UC-514321 是NSC370284 的结构类似物,且活性更高,靶向STAT3/5并选择性抑制TET1的表达。UC-514321 体内体外均表现出良好的抗急性髓系白血病的活性,并具有较低的毒性。
生物活性 | UC-514321, a structural analog of NSC370284 with higher activity, directly targetsSTAT3/5and repressesTET1expression, but not TET2 or TET3. UC-514321 has the potential to treat acute myeloid leukemia (AML) both in vitro and in vivo, with low toxicity[1]. |
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体外研究 (In Vitro) | UC-514321 increases apoptosis in AML cells not in normal HSPCs[1]. UC-514321 (0-500 nM, 48 h) inhibits AML cells viabilityTET1-signalingdependently[1].
Cell Viability Assay[1] Cell Line: | MONOMAC-6, THP-1, KOCL-48, KASUMI-1, ML-2, and NB4 cells. | Concentration: | 0-500 nM. | Incubation Time: | 48 hours. | Result: | Most significantly repressed MONOMAC-6 cell viability. Showed no inhibitory effect on the viability of TET1-low AML. |
RT-PCR[1] Cell Line: | MONOMAC-6 cells. | Concentration: | 0-500 nM. | Incubation Time: | 48 hours. | Result: | Functioned as TET1-transcription inhibitors in TET1-high AMLs and their anti-leukemic effects are TET1-dependent. |
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体内研究 (In Vivo) | UC-514321 (2.5 mg/kg, ip, once per day, for 10 days) exhibits more potent anti-tumor activity than NSC370284 in AML mice models[1].
Animal Model: | MLL-AF9-AML mice and AE9a-AML model[1]. | Dosage: | 2.5 mg/kg. | Administration: | IP., once per day, for 10 days. | Result: | Showed an improved therapeutic effect in AML mouse models in vivo. Prolonged the median survival over three fold. |
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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: Ethanol : 50 mg/mL(113.23 mM;Need ultrasonic) DMSO : 25 mg/mL(56.62 mM;Need ultrasonic) 配制储备液 1 mM | 2.2647 mL | 11.3235 mL | 22.6470 mL | 5 mM | 0.4529 mL | 2.2647 mL | 4.5294 mL | 10 mM | 0.2265 mL | 1.1323 mL | 2.2647 mL |
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此方案可获得 ≥ 2.5 mg/mL (5.66 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。
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