寄端霉素 |(1aR,3Z,13S,14S,15aR)-9,13,14-trihydroxy-11-methoxy-6-methyl-5,6,13,14,15,15a-hexahydro-2H-oxireno[h][2]benzoxacyclotetradecine-2,8(1aH)-dione |cas:76958-67-3|西域试剂

寄端霉素 ,(1aR,3Z,13S,14S,15aR)-9,13,14-trihydroxy-11-methoxy-6-methyl-5,6,13,14,15,15a-hexahydro-2H-oxireno[h][2]benzoxacyclotetradecine-2,8(1aH)-dione ,≥98% (HPLC)

产品编号：SIGMA-H1667| CAS NO：76958-67-3| 分子式：C19H22O8| 分子量：378.3732

Hypothemycin 是由真菌产生的聚酮化合物，是一种多激酶抑制剂，对 VEGFR2/VEGFR1，MEK1/MEK2，FLT-3，PDGFRβ/PDGFRα 和 ERK1/ERK2 的 Ki 值分别为 10/70 nM，17/38 nM, 90 nM，900 nM/1.5 μM 和 8.4/2.4 μM。

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货号	包装	价格	库存与货期	购买量	操作
SIGMA-H1667		￥6271.00	杭州北京（现货）
SIGMA-H1667		￥2034.00	杭州北京（现货）

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英文名称

(1aR,3Z,13S,14S,15aR)-9,13,14-trihydroxy-11-methoxy-6-methyl-5,6,13,14,15,15a-hexahydro-2H-oxireno[h][2]benzoxacyclotetradecine-2,8(1aH)-dione

CAS编号

76958-67-3

产品描述

外观性状

Solid

溶解性

DMSO: soluble

溶解性数据

In Vitro:

DMSO : 100 mg/mL (264.29 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.6429 mL	13.2146 mL	26.4292 mL
5 mM	0.5286 mL	2.6429 mL	5.2858 mL
10 mM	0.2643 mL	1.3215 mL	2.6429 mL

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, 6 months; -20°C, 1 month。-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。

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
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (6.61 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (6.61 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (6.61 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (6.61 mM，饱和度未知) 的澄清溶液。
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 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (6.61 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (6.61 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。

*以上所有助溶剂都可在西域网站选购。

体外研究

Hypothemycin inhibits eosinophilic EOL1 cell carrying mutations in FIP1L1-PDGFRα, acute myeloid leukemia MV-4-11 cell carrying mutations in FLT3-ITD, melanoma COLO829 cell carrying mutations in BRAF V600E, HUVEC cell carrying mutations in VEGFR, mastocytoma P815 cell carrying mutations in c-KIT D814Y, NSCLC A459 cell carrying mutations in KRAS, and ovarian SKOV-3 cell carrying mutations in HER2 with IC₅₀s of 0.4 nM, 6 nM, 50 nM, 70 nM, 370 nM, 6.0 μM, and 7.0 μM, respectively。

体内研究

Hypothemycin (10 mg/kg) kills T. brucei in infected mice, completely curing the infection in one third of animals, although high doses of Hypothemycin (>10 mg/kg) leads to side effects.

XIYU has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Adult female Balb/c mice (weighing 18–22 g) infected with T. brucei
Dosage:	10 mg/kg
Administration:	Administered once daily via intraperitoneal injection for 7 days.
Result:	Showed a dose-dependent reduction in parasitemia in infected mice. Prolonged survival of infected mice over 30 days, with a cure rate of 33%.

细胞实验

生物活性

Hypothemycin, one of the highly oxygenated analogues in the group of 14-membered resorcylic acid lactones (RAL), has minor antifungal and cytotoxic activity and exhibits an in vitro anti-malarial activity with an IC50 of 2.2 μg/mL. Hypothemycin is also reported to selectively and irreversibly inhibit protein kinases that contain a conserved cysteine residue (Cys166) that is located within the ATP-binding domain. Though this group accounts for less then 10% of all identified kinases, there are several targets implicated in aberrant cellular proliferation such as ERKs, MEK, FMS-like tyrosine kinase protein (FLT), and platelet-derived growth factor receptors (PDGFR). In cell culture, hypothemycin displays potent cytotoxicity against cancer cell lines that are dependent on certain activating kinase mutations. Additionally, hypothemycin demonstrates significant tumor growth inhibition in at least three separate murine xenograft models. Hypothemycin also inhibits the production of several cytokines such as IL2, IL6, IFNγ, and TNFα.

动物实验

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.6429 mL	13.2146 mL	26.4292 mL
5 mM	0.5286 mL	2.6429 mL	5.2858 mL
10 mM	0.2643 mL	1.3215 mL	2.6429 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

储存条件

储存条件: -20°C

运输方式: 冰袋运输，根据产品的不同，可能会有相应调整。

化学品安全说明书(MSDS)

下载MSDS

质检证书(COA)

参考文献

[1] Ying Gao, et al. Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp

[2] Ki Hwan Park, et al. Hypothemycin inhibits tumor necrosis factor-α production by tristetraprolin-dependent down-regulation of mRNA stability in lipopolysaccharide-stimulated macrophages

[3] Liangxiong Xu, et al. Antifungal activity of hypothemycin against Peronophythora litchii in vitro and in vivo

[4] Mari Nishino, et al. Hypothemycin, a fungal natural product, identifies therapeutic targets in Trypanosoma brucei [corrected]

[5] R Camacho, et al. Hypothemycin inhibits the proliferative response and modulates the production of cytokines during T cell activation