过腹膜内注射治疗骨质疏松症（OP）模型小鼠4周，防止了体内骨质流失，减少了破骨细胞的数量，降低了血清CTX-1（骨吸收标志物）[7]。
| Cas No. | 446859-33-2 | SDF | |
| 别名 | 2-[3-(6-甲基-2-吡啶基)-1H-吡唑-4-基]-1,5-萘啶,E-616452;SJN 2511;E616452;SJN2511;E 616452;SJN-2511,ALK5 Inhibitor II | ||
| 化学名 | 2-[5-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine | ||
| Canonical SMILES | CC1=CC=CC(=N1)C2=C(C=NN2)C3=NC4=C(C=C3)N=CC=C4 | ||
| 分子式 | C17H13N5 | 分子量 | 287.32 |
| 溶解度 | ≥ 14.35 mg/mL in DMSO, ≥ 47.9 mg/mL in EtOH with gentle warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4804 mL | 17.4022 mL | 34.8044 mL |
| 5 mM | 0.6961 mL | 3.4804 mL | 6.9609 mL |
| 10 mM | 0.348 mL | 1.7402 mL | 3.4804 mL |
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