Evofosfamide (TH-302)

Evofosfamide (TH-302)是一种选择性低氧激活的前体药物,靶向作用于实体瘤的hypoxic区域,IC50为19 nM,在缺氧条件下比在有氧条件下细胞毒性增强270倍,细胞色素P450代谢稳定。

Evofosfamide (TH-302) Chemical Structure

Evofosfamide (TH-302) Chemical Structure

CAS: 918633-87-1

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 2612.61 现货
10mg RMB 3028.64 现货
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批次: 纯度: 99.82%
99.82

Evofosfamide (TH-302)相关产品

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
H460 Cytotoxicity assay 2 hrs Cytotoxicity against human H460 cells under hypoxic condition after 2 hrs by clonogenic assay, IC90=0.1μM. 18257544
H460 Cytotoxicity assay 2 hrs Cytotoxicity against human H460 cells under hypoxic condition after 2 hrs by Alamar blue staining assay, IC50=0.019μM. 18257544
HT29 Cytotoxicity assay 2 hrs Cytotoxicity against human HT29 cells under hypoxic condition after 2 hrs by clonogenic assay, IC90=0.2μM. 18257544
H460 Cytotoxicity assay 2 hrs Cytotoxicity against human H460 cells under normoxic condition after 2 hrs by Alamar blue staining assay, IC50=5.1μM. 18257544
H460 Cytotoxicity assay 2 hrs Cytotoxicity against human H460 cells under normoxic condition after 2 hrs by clonogenic assay, IC90=30μM. 18257544
HT29 Cytotoxicity assay 2 hrs Cytotoxicity against human HT29 cells under normoxic condition after 2 hrs by clonogenic assay, IC90=40μM. 18257544
NCI-H460 Cytotoxicity assay 24 hrs Cytotoxicity against human NCI-H460 cells pretreated for 24 hrs under hypoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50=9.08μM. 28350997
HT-29 Cytotoxicity assay 24 hrs Cytotoxicity against human HT-29 cells pretreated for 24 hrs under hypoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50=49.51μM. 28350997
NCI-H460 Cytotoxicity assay 24 hrs Cytotoxicity against human NCI-H460 cells after 24 hrs under hypoxic condition by luminescence-based Cell-Titer Glo assay, IC50=0.0093μM. 29079474
NCI-H460 Cytotoxicity assay 24 hrs Cytotoxicity against human NCI-H460 cells after 24 hrs under normoxic condition by luminescence-based Cell-Titer Glo assay, IC50=6.65μM. 29079474
DU145 Cytotoxicity assay 2 hrs Cytotoxicity against human DU145 cells incubated for 2 hrs under hypoxic condition measured after 72 hrs by Alamar blue assay, IC50=4.14μM. 29259746
PC3 Cytotoxicity assay 2 hrs Cytotoxicity against human PC3 cells incubated for 2 hrs under hypoxic condition measured after 72 hrs by Alamar blue assay, IC50=6.49μM. 29259746
HEMC-SS Antiproliferative assay 24 hrs Antiproliferative activity against human HEMC-SS cells treated for 24 hrs under hypoxic condition followed by compound wash-out and incubated under normoxic condition for 48 hrs by alamar blue assay, IC50=0.13μM. 30199705
HEMC-SS Antiproliferative assay 24 hrs Antiproliferative activity against human HEMC-SS cells treated for 24 hrs under normoxic condition followed by compound wash-out and incubated under normoxic condition for 48 hrs by alamar blue assay, IC50=2.9μM. 30199705
MDA-MB-468 Cytotoxicity assay 4 hrs Cytotoxicity against human MDA-MB-468 cells incubated for 4 hrs under hypoxic condition followed by compound washout and measured after 5 days by SRB assay, IC50=0.0062μM. 30885680
SW620 Cytotoxicity assay 4 hrs Cytotoxicity against human SW620 cells incubated for 4 hrs under hypoxic condition followed by compound washout and measured after 5 days by SRB assay, IC50=0.052μM. 30885680
MDA-MB-468 Cytotoxicity assay 4 hrs Cytotoxicity against human MDA-MB-468 cells incubated for 4 hrs under aerobic condition followed by compound washout and measured after 5 days by SRB assay, IC50=4.403μM. 30885680
SW620 Cytotoxicity assay 4 hrs Cytotoxicity against human SW620 cells incubated for 4 hrs under aerobic condition followed by compound washout and measured after 5 days by SRB assay, IC50=20.6μM. 30885680
NCI-H460 Antiproliferative assay Antiproliferative activity against human NCI-H460 cells in presence of N2, IC50=2μM. 30295477
NCI-H460 Antiproliferative assay Antiproliferative activity against human NCI-H460 cells in presence of O2, IC50=25μM. 30295477
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生物活性

产品描述 Evofosfamide (TH-302)是一种选择性低氧激活的前体药物,靶向作用于实体瘤的hypoxic区域,IC50为19 nM,在缺氧条件下比在有氧条件下细胞毒性增强270倍,细胞色素P450代谢稳定。
体外研究(In Vitro)
体外研究活性 TH-302是低氧激活的前体药物,目前处于临床评测阶段。在含氧情况下,TH-302作用于椭圆形细胞比作用于单分子层细胞效果强很多。[2] 在有氧情况下,TH-302是非常有效的,且在肝脏微粒体中很稳定。在N2环境下,TH-302作用于人类肺癌H460细胞和人类结肠癌HT29细胞,具有高毒性。 TH-302抑制H460细胞和HT29细胞,IC90分别为0.1和0.2 μM。[1] TH-302作用于多发性骨髓瘤具有低氧选择性和剂量依赖性。在低氧条件下,TH-302诱导细胞周期停在G0/G1 期。通过下调cyclin D1/2/3, CDK4/6, p21cip-1, p27kip-1, 和 pRb表达来调节TH-302作用于细胞周期的影响,而CDK2表达对此没有作用效果。在低氧条件下,TH-302作用于人类和鼠多发性骨髓瘤细胞,诱导细胞凋亡,这种作用存在剂量依赖性。通过下调抗凋亡蛋白BCL-2和BCL-xL, 还有上调裂开的凋亡前体蛋白caspase-3,-8,和-9,及PARP的表达来调节TH-302激活的凋亡。与低氧环境下特殊的毒性相比,在含氧正常的环境下或者高氧环境下,TH-302 显示低毒性。[3]
细胞实验 细胞系 人类H460或HT29细胞
浓度 0.01 -1 μM
孵育时间 2小时
方法 指数生长的人类H460或HT29细胞按每孔3×105个细胞接种在60 mm有缺口的玻璃板上,在含10%FBS的RPMI培养基上生长2天。实验开始第一天,已知浓度TH-302溶液准备在完全培养基中,玻璃板上每孔加入2 mL溶液。玻璃板置于厌氧培养室或标准组织培养孵育器。在厌氧培养室中充满厌氧气体混合物(90% N2/5% CO2/5% H2),形成低氧环境。细胞和TH-302在37oC下温育2小时。处理到最后,移除板,用PBS冲洗,然后用胰蛋白酶-EDTA使胰蛋白酶化,在37oC下进行5分钟。分离的细胞用培养基和血清中和,然后在100g转速下旋转5分钟。细胞按1×106个细胞/mL再悬浮,然后稀释10倍。测定每组溶液的确切浓度。已知数目的细胞在第9天和第13天接种和置于孵育器中。菌落混合,用95%乙醇和0.25%结晶紫染色。计数超过50个细胞的菌落,测定存活率。
体内研究(In Vivo)
体内研究活性 实验移植第25天,TH302抑制肿瘤生长,抑制率达41% ,但是TH302和gemcitabine联用抑制肿瘤生长,抑制率达 96%。[1]TH-302按 6.25, 12.5, 25, 或50 mg/kg剂量腹腔注射到H460 NSCLC移植模型,每天处理一次,每周处理5次,持续2周,在第22天,肿瘤生长抑制率分别为43%, 51%, 75%,和 89%。TH-302 按100 mg/kg剂量作用于血细胞,处理后3天,血细胞下降,但是在处理后7天完全恢复。TH-302诱导细胞死亡,依赖于氧浓度,当作用于携带肿瘤的鼠在低氧浓度环境下,则毒性最高。TH-302作用于呼吸氧气需10% O2的动物,抑制肿瘤生长明显低于呼吸需95% O2的动物。TH-302处理后48小时, pimonidazole阳性区明显降低(对照组为6.3±1.2%,TH-302实验组为1.8±1.1%)。 [4]
动物实验 Animal Models 雌性NCI SCID鼠
Dosages 50 mg/kg
Administration 腹腔注射
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02020226 Unknown status
Solid Tumors
Threshold Pharmaceuticals
November 2013 Phase 1
NCT01833546 Completed
Solid Tumor|Pancreatic Cancer
Merck KGaA Darmstadt Germany|Threshold Pharmaceuticals
April 18 2013 Phase 1

化学信息&溶解度

分子量 449.04 分子式

C9H16Br2N5O4P

CAS号 918633-87-1 SDF Download Evofosfamide (TH-302) SDF
Smiles CN1C(=CN=C1[N+](=O)[O-])COP(=O)(NCCBr)NCCBr
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 90 mg/mL ( (200.42 mM); DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 90 mg/mL

Water : 10 mg/mL

摩尔浓度计算器

体内溶解度
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

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