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Cabamiquine

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Chemical Structure| 1469439-69-7 同义名 : DDD107498;DDD-498;MMV121;M5717
CAS号 : 1469439-69-7
货号 : A1155027
分子式 : C27H31FN4O2
纯度 : 99%+
分子量 : 462.559
MDL号 : MFCD32204416
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(227 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 DDD107498 is a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, targeting on PfeEF2 (P. falciparum translation elongation factor 2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. DDD107498 showed excellent activity against 3D7 parasites with EC50 value of 1nM. DDD107498 was more potent than artesunate in ex vivo assays against a range of clinical isolates of both P. falciparum with median EC50 value of 0.81nM and P. vivax with median EC50 value of 0.51nM. DDD107498 displayed excellent pharmacokinetic properties in preclinical species, including good oral bioavailability and long plasma half-life. DDD107498 was very active in several mouse models of malaria. It had a 90% reduction in parasitaemia (ED90) of 0.57mg/kg after a single oral dose in mice infected with the rodent parasite Plasmodium berghei. DDD107498 at concentration<1μM dose-dependently protein synthesis via eEF2, in the cytoplasm as opposed to the apicoplast, the site of action of tetracycline and azithromycin[3].
作用机制 DDD107498 targets protein synthesis via PfeEF2.[3]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.81mL

2.16mL

1.08mL

21.62mL

4.32mL

2.16mL
参考文献

[1]Baragaña B, Hallyburton I, et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 2015 Jun 18;522(7556):315-20.

[2]Baragaña B, Norcross NR, et al. Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy. J Med Chem. 2016 Nov 10;59(21):9672-9685. Epub 2016 Sep 10.

[3]Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R, Otto TD, Proto WR, Blagborough AM, Meister S, Wirjanata G, Ruecker A, Upton LM, Abraham TS, Almeida MJ, Pradhan A, Porzelle A, Luksch T, Martínez MS, Luksch T, Bolscher JM, Woodland A, Norval S, Zuccotto F, Thomas J, Simeons F, Stojanovski L, Osuna-Cabello M, Brock PM, Churcher TS, Sala KA, Zakutansky SE, Jiménez-Díaz MB, Sanz LM, Riley J, Basak R, Campbell M, Avery VM, Sauerwein RW, Dechering KJ, Noviyanti R, Campo B, Frearson JA, Angulo-Barturen I, Ferrer-Bazaga S, Gamo FJ, Wyatt PG, Leroy D, Siegl P, Delves MJ, Kyle DE, Wittlin S, Marfurt J, Price RN, Sinden RE, Winzeler EA, Charman SA, Bebrevska L, Gray DW, Campbell S, Fairlamb AH, Willis PA, Rayner JC, Fidock DA, Read KD, Gilbert IH. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 2015 Jun 18;522(7556):315-20. doi: 10.1038/nature14451. Erratum in: Nature. 2016 Sep 1;537(7618):122. PMID: 26085270; PMCID: PMC4700930.