LP-922056 是一种具有口服活性,强效的Notum Pectinacetylesterase抑制剂,在人和小鼠细胞测定中的EC50分别为 21 nM,55 nM。LP-922056 显着增加小鼠和大鼠股骨中轴的骨皮质厚度。
生物活性 | LP-922056 is an orally active, highly potentNotum Pectinacetylesteraseinhibitor withEC50s of 21 nM, 55 nM in human and mouse cellular assay, respectively. LP-922056 significantly increases midshaft femur cortical bone thickness in mice and rats[1][2]. |
IC50& Target | EC50: 21 nM (human Notum Pectinacetylesterase) and 55 nM (mouse Notum Pectinacetylesterase)[1] |
体外研究 (In Vitro) | NOTUM can inactivate WNTs by functioning as a WNT lipase[2].
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体内研究 (In Vivo) | LP-922056 (compound 44; 3-30 mg/kg; oral gavage; daily; for 25 days) causes an increase in cortical bone thickness at all doses[1]. LP-922056 (10 mg/kg; orally) achieves high Cmax(129 μM) and AUC (1533 μMoh)[1]. LP-922056 (10 mg/kg; daily diet; for 4 weeks) increases cortical bone thickness and strength in midshaft femur, bone mass in the femoral neck and vertebral body cortical shell in Twelve-week-old male mice[2].
Animal Model: | F1 male hybrid (129xC57) mice at 8.7 weeks of age[1] | Dosage: | 3, 10, 30 mg/kg | Administration: | Oral gavage; daily; for 25 days | Result: | Caused an increase in cortical bone thickness at all doses. |
Animal Model: | Mouse[1] | Dosage: | 10 mg/kg (Pharmacokinetic Analysis) | Administration: | Orally | Result: | Achieved high Cmax(129 μM) and AUC (1533 μMoh) while has low clearance (0.49 mL/minokg) and volume of distribution (0.13 L/kg). |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 125 mg/mL(415.59 mM;Need ultrasonic) 配制储备液 1 mM | 3.3247 mL | 16.6234 mL | 33.2469 mL | 5 mM | 0.6649 mL | 3.3247 mL | 6.6494 mL | 10 mM | 0.3325 mL | 1.6623 mL | 3.3247 mL |
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此方案可获得 ≥ 2.08 mg/mL (6.92 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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