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 NWTscVd[WHKxbHnm[ZJifGmxbjDhd5NigQ>? MYq2JIRigXN? NXnlcFc1SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDQR|Yh[2WubIOgZ4FzenmrbnegdHJEKGGodHXyJFYh\GG7czygTWM2OD1yLkSzJI5O MlnSNVkzPTR6NEO=
human HCT116 cells MmP5VJJwdGmoZYLheIlwdiCjc4PhfS=> NYHtc2E2OyCmYYnz MmLvRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKQ2SxNVYh[2WubIOgZYZ1\XJiMzDkZZl{NCCLQ{WwQVAvPTVibl2= NUS5TXgxOTl{NUS4OFM>
human PC3 cells NELJW3dEgXSxdH;4bYPDqGG|c3H5 NW[1NnRyPzJiaB?= MV\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDQR|Mh[2WubIOg[ZhxemW|c3nu[{BidHCqYUXi[ZRiOyCrboTl[5JqdiCjc4Pld5Nm\CCjczDj[YxtKHO3co\peoFtKGGodHXyJFczKGi{czDifUBUWkJiYYPzZZktKEmFNUC9Nk43KG6P MYqyNlk2QTJ2Nh?=
human A549 cells M1;NRWN6fG:2b4jpZ:Kh[XO|YYm= Ml\5N{Bl[Xm| MWTDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGGodHXyJFMh\GG7czDifUBUWkJiYYPzZZktKEmFNUC9Nk44OiCwTR?= MVOyOFUzQTh5MB?=
human QG56 cells NF[0S4NRem:uaX\ldoF1cW:wIHHzd4F6 NGn6ZXQ{KGSjeYO= NEPnNZlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGHHOVYh[2WubIOgZYZ1\XJiMzDkZZl{NCCLQ{WwQVIvQCCwTR?= M3LrNlE6OjV2OESz
human NCI-H460 cells NHzBdHVRem:uaX\ldoF1cW:wIHHzd4F6 M2nRcVMh\GG7cx?= MnLaRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCQQ1mtTFQ3OCClZXzsd{Bi\nSncjCzJIRigXNuIFnDOVA:Oy5|IH7N MkjSNVkzPTR6NEO=
human DU145 cells MXLQdo9tcW[ncnH0bY9vKGG|c3H5 MWK5OkBp NVWzPGRYSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDEWVE1PSClZXzsd{Bi\nSncjC5OkBpenNuIFnDOVA:PCCwTR?= MnHLNVgzPzZzNEG=
human breast cancer cell line (SK-BR-3) NVfJV3VjS3m2b4TvfIlkyqCjc4PhfS=> MYnJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDidoVie3RiY3HuZ4VzKGOnbHygcIlv\SBqU1utRnIuOyluIFnDOVA:PCCwTR?= MkHSNVE{OzR3Nkm=
human KB3-1 cells MW\DfZRwfG:6aXRCpIF{e2G7 MVW0JIRigXN? M176PGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtDOy1zIHPlcIx{KGGodHXyJFQh\GG7czDifUBOXFRibXX0bI9lNCCLQ{WwQVQhdk1? MUWxPVMxOzNyNh?=
human HCT116 cells MnewR5l1d3SxeHnjxsBie3OjeR?= M4XjVVczKGh? M3vBOWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhEXDFzNjDj[YxteyCjZoTldkA4OiCqcoOgZpkhe3WuZn;ybI9l[W2rbnWgRkBie3OjeTygTWM2OD12LkK4JI5O MYCyOVg{PTN3OR?=
MDA-MB-435 S human breast cancer cells NFjKUVRHfW6ldHnvckBie3OjeR?= Ml71TY5pcWKrdHnvckBi\2GrboP0JG1FSS2PQj20N|UhWyCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIx{KGmwIITo[UBi[nOnbnPlJI9nKGGuYoXtbY4tKEmFNUC9OUBvVQ>? M{SzdFEyODV{OECy
human HT-29 cells NGDkb4xEgXSxdH;4bYPDqGG|c3H5 NX7yO3VrS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUFRvMkmgZ4VtdHNuIFnDOVA:PS57IH7N MXqyNVQ4ODh4NB?=
human lung cancer cell line (H128) M1Tl[mN6fG:2b4jpZ:Kh[XO|YYm= NXHH[lNiUW5iVnn0do8h[3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hdHWwZzDjZY5k\XJiY3XscEBtcW6nIDjINVI5MSxiSVO1NF03KG6P NUSxb4Z6OTF|M{S1Olk>
human MIA PaCa cells NH;TUI5Rem:uaX\ldoF1cW:wIHHzd4F6 NF;ySIFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3JRUBR[UOjIHPlcIx{KGGodHXyJFk3KGi{czygTWM2OD14IH7N Ml\pNVgzPzZzNEG=
human HCT116 colon cancer cell line MUXGeY5kfGmxbjDhd5NigQ>? NHHXeYVKdmirYnn0c5J6KGOxbnPlcpRz[XSrb36gZYdicW6|dDDoeY1idiCKQ2SxNVYh[2:ub36gZ4Fv[2W{IHPlcIwhdGmwZTygTWM2OD15IH7N NIHqV4IyPThyOES1Oi=>
human stomach cancer cell line (MKN45) MmXjR5l1d3SxeHnjxsBie3OjeR?= MUTJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDzeI9u[WOqIHPhcoNmeiClZXzsJIxqdmViKF3LUlQ2MSxiSVO1NF05KG6P NWDJXHBqOTF|M{S1Olk>
human A2780 cells M1nXemN6fG:2b4jpZ:Kh[XO|YYm= NIXS[mk4OiCq NY\GZ4RCS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTJ5OECgZ4VtdHNib4\ldoV5eHKnc4Ppcoch[WyyaHG1ZoV1[TNiaX70[YdzcW5iYYPz[ZN{\WRiYYOgZ4VtdCC|dYL2bZZidCCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwQVkhdk1? NYjjZZpUOjJ7NUmyOFY>
human ovarian cancer cell line (SK-OV-3) MYfDfZRwfG:6aXRCpIF{e2G7 M4TwS2lvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJI93[XKrYX6gZ4Fv[2W{IHPlcIwhdGmwZTCoV2suV1ZvMzmsJGlEPTB;MUGgcm0> MWmxNVM{PDV4OR?=
human DU145 prostate cell line M33YUXBzd2yrZnXyZZRqd25iYYPzZZk> M1LSTmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iRGWxOFUheHKxc4TheIUh[2WubDDsbY5mNCCLQ{WwQVE{KG6P NX7vVFNLOTB2OUiyNVY>
human colon cancer cell line (WiDr) NW\MbZhPS3m2b4TvfIlkyqCjc4PhfS=> MUXJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDjc4xwdiClYX7j[ZIh[2WubDDsbY5mKCiZaVTyLUwhUUN3ME2xOEBvVQ>? MVmxNVM{PDV4OR?=
human lung cancer cell line (A549) NHPQ[29EgXSxdH;4bYPDqGG|c3H5 MkjCTY4hXmm2cn:gZ5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gcJVv\yClYX7j[ZIh[2WubDDsbY5mKCiDNUS5LS=> M3zQZ|EyOzN2NU[5
human tumor HL60 cell-line NIX2eYFHfW6ldHnvckBie3OjeR?= NGX1cXg{KGSjeYO= NYXkdlZtUW5vdnn0do8hcW6qaXLpeI9zgSClb37j[Y51emG2aX;uJIZweiCqdX3hckB1fW2xcjDIUFYxKGOnbHytcIlv\SC5YYOg[IV1\XKvaX7l[EB2e2mwZzDTVmIh[XO|YYmgZYZ1\XJiMzDkZZl{KG:oIHnuZ5Vj[XSrb36sJGlEPTB;MUmgcm0> Mmm0NVU6OTN7OU[=
PC-3 carcinoma cell line MkjCS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MWLDc45k\W62cnH0bY9vKHKncYXpdoVlKHSxIHnubIljcXRiZ4Lve5RpKG:oIHj1cYFvKHC{b4P0ZZRmKFCFLUOgZ4Fz[2mwb33hJINmdGxibHnu[UwhUUN3ME2zOU43KG6P M4\idFE2PDV2MkOw
human KBV1 cells NUnyR5Q3S3m2b4TvfIlkyqCjc4PhfS=> NXLkeG9oPCCmYYnz M2W3UmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KE2GUkGgc5ZmemW6cILld5NqdmdiaIXtZY4hU0KYMTDj[YxteyCjZoTldkA1KGSjeYOgZpkhVVSWIH3leIhw\CxiSVO1NF01PiCwTR?= NI\lZ3AyQTNyM{OwOi=>
human A549 cells M17YUmN6fG:2b4jpZ:Kh[XO|YYm= NV;VTVdFS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTV2OTDj[YxteyxiSVO1NF01PyCwTR?= NW\CUYp5OjF2N{C4OlQ>
NSCLC-H460 MlroR5l1d3SxeHnjxsBie3OjeR?= NE\XVnREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBvd25vc33hcIwu[2WubDDseY5oKGOjcnPpco9u[SClZXzsJIxqdmViSES2NEApVlOFTFOtTFQ3OCluIFnDOVA:QDBibl2= Mnf5NVE2PjN7MkW=
MDA-MB-435 S human breast cancer cells MWDGeY5kfGmxbjDhd5NigQ>? NYjsbJFwUW6qaXLpeIlwdiCjZ3HpcpN1KE2GQT3NRk01OzViUzDoeY1idiCkcnXhd5Qh[2GwY3XyJINmdGy|IHnuJJRp\SCycnXz[Y5k\SCxZjCzNEBu\y:vTDDIV2EtKEmFNUC9OVAhdk1? MYWxNVA2OjhyMh?=
human H460 cell M13Te2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NGq0Xo5KdmirYnn0bY9vKG:oIHj1cYFvKEh2NkCgZ4VtdCCpcn;3eIgtKEmFNUC9PFAhdk1? NYq3cGZSOTZ7MUO3NFY>
human MDA-MB-231 cells M{e4UmN6fG:2b4jpZ:Kh[XO|YYm= MXvDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy|LDDJR|UxRTF5NjDuUS=> NF;NeVgzPDV{OUi3NC=>
human KBH5.0 cells MoD5R5l1d3SxeHnjxsBie3OjeR?= NFG0PGk1KGSjeYO= M{LNZWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KEKFUmCgc5ZmemW6cILld5NqdmdiaIXtZY4hU0KKNT6wJINmdGy|IHHmeIVzKDRiZHH5d{BjgSCPVGSgcYV1cG:mLDDJR|UxRTBwMzFOwG0> Mk\lNVk{ODN|ME[=
human MCF-7 breast cell line M3LrfnBzd2yrZnXyZZRqd25iYYPzZZk> NUnLO|A3SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2YuPyCkcnXhd5Qh[2WubDDsbY5mNCCLQ{WwQVAvOzdizszN MWWxNFQ6QDJzNh?=
human SKOV-3 ovarian cell line NV7IOVlKWHKxbHnm[ZJifGmxbjDhd5NigQ>? MXHBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFONT2[tN{BwfmG{aXHuJINmdGxibHnu[UwhUUN3ME2wMlczKM7:TR?= Ml7tNVA1QTh{MU[=
human Bel-7402 liver cancer cell line Mn3WSpVv[3Srb36gZZN{[Xl? NEP1R3JKdmirYnn0c5J6KGOxbnPlcpRz[XSrb36gZYdicW6|dDDoeY1idiCEZXytO|QxOiCuaY\ldkBk[W6lZYKgZ4VtdCCuaX7lMEBKSzVyPUOuNVkh|ryP MYmxOVgxQDR3Nh?=
HEK293 cells NGjOXWdEgXSxdH;4bYPDqGG|c3H5 NIrYUYU4OiCq NUPrXXJpUW62cnnud4lkKGO7dH;0c5hq[2m2eTDh[4FqdnO2IFjFT|I6OyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigQ>? M3\QXlI2Ojd{MEW1

... 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
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.

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Topoisomerase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID