SAG 21k是一种强效且口服生物可利用的Hedgehog信号通路激活剂，EC50值为0.4nM。
Cas No.:946002-48-8
Sample solution is provided at 25 µL, 10mM.
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SAG 21k is a potent and orally bioavailable Hedgehog signaling activator with an EC50 value of 0.4nM [1]. SAG 21k can induce a myofibroblast-like phenotype and promote the increased expression of α-smooth muscle actin (αSMA) and type I collagen (Col I) in the extracellular matrix[2]. SAG 21k has been widely used in mouse models to inhibit the formation of intramuscular fat and promote regenerative muscle growth[3].
In vitro, SAG 21k treatment (1μM) for 24h significantly induced the upregulation of Hedgehog response genes (Bmp4, Gli1, Gli2, Hhip, Ptch1, Ptch2) in Trastuzumab-resistant SKBR3 and HCC1954 cells, and promoted the expression of Nanog, Sox2, Bmi1 and Oct4[4]. The 24-hour treatment of 10nM SAG 21k promoted the migration of endoneurial fibroblasts and increased the expression of VEGF-A[5].
In vivo, SAG 21k treatment via intraperitoneal injection at a dose of 5mg/kg/day for one week promoted bone formation in segmental bone defects of mice and increased bone volume[6]. Daily intraperitoneal injection of SAG 21k (0.5mg/kg) twice a day for one week can alleviate the acute colitis induced by dextran sulfate sodium (DSS) in mice and increase the survival rate of the mice[7].
References:
[1] Brunton S A, Stibbard J H A, Rubin L L, et al. Potent agonists of the Hedgehog signaling pathway[J]. Bioorganic & medicinal chemistry letters, 2009, 19(15): 4308-4311.
[2] Lee J J, Perera R M, Wang H, et al. Stromal response to Hedgehog signaling restrains pancreatic cancer progression[J]. Proceedings of the National Academy of Sciences, 2014, 111(30): E3091-E3100.
[3] Liu X, Choi J, Moussa A, et al. Abstract Tu0084: Cilia-dependent Hedgehog Signaling Act as A Guardian against Limb Ischemia-induced Fatty Fibrosis[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2025, 45(Suppl_1): ATu0084-ATu0084.
[5] Faniku C, Kong W, He L, et al. Hedgehog signaling promotes endoneurial fibroblast migration and Vegf-A expression following facial nerve injury[J]. Brain research, 2021, 1751: 147204.
[4] Er I, Boz Er A B. Hedgehog pathway is a regulator of stemness in HER2-positive trastuzumab-resistant breast cancer[J]. International Journal of Molecular Sciences, 2024, 25(22): 12102.
[6] Rundle C H, Gomez G A, Pourteymoor S, et al. Sequential application of small molecule therapy enhances chondrogenesis and angiogenesis in murine segmental defect bone repair[J]. Journal of Orthopaedic Research®, 2023, 41(7): 1471-1481.
[7] Lee J J, Rothenberg M E, Seeley E S, et al. Control of inflammation by stromal Hedgehog pathway activation restrains colitis[J]. Proceedings of the National Academy of Sciences, 2016, 113(47): E7545-E7553.
SAG 21k是一种强效且口服生物可利用的Hedgehog信号通路激活剂，EC50值为0.4nM[1]。SAG 21k能够诱导肌成纤维细胞样表型，并促进细胞外基质中α-平滑肌肌动蛋白和I型胶原蛋白表达的增加[2]。SAG 21k已被广泛用于小鼠模型中，以抑制肌内脂肪形成并促进再生性肌肉生长[3]。
在体外，使用1μM的SAG 21k处理耐曲妥珠单抗的SKBR3和HCC1954细胞24小时，显著诱导了 Hedgehog反应基因的上调，并促进了Nanog、Sox2、Bmi1和Oct4的表达[4]。用10nM的SAG 21k处理 24小时，促进了endoneurial成纤维细胞的迁移，并增加了VEGF-A的表达[5]。
在体内，每日腹腔注射5mg/kg剂量的SAG 21k，持续一周，促进了小鼠节段性骨缺损的骨形成并增加了骨体积[6]。每日腹腔注射SAG 21k（0.5mg/kg）两次，持续一周，可减轻葡聚糖硫酸钠(DDS)诱导的小鼠急性结肠炎，并提高小鼠的存活率[7]。
| Cell experiment [1]: | |
Cell lines | HCC1954 cells |
Preparation Method | HCC1954 cells were grown in DMEM media supplemented with 10% FBS, 1% sodium pyruvate, and 2mM L-glutamine. The trastuzumab-resistant HCC1954 cells were generated by exposing the cells to increased doses (0.1-10μM) of trastuzumab for 3 months. The trastuzumab-resistant HCC1954 cells were treated with 1µM SAG 21k for 24 hours, and then RNA was extracted for analysis. |
Reaction Conditions | 1μM; 24h |
Applications | SAG 21k treatment significantly enhanced the expression of Nanog, Sox2, Bmi1, and Oct4 in trastuzumab-resistant HCC1954 cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | C57BL/6 mice (25-30g) were kept in temperature-controlled (21°C-25°C) and humidity-maintained (40%-70%) rooms with a 12-h light/dark cycle. Water and food were provided freely. Replace the regular drinking water of the mice with DSS solution (5%) for one week. Then, inject SAG 21k intraperitoneally into the mice at a dose of 0.5mg/kg, once every 12 hours for one week. The control group of mice will be injected with PBS. Collect the colon tissues of the mice for analysis and daily monitor the body weight of the mice. |
Dosage form | 0.5mg/kg; twice a day for 7 days; i.p. |
Applications | SAG 21k treatment alleviated the acute colitis induced by DSS in mice and inhibited the weight loss. |
References: | |
| Cas No. | 946002-48-8 | SDF | |
| Canonical SMILES | COC1=C(CN([C@@H]2CC[C@@H](NC)CC2)C(C3=C(Cl)C4=C(C(F)=CC=C4F)S3)=O)C=C(C5=CC=NC=C5)C=C1 | ||
| 分子式 | C29H28ClF2N3O2S | 分子量 | 556.07 |
| 溶解度 | DMSO : 40 mg/mL (71.93 mM; ultrasonic and warming and heat to 60°C) | 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 | 1.7983 mL | 8.9917 mL | 17.9833 mL |
| 5 mM | 359.7 μL | 1.7983 mL | 3.5967 mL |
| 10 mM | 179.8 μL | 899.2 μL | 1.7983 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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