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 NUHrSoszWHKxbHnm[ZJifGmxbjDhd5NigQ>? MnHzOkBl[Xm| MVzBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFCFNjDj[YxteyClYYLyfYlv\yCyUlOgZYZ1\XJiNjDkZZl{NCCLQ{WwQVAvPDNibl2= MmLWNVkzPTR6NEO=
human HCT116 cells MWHQdo9tcW[ncnH0bY9vKGG|c3H5 MmjoN{Bl[Xm| MXHBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEGxOkBk\WyuczDh[pRmeiB|IHThfZMtKEmFNUC9NE42PSCwTR?= M3G3SFE6OjV2OESz
human PC3 cells M1LKTWN6fG:2b4jpZ:Kh[XO|YYm= MlP4O|IhcA>? MoLSR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVGM{KGOnbHzzJIV5eHKnc4Ppcoch[WyyaHG1ZoV1[TNiaX70[YdzcW5iYYPz[ZN{\WRiYYOgZ4VtdCC|dYL2bZZidCCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwQVIvPiCwTR?= NH;mSZUzOjl3OUK0Oi=>
human A549 cells MV\DfZRwfG:6aXRCpIF{e2G7 Mo\XN{Bl[Xm| MWLDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGGodHXyJFMh\GG7czDifUBUWkJiYYPzZZktKEmFNUC9Nk44OiCwTR?= NUjiOVBSOjR3Mkm4O|A>
human QG56 cells NVnLNWJmWHKxbHnm[ZJifGmxbjDhd5NigQ>? MX[zJIRigXN? MXzBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFGJNU[gZ4VtdHNiYX\0[ZIhOyCmYYnzMEBKSzVyPUKuPEBvVQ>? MoHlNVkzPTR6NEO=
human NCI-H460 cells MYTQdo9tcW[ncnH0bY9vKGG|c3H5 M3PGblMh\GG7cx?= NUTuOHdESW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDR4MDDj[YxteyCjZoTldkA{KGSjeYOsJGlEPTB;Mz6zJI5O MlfENVkzPTR6NEO=
human DU145 cells M1iwNnBzd2yrZnXyZZRqd25iYYPzZZk> NYP0XHFWQTZiaB?= NYO2TWxzSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDEWVE1PSClZXzsd{Bi\nSncjC5OkBpenNuIFnDOVA:PCCwTR?= NEX2OIoyQDJ5NkG0NS=>
human breast cancer cell line (SK-BR-3) NXHaUVVlS3m2b4TvfIlkyqCjc4PhfS=> NHnmXXpKdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIwhdGmwZTCoV2suSlJvMzmsJGlEPTB;NDDuUS=> M{jm[lEyOzN2NU[5
human KB3-1 cells NWPHNlN[S3m2b4TvfIlkyqCjc4PhfS=> MmXHOEBl[Xm| M4LzRmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtDOy1zIHPlcIx{KGGodHXyJFQh\GG7czDifUBOXFRibXX0bI9lNCCLQ{WwQVQhdk1? NVv6do1NOTl|MEOzNFY>
human HCT116 cells M2nNNGN6fG:2b4jpZ:Kh[XO|YYm= NIj3UG04OiCq M4KycmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhEXDFzNjDj[YxteyCjZoTldkA4OiCqcoOgZpkhe3WuZn;ybI9l[W2rbnWgRkBie3OjeTygTWM2OD12LkK4JI5O NWDJRoxuOjV6M{WzOVk>
MDA-MB-435 S human breast cancer cells NYDPdFBkTnWwY4Tpc44h[XO|YYm= MnTkTY5pcWKrdHnvckBi\2GrboP0JG1FSS2PQj20N|UhWyCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIx{KGmwIITo[UBi[nOnbnPlJI9nKGGuYoXtbY4tKEmFNUC9OUBvVQ>? NF;jd|kyOTB3MkiwNi=>
human HT-29 cells NXfUcZNZS3m2b4TvfIlkyqCjc4PhfS=> MoPyR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTHQuOjliY3XscJMtKEmFNUC9OU46KG6P MYWyNVQ4ODh4NB?=
human lung cancer cell line (H128) MlfuR5l1d3SxeHnjxsBie3OjeR?= M3TiPGlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJIx2dmdiY3HuZ4VzKGOnbHygcIlv\SBqSEGyPEktKEmFNUC9OkBvVQ>? NX61e5N{OTF|M{S1Olk>
human MIA PaCa cells MnjNVJJwdGmoZYLheIlwdiCjc4PhfS=> MYLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2LQTDQZWNiKGOnbHzzJIFnfGW{IEm2JIhzeyxiSVO1NF03KG6P Mo\sNVgzPzZzNEG=
human HCT116 colon cancer cell line NFzPe2FHfW6ldHnvckBie3OjeR?= M1zMUWlvcGmkaYTvdpkh[2:wY3XueJJifGmxbjDh[4FqdnO2IHj1cYFvKEiFVEGxOkBkd2yxbjDjZY5k\XJiY3XscEBtcW6nLDDJR|UxRTdibl2= M2XNSlE2QDB6NEW2
human stomach cancer cell line (MKN45) NXzqN|A1S3m2b4TvfIlkyqCjc4PhfS=> MX7JckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDzeI9u[WOqIHPhcoNmeiClZXzsJIxqdmViKF3LUlQ2MSxiSVO1NF05KG6P MXSxNVM{PDV4OR?=
human A2780 cells MYPDfZRwfG:6aXRCpIF{e2G7 NVLLSmJ4PzJiaB?= M3;SbGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGEzPzhyIHPlcIx{KG:4ZYLlfJBz\XO|aX7nJIFteGijNXLleIE{KGmwdHXndolvKGG|c3Xzd4VlKGG|IHPlcIwhe3W{dnn2ZYwh[W[2ZYKgO|IhcHK|IHL5JHNTSiCjc4PhfUwhUUN3ME25JI5O NH[4VZozOjl3OUK0Oi=>
human ovarian cancer cell line (SK-OV-3) MmXCR5l1d3SxeHnjxsBie3OjeR?= MlXzTY4hXmm2cn:gZ5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gc5ZiemmjbjDjZY5k\XJiY3XscEBtcW6nIDjTT{1QXi1|KTygTWM2OD1zMTDuUS=> MkKzNVE{OzR3Nkm=
human DU145 prostate cell line NILNZ4xRem:uaX\ldoF1cW:wIHHzd4F6 MnvRRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCGVUG0OUBxem:|dHH0[UBk\WyuIHzpcoUtKEmFNUC9NVMhdk1? Mon5NVA1QTh{MU[=
human colon cancer cell line (WiDr) M1TubGN6fG:2b4jpZ:Kh[XO|YYm= M1[1N2lvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJINwdG:wIHPhcoNmeiClZXzsJIxqdmViKGfpSJIqNCCLQ{WwQVE1KG6P M1HmT|EyOzN2NU[5
human lung cancer cell line (A549) MVXDfZRwfG:6aXRCpIF{e2G7 NIP2W2hKdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBtfW6pIHPhcoNmeiClZXzsJIxqdmViKFG1OFkq NELzdJUyOTN|NEW2PS=>
human tumor HL60 cell-line MXfGeY5kfGmxbjDhd5NigQ>? NVzqe|BtOyCmYYnz MkLuTY4ufmm2cn:gbY5pcWKrdH;yfUBkd26lZX70doF1cW:wIH\vdkBpfW2jbjD0eY1weiCKTE[wJINmdGxvbHnu[UB4[XNiZHX0[ZJucW6nZDD1d4lv\yCVUlKgZZN{[XliYX\0[ZIhOyCmYYnzJI9nKGmwY4XiZZRqd25uIFnDOVA:OTlibl2= NETzc20yPTlzM{m5Oi=>
PC-3 carcinoma cell line M4j6Xmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFjMXIxEd26lZX70doF1cW:wIILldZVqemWmIITvJIlvcGmkaYSg[5Jwf3SqIH;mJIh2dWGwIIDyc5N1[XSnIGDDMVMh[2G{Y3nuc41iKGOnbHygcIlv\SxiSVO1NF0{PS54IH7N MUOxOVQ2PDJ|MB?=
human KBV1 cells MlT6R5l1d3SxeHnjxsBie3OjeR?= NIKxXYQ1KGSjeYO= M{\1VWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KE2GUkGgc5ZmemW6cILld5NqdmdiaIXtZY4hU0KYMTDj[YxteyCjZoTldkA1KGSjeYOgZpkhVVSWIH3leIhw\CxiSVO1NF01PiCwTR?= NWDKdGJsOTl|MEOzNFY>
human A549 cells MYfDfZRwfG:6aXRCpIF{e2G7 MnXrR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVU1QSClZXzsd{whUUN3ME20O{BvVQ>? NVrlRXRuOjF2N{C4OlQ>
NSCLC-H460 NIe3U5FEgXSxdH;4bYPDqGG|c3H5 MXHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDuc44ue22jbHytZ4VtdCCudX7nJINiemOrbn;tZUBk\WyuIHzpcoUhUDR4MDCoUnNEVENvSES2NEktKEmFNUC9PFAhdk1? MUexNVU3Ozl{NR?=
MDA-MB-435 S human breast cancer cells NVrv[WJQTnWwY4Tpc44h[XO|YYm= M1;5fGlvcGmkaYTpc44h[WejaX7zeEBOTEFvTVKtOFM2KFNiaIXtZY4h[nKnYYP0JINidmOncjDj[YxteyCrbjD0bIUheHKnc3XuZ4Uhd2ZiM{CgcYcwdUxiSGPBMEBKSzVyPUWwJI5O NHXmPGwyOTB3MkiwNi=>
human H460 cell M1\HcGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NXjKSIt6UW6qaXLpeIlwdiCxZjDoeY1idiCKNE[wJINmdGxiZ4Lve5RpNCCLQ{WwQVgxKG6P MmLUNVY6OTN5ME[=
human MDA-MB-231 cells NVzPSIlNS3m2b4TvfIlkyqCjc4PhfS=> NXLDTXlwS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUSDLV3CMVI{OSClZXzsd{whUUN3ME2xO|Yhdk1? M3zMPFI1PTJ7OEew
human KBH5.0 cells MWnDfZRwfG:6aXRCpIF{e2G7 NInEWoE1KGSjeYO= MoT4R5l1d3SxeHnjbZR6KGGpYXnud5QhSkOUUDDveoVz\XiycnXzd4lv\yCqdX3hckBMSkh3LkCgZ4VtdHNiYX\0[ZIhPCCmYYnzJIJ6KE2WVDDt[ZRpd2RuIFnDOVA:OC5|IN88US=> NGXpPZIyQTNyM{OwOi=>
human MCF-7 breast cell line NXKwNIxJWHKxbHnm[ZJifGmxbjDhd5NigQ>? NGC4dFVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3DSk04KGK{ZXHzeEBk\WyuIHzpcoUtKEmFNUC9NE4{PyEQvF2= NGLQNpMyODR7OEKxOi=>
human SKOV-3 ovarian cell line NV3abIRLWHKxbHnm[ZJifGmxbjDhd5NigQ>? MVLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFONT2[tN{BwfmG{aXHuJINmdGxibHnu[UwhUUN3ME2wMlczKM7:TR?= NI\te4UyODR7OEKxOi=>
human Bel-7402 liver cancer cell line MWDGeY5kfGmxbjDhd5NigQ>? NF:1SnpKdmirYnn0c5J6KGOxbnPlcpRz[XSrb36gZYdicW6|dDDoeY1idiCEZXytO|QxOiCuaY\ldkBk[W6lZYKgZ4VtdCCuaX7lMEBKSzVyPUOuNVkh|ryP NFPte|QyPThyOES1Oi=>
HEK293 cells NWThWndJS3m2b4TvfIlkyqCjc4PhfS=> NEPX[3M4OiCq NYPPfIZ6UW62cnnud4lkKGO7dH;0c5hq[2m2eTDh[4FqdnO2IFjFT|I6OyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigQ>? MkLsNlUzPzJyNUW=

... 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

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Topoisomerase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID