SN-38

别名: NK012

SN-38 (NK012)是CPT-11的一种活性代谢物,抑制DNA topoisomerase I,DNA合成,并造成频繁的DNA单链断裂。SN-38 可诱导自噬。

SN-38 Chemical Structure

SN-38 Chemical Structure

CAS: 86639-52-3

规格 价格 库存 购买数量
10mM (1mL in DMSO) 794.43 现货
10mg 573.3 现货
50mg 1040.13 现货
1g 7944.3 现货
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SN-38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
DU145 Function assay 0.1 to 0.5 uM 24 hrs Inhibition of HDAC in human DU145 cells assessed as upregulation of p21waf1 expression at 0.1 to 0.5 uM after 24 hrs by Western blot analysis 23622981
MIA PaCa Antiproliferative assay 96 hrs Antiproliferative activity against human MIA PaCa cells after 96 hrs, IC50 = 0.006 μM. 18276141
DU145 Antiproliferative assay 96 hrs Antiproliferative activity against human DU145 cells after 96 hrs, IC50 = 0.004 μM. 18276141
human tumor HL60 cell-line Function assay 3 days In-vitro inhibitory concentration for human tumor HL60 cell-line was determined using SRB assay after 3 days of incubation, IC50=19 nM 15913996
HT29 Antiproliferative assay 96 hrs Antiproliferative activity against human HT29 cells after 96 hrs, IC50 = 0.012 μM. 18276141
H460 Antiproliferative assay 1 hr Antiproliferative activity against human H460 cells after 1 hr of drug exposure measured after 72 hrs, IC50 = 0.22 μM. 18424133
HT29 Antiproliferative assay 1 hr Antiproliferative activity against human HT29 cells after 1 hr of drug exposure measured after 72 hrs, IC50 = 0.67 μM. 18424133
HT29 Antiproliferative assay 1 hr Antiproliferative activity against BCRP overexpressing mitoxantrone-resistant human HT29 cells after 1 hr of drug exposure measured after 72 hrs, IC50 = 11.5 μM. 18424133
PC6 Antiproliferative assay 6 days Antiproliferative activity against human PC6 cells carrying pRC after 6 days, IC50 = 0.00043 μM. 19254843
HCT116 Antiproliferative assay 3 days Antiproliferative activity against human HCT116 cells after 3 days, IC50 = 0.00055 μM. 19254843
QG56 Antiproliferative assay 3 days Antiproliferative activity against human QG56 cells after 3 days, IC50 = 0.0028 μM. 19254843
NCI-H460 Antiproliferative assay 3 days Antiproliferative activity against human NCI-H460 cells after 3 days, IC50 = 0.0033 μM. 19254843
BCRP Antiproliferative assay 6 days Antiproliferative activity against human PC6 expressing BCRP cells after 6 days, IC50 = 0.0051 μM. 19254843
KB3-1 Cytotoxicity assay 4 days Cytotoxicity against human KB3-1 cells after 4 days by MTT method, IC50 = 0.004 μM. 19303306
KBV1 Cytotoxicity assay 4 days Cytotoxicity against MDR1 overexpressing human KBV1 cells after 4 days by MTT method, IC50 = 0.046 μM. 19303306
KBH5.0 Cytotoxicity assay 4 days Cytotoxicity against BCRP overexpressing human KBH5.0 cells after 4 days by MTT method, IC50 = 0.3 μM. 19303306
NCI-H460 Antiproliferative assay 1 hr Antiproliferative activity against human NCI-H460 cells after short term exposure for 1 hr measured after 72 hrs in drug-free medium, IC50 = 0.13 μM. 19530720
gastric cancer cells Growth inhibition assay 72 hrs Growth inhibition of human gastric cancer cells after 72 hrs by sulforhodamine B assay, GI50 = 0.066 μM. 20884089
lung cancer cells Growth inhibition assay 72 hrs Growth inhibition of human lung cancer cells after 72 hrs by sulforhodamine B assay, GI50 = 0.066 μM. 20884089
colon cancer cells Growth inhibition assay 72 hrs Growth inhibition of human colon cancer cells after 72 hrs by sulforhodamine B assay, GI50 = 0.066 μM. 20884089
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells expressing alpha5beta3 integrin assessed as cell survival after 72 hrs by SRB assay, IC50 = 0.0026 μM. 22959246
A2780 Cytotoxicity assay 72 hrs Cytotoxicity against human A2780 cells overexpressing alpha5beta3 integrin assessed as cell survival after 72 hrs by SRB assay, IC50 = 0.009 μM. 22959246
DU145 Cytotoxicity assay 72 hrs Cytotoxicity against human DU145 cells assessed as inhibition of cell viability after 72 hrs by MTS assay, IC50 = 0.11 μM. 23622981
A549 Cytotoxicity assay 3 days Cytotoxicity against human A549 cells assessed as growth inhibition after 3 days by SRB assay, IC50 = 0.00272 μM. 24529870
HCT116 Cytotoxicity assay 3 days Cytotoxicity against human HCT116 cells assessed as growth inhibition after 3 days by SRB assay, IC50 = 0.031 μM. 24529870
HT-29 Cytotoxicity assay 3 days Cytotoxicity against human HT-29 cells assessed as growth inhibition after 3 days by SRB assay, IC50 = 0.10667 μM. 24529870
HEK293 Cytotoxicity assay 72 hrs Intrinsic cytotoxicity against HEK293 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IG50 = 0.005 μM. 25272055
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.00428 μM. 25835359
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.01854 μM. 25835359
HCT15 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT15 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.008 μM. 27060760
U251 Cytotoxicity assay 72 hrs Cytotoxicity against human U251 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.021 μM. 27060760
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.03 μM. 27060760
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.054 μM. 27060760
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.515 μM. 27060760
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 1.97 μM. 27060760
NCI-H460 Cytotoxicity assay 24 hrs Cytotoxicity against human NCI-H460 cells pretreated for 24 hrs under normoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50 = 0.05 μM. 28350997
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 = 0.06 μM. 28350997
HT-29 Cytotoxicity assay 24 hrs Cytotoxicity against human HT-29 cells pretreated for 24 hrs under normoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50 = 2.74 μM. 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 = 3.71 μM. 28350997
NCI-H460 Cytotoxicity assay 72 hrs Cytotoxicity against human NCI-H460 cells assessed as growth reduction under hypoxic condition after 72 hrs by MTT assay, IC50 = 0.047 μM. 28740613
NCI-H460 Cytotoxicity assay 72 hrs Cytotoxicity against human NCI-H460 cells assessed as growth reduction under normoxic condition after 72 hrs by MTT assay, IC50 = 0.05 μM. 28740613
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as growth reduction under normoxic condition after 72 hrs by MTT assay, IC50 = 0.096 μM. 28740613
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as growth reduction under hypoxic condition after 72 hrs by MTT assay, IC50 = 0.119 μM. 28740613
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 0.00078 μM. 30115492
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by SRB assay, IC50 = 0.00162 μM. 30115492
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.0001 μM. 30169038
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.2 μM. 30169038
SaoS2 Function assay TP_TRANSPORTER: drug resistance(Imatinib mesylate) in BCRP-expressing SaoS2 cells, IC50 = 0.176 μM. 15059881
HT-29 Function assay In vitro inhibitory concentration required against HT-29 human colon cancer cells, IC50 = 0.0273 μM. 12617927
PC-6/SN2-5H Function assay TP_TRANSPORTER: uptake in membrane vesicle from PC-6/SN2-5H cells, Km = 4 μM. 11688982
MDA-MB-435 Function assay Inhibition against MDA-MB-435 S human breast cancer cells in the presence of 30 mg/mL HSA, IC50 = 0.05 μM. 11052802
MDA-MB-435 Function assay Inhibition against MDA-MB-435 S human breast cancer cells in the absence of albumin, IC50 = 0.005 μM. 11052802
human H460 cell Growth inhibition assay Inhibition of human H460 cell growth, IC50=80 nM 16913706
human Bel-7402 liver cancer cell line Function assay Inhibitory concentration against human Bel-7402 liver cancer cell line, IC50=3.19 μM 15808456
human HCT116 colon cancer cell line Function assay Inhibitory concentration against human HCT116 colon cancer cell line, IC50=7 nM 15808456
PC-3 carcinoma cell line Growth inhibition assay Concentration required to inhibit growth of human prostate PC-3 carcinoma cell line, IC50=35.6 nM 15454230
NSCLC-H460 Cytotoxic assay Cytotoxicity against human non-small-cell lung carcinoma cell line H460 (NSCLC-H460), IC50=80 nM 11563925
human lung cancer cell line (A549) Cytotoxic assay In Vitro cytotoxicity against human lung cancer cell line (A549) 11334569
human colon cancer cell line (WiDr) Cytotoxic assay In Vitro cytotoxicity against human colon cancer cell line (WiDr), IC50=14 nM 11334569
human ovarian cancer cell line (SK-OV-3) Cytotoxic assay In Vitro cytotoxicity against human ovarian cancer cell line (SK-OV-3), IC50=11 nM 11334569
human stomach cancer cell line (MKN45) Cytotoxic assay In Vitro cytotoxicity against human stomach cancer cell line (MKN45), IC50=8 nM 11334569
human lung cancer cell line (H128) Cytotoxic assay In Vitro cytotoxicity against human lung cancer cell line (H128), IC50=6 nM 11334569
human breast cancer cell line (SK-BR-3) Cytotoxic assay In Vitro cytotoxicity against human breast cancer cell line (SK-BR-3), IC50=4 nM 11334569
human SKOV-3 ovarian cell line Proliferation assay Antiproliferative activity against human SKOV-3 ovarian cell line, IC50=0.72 μM 10498216
human MCF-7 breast cell line Proliferation assay Antiproliferative activity against human MCF-7 breast cell line, IC50=0.37 μM 10498216
human DU145 prostate cell line Proliferation assay Antiproliferative activity against human DU145 prostate cell line, IC50=13 nM 10498216
H460 Cytotoxicity assay Cytotoxicity against human H460 cells, IC50 = 0.22 μM. 18434153
A549 Cytotoxicity assay Cytotoxicity against human A549 cells by SRB method, IC50 = 0.08 μM. 18986807
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells by SRB method, IC50 = 0.12 μM. 18986807
A549/ATCC Antitumor assay Antitumor activity against human A549/ATCC cells by SRB method, IC50 = 0.088 μM. 19541483
HT-29 Antitumor assay Antitumor activity against human HT-29 cells by SRB method, IC50 = 0.17 μM. 19541483
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells, IC50 = 0.0059 μM. 21470864
A549 Cytotoxicity assay Cytotoxicity against human A549 cells, IC50 = 0.047 μM. 21470864
DU145 Cytotoxicity assay Cytotoxicity against human DU145 cells, IC50 = 0.03 μM. 23578545
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells, IC50 = 0.03 μM. 23578545
L1210 Cytotoxicity assay Cytotoxicity against mouse L1210 cells, IC50 = 0.04 μM. 23578545
HCT116 Cytotoxicity assay Cytotoxicity against human HCT116 cells, IC50 = 0.166 μM. 24529870
MDA-MB-231 Cytotoxicity assay Cytotoxicity against human MDA-MB-231 cells, IC50 = 0.176 μM. 24529870
A549 Cytotoxicity assay Cytotoxicity against human A549 cells, IC50 = 0.259 μM. 24529870
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
点击查看更多细胞系数据

生物活性

产品描述 SN-38 (NK012)是CPT-11的一种活性代谢物,抑制DNA topoisomerase I,DNA合成,并造成频繁的DNA单链断裂。SN-38 可诱导自噬。
靶点
Topo I [1]
(Cell-free assay)
体外研究(In Vitro)
体外研究活性

SN-38是伊立替康盐酸盐(CPT-11)的生物活性代谢物。SN-38引起DNA拓扑异构酶I的抑制最强,其次是CPT,然后是CPT-11。 CPT-11剂量依赖性地转移宽松的DNA在切口的DNA的方向上的位置,但SN-38和CPT对宽松的DNA的位置没有影响。SN-38的剂量依赖性和时间依赖性地抑制DNA的合成。 SN-38的各自的IC50值,在DNA合成是0.077微米。SN-38的细胞RNA合成的抑制作用小于对DNA合成和它不抑制蛋白质的合成。 SN-38对P388细胞造成频繁的DNA单链断裂。[1]

激酶实验 拓扑异构酶I检测
一个单位(本研究的条件下,使0.5微克SV40 DNA完全松弛的最小量)拓扑异构酶I, 0.5微升的测试化合物,和0.5μg SV40的DNA按顺序加入反应缓冲液中,它是由25毫摩尔Tris -盐酸(pH值7.5),50 mM的KCl, 5 mM的氯化镁,0.25毫摩尔EDTA二钠盐,0.25 mM二硫苏糖醇,15 μg/毫升牛血清白蛋白和5 %的甘油。然后,将反应混合物(50 μL)在37 ℃温育10分钟,并将该反应通过7.5 μL 溶液在37 ℃温育30分钟终止, 1%十二烷基硫酸钠, 20 mM的EDTA二钠盐,和0.5 mg/mL 蛋白酶K。 样品和5 μL 的上样缓冲液混合,上样缓冲液包含10 mM磷酸氢二钠,31.3%蔗糖,0.3%溴酚蓝。松弛(Ir形式)的DNA从超螺旋(形式I)中分离,带切口的( II型)的DNA通过电泳在0.8%琼脂糖凝胶分离,电泳是在在2 μg/mL CHQ, 10 mM EDTA, 30 mM 磷酸氢二钠存在下在50毫安和20 V条件下进行17小时。电泳后,将凝胶用0.05%溴化乙锭染色并用UV光(302纳米)拍摄。 DNA量是用密度计进行定量。
细胞实验 细胞系 A-172, U-87和LA-567
浓度 0 -1000 nM
孵育时间 48 小时
方法

MTT 检测

实验图片 检测方法 检测指标 实验图片 PMID
Western blot p-Chk1 / Chk1 / Topo I 18509065
Growth inhibition assay Cell viability 25759163
体内研究(In Vivo)
体内研究活性

口服给药后,SN-38的最高浓度出现在1小时后,并且未结合的SN-38内酯在小鼠血浆在1000纳克/毫升时百分比是3.4 +/- 0.67%,而在100纳克/毫升的未结合的百分比是1.18 +/- 0.14%。在含人类神经母细胞瘤的裸鼠中SN-38内酯的AUC大于在非肿瘤息动物的量。

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06143774 Recruiting
Advanced Solid Tumor
TaiRx Inc.
October 31 2023 Phase 1
NCT05101096 Recruiting
Advanced Solid Tumor|Metastatic Triple-Negative Breast Cancer|HR+/HER2- Metastatic Breast Cancer|Metastatic Urothelial Cancer
Gilead Sciences
October 20 2021 Phase 1|Phase 2
NCT05119907 Recruiting
Solid Tumor
Gilead Sciences
October 12 2021 Phase 2
NCT04866641 Recruiting
Advanced Solid Tumor
Taivex Therapeutics Corporation
June 24 2021 Phase 1
NCT04617522 Recruiting
Advanced or Metastatic Solid Tumor|Liver Failure
Gilead Sciences
April 6 2021 Phase 1

化学信息&溶解度

分子量 392.4 分子式

C22H20N2O5

CAS号 86639-52-3 SDF Download SN-38 SDF
Smiles CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)O
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 50 mg/mL ( (127.42 mM) Warmed with 50°C water bath; Ultrasonicated; ;DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

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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