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MRX-2843 (Synonyms: UNC2371) 纯度: 99.70%
MRX-2843 (UNC2371) 是一种具有口服活性的、ATP 竞争性的 MERTK 和 FLT3 酪氨酸激酶抑制剂 (TKI),IC50 分别为 1.3 nM 和 0.64 nM。
MRX-2843 Chemical Structure
CAS No. : 1429882-07-4
规格 | 价格 | 是否有货 | 数量 |
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10 mM * 1 mL in DMSO | ¥3010 | In-stock | |
1 mg | ¥1000 | In-stock | |
5 mg | ¥2800 | In-stock | |
10 mg | ¥4800 | In-stock | |
25 mg | ¥9800 | In-stock | |
50 mg | ¥14000 | In-stock | |
100 mg | 询价 | ||
200 mg | 询价 |
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MRX-2843 相关产品
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- Drug Repurposing Compound Library
- Orally Active Compound Library
- Anti-Blood Cancer Compound Library
生物活性 |
MRX-2843 (UNC2371) is an orally active, ATP-competitive dual MERTK and FLT3 tyrosine kinases inhibitor (TKI) with enzymatic IC50s of 1.3 nM for MERTK and 0.64 nM for FLT3, respectively[1]. |
IC50 & Target |
MERTK, FLT3[1] |
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体外研究 (In Vitro) |
In the Kasumi-1 cell line, treatment with MRX-2843 results in dose-dependent inhibition of MERTK phosphorylation. Decreased phosphorylation is evident at concentrations as low as 10 nM, with near-complete abrogation of MERTK activation at 100 to 300 nM. Similarly, treatment of Kasumi-1 cells with MRX-2843 mediates inhibition of downstream signaling through pathways important for tumor cell survival and proliferation. MRX-2843 treatment results in a decrease in relative cell numbers, with an IC50 of 143.5±14.1 nM, indicating that MRX-2843 significantly inhibits tumor cell proliferation and/or survival. Similarly, there are 34.1%±5.6% and 67.1%±2.7% apoptotic and dead cells in NOMO-1 cultures treated with 150 nM or 300 nM MRX-2843, respectively, compare with 6.8%±0.7% in vehicle-treated cultures (P<0.001). Treatment with 50 nM and 100 nM MRX-2843 results in 62.3%±6.4% and 84.1%±7.8% inhibition of colony formation, respectively, in Kasumi-1 cultures (P<0.01). Similarly, in NOMO-1 cultures, colony formation is inhibited by 54.8%±18.1% in response to treatment with 100 nM MRX-2843 (P<0.001). In MOLM-14 cells, treatment with MRX-2843 inhibits phosphorylation of FLT3 and downstream signaling through STAT5, ERK1/2, and AKT. Activation of FLT3 and its signaling pathways is almost completely abrogated by treatment with 50 nM MRX-2843, indicating somewhat higher cellular potency against FLT3 relative to MERTK[1]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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体内研究 (In Vivo) |
MRX-2843 is 78% orally bioavailable at a dose of 3 mg/kg with a Cmax of 1.3 μM and a t1/2 of 4.4 hours. In MOLM-14 parental xenografts, both quizartinib and MRX-2843 increase median survival compare with that of vehicle-treated mice (172.5 days versus 40 days and 121 days versus 36 days, respectively, P<0.001). In this model, quizartinib is more effective than MRX-2843 (P<0.005), although higher doses of MRX-2843 are not evaluated. In MOLM-14:D835Y xenografts, quizartinib prolongs survival compare with that of vehicle-treated mice, but the effect is minimal (median survival 45 days vs. 36 days, P<0.001). In MOLM-14:F691L xenografts, treatment with MRX-2843 prolongs survival by almost 2-fold in NSG and NSGS mice (median survival 87 vs. 44.5 days and 87 vs. 48 days, respectively, P<0.005). Increased survival is observed in response to treatment with MRX-2843 versus quizartinib, but the difference is only significant in NSG mice[1]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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Clinical Trial |
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分子量 |
488.67 |
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Formula |
C29H40N6O |
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CAS 号 |
1429882-07-4 |
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运输条件 |
Room temperature in continental US; may vary elsewhere. |
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储存方式 |
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溶解性数据 |
In Vitro:
DMSO : 31.25 mg/mL (63.95 mM; Need ultrasonic) 配制储备液
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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。 In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
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参考文献 |
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Cell Assay [1] |
Cell lines are cultured (10,000 cells/sample) in 0.35% Noble agar on a 0.5% Noble agar base layer and overlaid with cRPMI containing kinase inhibitor (including MRX-2843) or vehicle. The overlying medium is replaced 2 to 3 times per week, and vehicle treatment is assessed in duplicate. After 14 days or 21 days (Kasumi-1 cells only), colonies are stained with 1 mg/mL nitrotetrazolium blue for 4 hours and counted using a colony counter. Mononuclear cells are isolated from human cord blood and samples from acute myeloid leukemia (AML) patients. Patient samples are cultured in triplicate at a density of 1×106 cells/mL in MethoCult H4434 Classic Methylcellulose-Based Medium with Recombinant Cytokines for Human Cells containing MRX-2843 or vehicle. Colonies are counted after 10 days using the colony counter. Cord blood cells are incubated for 1 hour in serum-free Iscove’s modified Dulbecco’s medium (IMDM) supplemented with BIT 9500 Serum Substitute, low-density lipoproteins, and 2-ME, and then cultured in triplicate at a density of 2×106 cells/mL in Methocult H4434 methylcellulose containing MRX-2843 or vehicle. Colonies are manually counted in a blinded manner after 14 days[1]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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Animal Administration [1] |
Mice are used in this study. Established leukemia cell lines or mononuclear cells isolated from samples from patients with acute myeloid leukemia (AML) (1×106 to 2.5×106 per mouse) are suspended in PBS and injected into the tail veins of mice to establish xenografts. All mice are 4 to 6 months of age at the time of injection and are male, with the exception of the NOMO-1, MOLM-14:D835Y, and MOLM-14:F691L NSG xenografts, which are established in female mice. Myeloblasts are detected in peripheral blood (patient-derived xenografts) or bone marrow (MOLM-14 xenografts) samples after staining with a FITC-conjugated anti-human CD45 Ab. Samples are analyzed by flow cytometry using a Gallios flow cytometer and Kaluza software. After engraftment, the mice are weighed and treated once daily with MRX-2843, quizartinib, or vehicle administered by oral gavage in a volume of 10 mL/kg. When mice appear ill or lost more than 20% of their body weight, they are euthanized[1]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
参考文献 |
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