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DDD107498 Sale

(Synonyms: DDD107498; DDD-498; M5717) 目录号 : GC17285

DDD107498 (DDD-498) 是一种有效的口服活性抗疟药,抑制寄生虫的多个生命周期阶段,对疟原虫的 EC50 为 1 nM。

DDD107498 Chemical Structure

Cas No.:1469439-69-7

规格 价格 库存 购买数量
5mg
¥1,890.00
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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

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实验参考方法

Antimalarial experiment [1]:

Malaria parasites

Various malaria parasites

Preparation method

This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0.0001 ~ 10 μM

Applications

DDD107498 showed excellent inhibition against 3D7 parasites, with the EC50 value of 1.0 nM. It also exhibited similar inhibition against several drug-resistant strains. Besides, DDD107498 was more potent than artesunate against a range of clinical isolates of both P. falciparum and P. vivax with the EC50 values of 0.81 nM and 0.51 nM respectively. In addition, the compound was non-toxic to human MRC5 and Hep-G2 cells at much higher concentrations.

Animal experiment [1]:

Animal models

NOD-scid IL-2R_null mice engrafted with human erythrocytes and infected with P. falciparum strain 3D70087/N9

Dosage form

0.1, 0.3, 0.6, 1 or 3 mg/kg/day; p.o.; for 4 days

Applications

In NOD-scid IL-2R_null mice engrafted with human erythrocytes and infected with P. falciparum strain 3D70087/N9, which were orally dosed daily for 4 days, the ED90 value on day 7 after infection was 0.95 mg/kg/day. Blood sampling from the infected SCID mice suggested the minimum parasiticidal concentration for DDD107498 was 10 ~ 13 ng/mL for asexual blood-stage infections.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

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

产品描述

DDD107498 is a potent and novel multiple-stage antimalarial agent against multiple life-cycle stages of the Plasmodium parasite. [1]
DDD107498 has an acceptable safety profile and good pharmacokinetic properties. Translation elongation factor 2 (eEF2) has been identified as the molecular target of DDD107498. The factor eEF2 is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. [1]
DDD107498 showed excellent activity against Plasmodium falciparum 3D7 parasites with EC50 value of 1.0 nM, EC90 value of 2.4 nM and EC99 value of 5.9 nM. Furthermore, DDD107498 was more potent than artesunate in ex vivo assays against a range of clinical isolates of both P. falciparum (median EC50 = 0.81 nM (range 0.29–3.29 nM), n = 44) and P. vivax (median EC50 = 0.51 nM (range 0.25–1.39 nM), n = 28) collected from patients with malaria from southern Papua. [1]
DDD107498 showed an EC50 < 1 nM against the liver schizont forms of P. berghei and Plasmodium yoelii. DDD107498 potently inhibited both male and female gamete formation from the gametocyte stage at similar concentrations [1.8 nM (95% CI 1.6–2.1 nM) and 1.2 nM (95% CI 0.8–1.6 nM)] respectively. DDD107498 blocked subsequent oocyst development in the mosquito after 7 days with an EC50 of 1.8 nM. [1]
DDD107498 had a 90% reduction in parasitaemia (ED90) of 0.57 mg/kg after a single oral dose in mice infected with the rodent parasite Plasmodium berghei. When orally dosed daily for 4 days, the ED90 on day 7 after infection was 0.95 mg/kg/day. Blood sampling from the infected SCID (severe combined immunodeficiency) mice suggested a minimum parasiticidal concentration for DDD107498 of 10–13 ng/ml for asexual blood-stage infections. [1]
In contrast, the compound was not toxic to human cells (MRC5 and Hep-G2 cells) at much higher concentrations (>20,000-fold selectivity). DDD107498 displayed excellent pharmacokinetic properties in preclinical species, including good oral bioavailability and long plasma half-life. DDD107498 showed good drug-like properties including metabolic stability when incubated with hepatic microsomes or hepatocytes from several species; good solubility in a range of different media; and low protein binding. [1]
Reference:
1.Baragaña B, Hallyburton I, Lee MC et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 2015 Jun 18;522(7556):315-20.

Chemical Properties

Cas No. 1469439-69-7 SDF
别名 DDD107498; DDD-498; M5717
化学名 6-fluoro-2-(4-(morpholinomethyl)phenyl)-N-(2-(pyrrolidin-1-yl)ethyl)quinoline-4-carboxamide
Canonical SMILES O=C(NCCN1CCCC1)C2=CC(C3=CC=C(CN4CCOCC4)C=C3)=NC5=CC=C(F)C=C52
分子式 C27H31FN4O2 分子量 462.56
溶解度 ≥ 14.05mg/mL in DMSO 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。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

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1 mg 5 mg 10 mg
1 mM 2.1619 mL 10.8094 mL 21.6188 mL
5 mM 0.4324 mL 2.1619 mL 4.3238 mL
10 mM 0.2162 mL 1.0809 mL 2.1619 mL
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