RepSox (Synonyms: E 616452, RepSox, SJN 2511) |
| رقم الكتالوجGC16793 |
مثبط انتقائي لـ ALK5
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 446859-33-2
Sample solution is provided at 25 µL, 10mM.
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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.
| 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: | |
| Cas No. | 446859-33-2 | SDF | |
| المرادفات | E 616452, RepSox, SJN 2511 | ||
| Chemical Name | 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 | ||
| Formula | C17H13N5 | M.Wt | 287.32 |
| الذوبان | ≥ 14.35 mg/mL in DMSO, ≥ 47.9 mg/mL in EtOH with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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