SN-38

Catalog No.S4908

SN-38 Chemical Structure

Molecular Weight(MW): 392.4

SN-38 is an active metabolite of CPT-11, inhibits DNA topoisomerase I, DNA synthesis and causes frequent DNA single-strand breaks.

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  • (B) HCT116 cells were treated with increasing doses of SN-38 and treated with 4 nM SN-38 for different time. Cell extracts were prepared and analyzed by Western blotting with indicated antibody. These experiments were repeated thrice. (C) HCT116 cells were transfected with 2 μg of EGFP-LC3 construct. At 8 h post-transfection, cells were treated with 4 nM of SN-38 for 48 h. And then cells were examined by confocal microscopy (magnification × 400). The percentage of cells showing accumulation of EGFP-LC3 in puncta (EGFP-LC3vac) was quantified. (D) LOVO and HCT116 cells were treated with 2 nM and 4 nM of SN-38 combined with 10 mM of 3-Methyladenine (3-MA) for 48 h respectively. Cell extracts were prepared and analyzed by Western blotting with indicated antibody. These experiments were repeated thrice. (E) Cells were treated with indicated concentrations of 3-MA and SN-38 for 48 h. Cell apoptosis was assessed by Annexin V-FITC/PI staining assay by flow cytometry. Columns, means of three determinations; bars, SD. (F) and (G) LOVO and HCT116 cells were transfected with 50 nM of NC siRNA, ATG5 siRNA respectively, and then were treated with increasing doses of SN-38 for 48 h, the knockdown effects on ATG5 were confirmed by Western blot analysis (upper panel). Cell viability was measured using CCK8 assay. Columns, means of three determinations; bars, SD.

    Free Radic Biol Med, 2017, 104:280-297. SN-38 purchased from Selleck.

    HCT116 cells were pretreated with tested compounds for 1 hour and then cotreated with 1 μM SN-38 for 2 hours. Cell lysates were then subjected to Western blot analysis. Data shown are representative of three independent experiments. Con, concentration.

    J Pharmacol Exp Ther 2014 348(3), 432-41. SN-38 purchased from Selleck.

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Biological Activity

Description SN-38 is an active metabolite of CPT-11, inhibits DNA topoisomerase I, DNA synthesis and causes frequent DNA single-strand breaks.
Targets
Topo I [1]
(Cell-free assay)
In vitro

SN-38, a biological active metabolite of irinotecan hydrochloride (CPT-11). SN-38 causes the strongest inhibition of DNA topoisomerase I, followed by CPT and then CPT-11. CPT-11 dose dependently shifts the position of relaxed DNA in the direction of nicked DNA, but SN-38 and CPT shows no effect on the position of relaxed DNA. SN-38 dose-dependently and time-dependently inhibit DNA synthesis. Respective IC50 values of SN-38, in DNA synthesis is 0.077 μM. The inhibitory effect of SN-38 on RNA synthesis is less than that on DNA synthesis and it does not inhibit protein synthesis. SN-38 caused frequent DNA single-strand breaks in P388 cells. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human PC6 cells MWLQdo9tcW[ncnH0bY9vKGG|c3H5 MWK2JIRigXN? NWf3bndjSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDQR|Yh[2WubIOgZ4FzenmrbnegdHJEKGGodHXyJFYh\GG7czygTWM2OD1yLkSzJI5O NXnQUHFKOTl{NUS4OFM>
human HCT116 cells NFfjToNRem:uaX\ldoF1cW:wIHHzd4F6 NYXyU|g6OyCmYYnz NXHrb5ROSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgN{Bl[Xm|LDDJR|UxRTBwNUWgcm0> MmD1NVkzPTR6NEO=
human PC3 cells NYXRVndMS3m2b4TvfIlkyqCjc4PhfS=> NIXPcXM4OiCq NX64V4JmS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWEN|IHPlcIx{KGW6cILld5NqdmdiYXzwbIE2[mW2YUOgbY51\We{aX6gZZN{\XO|ZXSgZZMh[2WubDDzeZJ3cX[jbDDh[pRmeiB5MjDodpMh[nliU2LCJIF{e2G7LDDJR|UxRTJwNjDuUS=> MnHpNlI6PTl{NE[=
human A549 cells MlrUR5l1d3SxeHnjxsBie3OjeR?= M2LKO|Mh\GG7cx?= NFXpcIZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDNiZHH5d{BjgSCVUlKgZZN{[XluIFnDOVA:Oi55MjDuUS=> MUKyOFUzQTh5MB?=
human QG56 cells M4XGOHBzd2yrZnXyZZRqd25iYYPzZZk> MoXVN{Bl[Xm| NUflZ5J2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDRS|U3KGOnbHzzJIFnfGW{IEOg[IF6eyxiSVO1NF0zNjhibl2= NIrJNZcyQTJ3NEi0Ny=>
human NCI-H460 cells MkX3VJJwdGmoZYLheIlwdiCjc4PhfS=> MVuzJIRigXN? NXPScHF2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDR4MDDj[YxteyCjZoTldkA{KGSjeYOsJGlEPTB;Mz6zJI5O MUmxPVI2PDh2Mx?=
human DU145 cells MYXQdo9tcW[ncnH0bY9vKGG|c3H5 NFL0O|M6PiCq MmmxRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCGVUG0OUBk\WyuczDh[pRmeiB7NjDodpMtKEmFNUC9OEBvVQ>? M2nmW|E5Ojd4MUSx
human breast cancer cell line (SK-BR-3) NIi3TZZEgXSxdH;4bYPDqGG|c3H5 NUfTUYZNUW5iVnn0do8h[3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4h[nKnYYP0JINidmOncjDj[YxtKGyrbnWgLHNMNUKULUOpMEBKSzVyPUSgcm0> MXuxNVM{PDV4OR?=
human KB3-1 cells NF7YPHNEgXSxdH;4bYPDqGG|c3H5 NWTKOmxYPCCmYYnz NW[3XWpKS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU0J|LUGgZ4VtdHNiYX\0[ZIhPCCmYYnzJIJ6KE2WVDDt[ZRpd2RuIFnDOVA:PCCwTR?= NXi1XVh4OTl|MEOzNFY>
human HCT116 cells NIW5V29EgXSxdH;4bYPDqGG|c3H5 MoPlO|IhcA>? Ml7qR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGNVOTF4IHPlcIx{KGGodHXyJFczKGi{czDifUB{fWyob4Loc4RidWmwZTDCJIF{e2G7LDDJR|UxRTRwMkigcm0> NFLQXXczPTh|NUO1PS=>
MDA-MB-435 S human breast cancer cells Mo\jSpVv[3Srb36gZZN{[Xl? MXfJcohq[mm2aX;uJIFo[Wmwc4SgUWRCNU2ELUSzOUBUKGi3bXHuJIJz\WG|dDDjZY5k\XJiY3XscJMhcW5idHjlJIFje2WwY3Wgc4Yh[WykdX3pckwhUUN3ME21JI5O NHHPVFUyOTB3MkiwNi=>
human HT-29 cells MWDDfZRwfG:6aXRCpIF{e2G7 M4fYN2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhVNTJ7IHPlcIx{NCCLQ{WwQVUvQSCwTR?= NGfLd3QzOTR5MEi2OC=>
human lung cancer cell line (H128) MmnOR5l1d3SxeHnjxsBie3OjeR?= NFXyTndKdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBtfW6pIHPhcoNmeiClZXzsJIxqdmViKFixNlgqNCCLQ{WwQVYhdk1? MWCxNVM{PDV4OR?=
human MIA PaCa cells M4n0Z3Bzd2yrZnXyZZRqd25iYYPzZZk> MULBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2LQTDQZWNiKGOnbHzzJIFnfGW{IEm2JIhzeyxiSVO1NF03KG6P NIG0[VAyQDJ5NkG0NS=>
human HCT116 colon cancer cell line MVzGeY5kfGmxbjDhd5NigQ>? Mnv6TY5pcWKrdH;yfUBkd26lZX70doF1cW:wIHHnZYlve3RiaIXtZY4hUEOWMUG2JINwdG:wIHPhcoNmeiClZXzsJIxqdmVuIFnDOVA:PyCwTR?= NUHmcpNOOTV6MEi0OVY>
human stomach cancer cell line (MKN45) MV3DfZRwfG:6aXRCpIF{e2G7 M3;FbGlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJJN1d22jY3igZ4Fv[2W{IHPlcIwhdGmwZTCoUWtPPDVrLDDJR|UxRThibl2= NGrWfHIyOTN|NEW2PS=>
human A2780 cells NY\wRpd2S3m2b4TvfIlkyqCjc4PhfS=> M{jTWVczKGh? M{XRZWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGEzPzhyIHPlcIx{KG:4ZYLlfJBz\XO|aX7nJIFteGijNXLleIE{KGmwdHXndolvKGG|c3Xzd4VlKGG|IHPlcIwhe3W{dnn2ZYwh[W[2ZYKgO|IhcHK|IHL5JHNTSiCjc4PhfUwhUUN3ME25JI5O Moq1NlI6PTl{NE[=
human ovarian cancer cell line (SK-OV-3) MW\DfZRwfG:6aXRCpIF{e2G7 M{nJTGlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJI93[XKrYX6gZ4Fv[2W{IHPlcIwhdGmwZTCoV2suV1ZvMzmsJGlEPTB;MUGgcm0> NGDybJAyOTN|NEW2PS=>
human DU145 prostate cell line NWmxTot6WHKxbHnm[ZJifGmxbjDhd5NigQ>? MY\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKESXMUS1JJBzd3O2YYTlJINmdGxibHnu[UwhUUN3ME2xN{BvVQ>? NW\qOWF3OTB2OUiyNVY>
human colon cancer cell line (WiDr) NFnpWZNEgXSxdH;4bYPDqGG|c3H5 MnvhTY4hXmm2cn:gZ5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gZ49td25iY3HuZ4VzKGOnbHygcIlv\SBqV3nEdkktKEmFNUC9NVQhdk1? NXXmW3VQOTF|M{S1Olk>
human lung cancer cell line (A549) MXHDfZRwfG:6aXRCpIF{e2G7 MYHJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDseY5oKGOjbnPldkBk\WyuIHzpcoUhMEF3NEmp MXuxNVM{PDV4OR?=
human tumor HL60 cell-line MnG2SpVv[3Srb36gZZN{[Xl? M{jMNVMh\GG7cx?= NGOw[ZBKdi24aYTyc{BqdmirYnn0c5J6KGOxbnPlcpRz[XSrb36g[o9zKGi3bXHuJJR2dW:{IFjMOlAh[2WubD3sbY5mKHejczDk[ZRmem2rbnXkJJV{cW6pIGPSRkBie3OjeTDh[pRmeiB|IHThfZMhd2ZiaX7jeYJifGmxbjygTWM2OD1zOTDuUS=> Mn;iNVU6OTN7OU[=
PC-3 carcinoma cell line MnG4S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MVjDc45k\W62cnH0bY9vKHKncYXpdoVlKHSxIHnubIljcXRiZ4Lve5RpKG:oIHj1cYFvKHC{b4P0ZZRmKFCFLUOgZ4Fz[2mwb33hJINmdGxibHnu[UwhUUN3ME2zOU43KG6P MnrGNVU1PTR{M{C=
human KBV1 cells MWfDfZRwfG:6aXRCpIF{e2G7 MUS0JIRigXN? NV32NItrS3m2b4TvfIlkcXS7IHHnZYlve3RiTVTSNUBwfmW{ZYjwdoV{e2mwZzDoeY1idiCNQm[xJINmdGy|IHHmeIVzKDRiZHH5d{BjgSCPVGSgcYV1cG:mLDDJR|UxRTR4IH7N M3P0[VE6OzB|M{C2
human A549 cells MkK4R5l1d3SxeHnjxsBie3OjeR?= NEXMPVhEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{NCCLQ{WwQVQ4KG6P MnPvNlE1PzB6NkS=
NSCLC-H460 Ml\0R5l1d3SxeHnjxsBie3OjeR?= MmXWR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gco9vNXOvYXzsMYNmdGxibIXu[{Bk[XKlaX7vcYEh[2WubDDsbY5mKEh2NkCgLG5US0yFLVi0OlAqNCCLQ{WwQVgxKG6P NGfxbYcyOTV4M{myOS=>
MDA-MB-435 S human breast cancer cells MnjmSpVv[3Srb36gZZN{[Xl? MmjRTY5pcWKrdHnvckBi\2GrboP0JG1FSS2PQj20N|UhWyCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIx{KGmwIITo[UBxemW|ZX7j[UBw\iB|MDDt[{9uVCCKU1GsJGlEPTB;NUCgcm0> NFz3Z2QyOTB3MkiwNi=>
human H460 cell NFfWVJZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= Moe4TY5pcWKrdHnvckBw\iCqdX3hckBJPDZyIHPlcIwh\3Kxd4ToMEBKSzVyPUiwJI5O M2ju[FE3QTF|N{C2
human MDA-MB-231 cells M1O5Z2N6fG:2b4jpZ:Kh[XO|YYm= NG\YUYdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOTEFvTVKtNlMyKGOnbHzzMEBKSzVyPUG3OkBvVQ>? MknnNlQ2Ojl6N{C=
human KBH5.0 cells NF\ZO|JEgXSxdH;4bYPDqGG|c3H5 M{TJRVQh\GG7cx?= M{TCSmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KEKFUmCgc5ZmemW6cILld5NqdmdiaIXtZY4hU0KKNT6wJINmdGy|IHHmeIVzKDRiZHH5d{BjgSCPVGSgcYV1cG:mLDDJR|UxRTBwMzFOwG0> NEOxdVUyQTNyM{OwOi=>
human MCF-7 breast cell line MmTIVJJwdGmoZYLheIlwdiCjc4PhfS=> NFz6b|ZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3DSk04KGK{ZXHzeEBk\WyuIHzpcoUtKEmFNUC9NE4{PyEQvF2= NEK1TXAyODR7OEKxOi=>
human SKOV-3 ovarian cell line NEPS[GRRem:uaX\ldoF1cW:wIHHzd4F6 NXTXPVlTSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTT29XNTNib4\hdolidiClZXzsJIxqdmVuIFnDOVA:OC55MjFOwG0> MXKxNFQ6QDJzNh?=
human Bel-7402 liver cancer cell line MkPVSpVv[3Srb36gZZN{[Xl? NXnPUoEzUW6qaXLpeI9zgSClb37j[Y51emG2aX;uJIFo[Wmwc4SgbJVu[W5iQnXsMVc1ODJibHn2[ZIh[2GwY3XyJINmdGxibHnu[UwhUUN3ME2zMlE6KM7:TR?= NGTNUnoyPThyOES1Oi=>
HEK293 cells NWntcWpJS3m2b4TvfIlkyqCjc4PhfS=> MnXKO|IhcA>? MUjJcpRzcW6|aXOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhUEWNMkmzJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5 Mme5NlUzPzJyNUW=

... Click to View More Cell Line Experimental Data

In vivo After oral dosing, peak SN-38 concentrations occurrs within 1 h, and the The percent unbound SN-38 lactone in murine plasma at 1000 ng/mL is 3.4 +/- 0.67%, whereas at 100 ng/mL the percent unbound is 1.18 +/- 0.14%. SN-38 lactone AUCs in micebearing human neuroblastoma xenografts are greater than in nontumor-bearing animals. [2]

Protocol

Kinase Assay:[1]
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Topoisomerase I Assay:

One unit (the minimum amount for full relaxation of 0.5 μg SV40 DNA under the conditions of this study) of topoisomerase I, 0.5 μL of the test compounds, and 0.5μg SV40 DNA are added sequentially to the reaction buffer, which is composed of 25 mM Tris-HCl (pH 7.5), 50 mM KC1, 5 mM MgCl2, 0.25 mM EDTA disodium salt, 0.25 mM dithiothreitol, 15μg /mL bovine serum albumin, and 5% glycerol. Then, the reaction mixture (50 μL) is incubated for 10 min at 37 °C, and the reaction is terminated by treatment with 7.5 μL of a solution consisting of 1% sodium dodecyl sulfate, 20 mM EDTA disodium salt, and 0.5 mg/mL proteinase K for an additional 30 min at 37°C. The samples are mixed with 5 μL of the loading buffer containing 10 mM Na2HPO4, 31.3% sucrose, and 0.3% bromophenol blue. Relaxed (form Ir) DNA is separated from supercoiled (form I) and nicked (form II) DNA by electrophoresis on 0.8% agarose gel at 50 mA and 20 V for 17 h in the presence of 2 μg/mL chloroquine, 10 mM EDTA, 30 mM NaH2PO4, and 36 Mm Tris-HCl (pH 7.8). After electrophoresis, the gel is stained with 0.05% ethidium bromide and photographed with UV light (302 nm). The amount of DNA is quantified using a densitometer.
Cell Research:[3]
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  • Cell lines: A-172, U-87, and LA-567
  • Concentrations: 0 -1000 nM
  • Incubation Time: 48 h
  • Method: MTT assay
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 21 mg/mL (53.51 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 392.4
Formula

C22H20N2O5

CAS No. 86639-52-3
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00311610 Completed Colorectal Cancer Alliance for Clinical Trials in Oncology|National Cancer Institute (NCI) January 2006 Phase 2
NCT00046540 Completed Neoplasms INSYS Therapeutics Inc October 2002 Phase 1
NCT00104754 Withdrawn Lung Cancer Alliance for Clinical Trials in Oncology|National Cancer Institute (NCI) null Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Topoisomerase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID