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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Cited by 10 Publications

5 Customer Reviews

  • 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.

    CRC lung metastasis was established after iv injection of HT-29 LuM3 cells (1.5×106 cells in 100 μl of PBS). The polymeric nanoparticles loaded with PX866 and SN-38 were administered iv 72h after HT-29 LuM3 cells injection every q24h for 4 days and continued every q72h for 26 days (10 μg/g dose in 300 μl of PBS). PX866+SN−38 combination treatment was administered iv 72h after HT-29 LuM3 cells injection every q24h for 4 days (10 μg/g PX866 + 10 μg/g SN-38 mixed in 300 μl of PBS). Control: Empty PNP. Green: GFP expressing HT-29 LuM3 cells.

    J Control Release, 2018, 275:85-91. SN-38 purchased from Selleck.

  • Antiproliferative effects of SN-38 in vitro on 8305C (C) and FB3 (D) cell lines. The antiproliferative effects of the drugs were studied after 72 h of exposure. The data are presented as percentage of vehicle-treated cells. The concentrations of drug that reduced cell proliferation by 50% (IC50) vs controls were calculated by a nonlinear regression fit of the mean values of the data obtained in triplicate experiments (i.e. at least 9 wells for each concentration). Columns and bars, mean values ± S.E., respectively. *, P < 0.001 vs. control.

    Cancer Lett, 2017, 411:35-43. SN-38 purchased from Selleck.

    (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.

  • Following incubation of Hep3B cells with SN-38, mRNA expression levels of FUBP1 target genes (p21, BIK, CCND2 and TCTP) were significantly deregulated, whereas FUBP1 protein levels were not influenced.

    Biochem Pharmacol, 2017, 146:53-62. SN-38 purchased from Selleck.

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Choose Selective Topoisomerase Inhibitors

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 M2C4bHBzd2yrZnXyZZRqd25iYYPzZZk> M2X4PFYh\GG7cx?= MXnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFCFNjDj[YxteyClYYLyfYlv\yCyUlOgZYZ1\XJiNjDkZZl{NCCLQ{WwQVAvPDNibl2= NUDj[lRUOTl{NUS4OFM>
human HCT116 cells NV3KdYY4WHKxbHnm[ZJifGmxbjDhd5NigQ>? NIfzR2g{KGSjeYO= NESxVmJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjDWFEyPiClZXzsd{Bi\nSncjCzJIRigXNuIFnDOVA:OC53NTDuUS=> M{SweVE6OjV2OESz
human PC3 cells NWnLSlBuS3m2b4TvfIlkyqCjc4PhfS=> MXm3NkBp M2nZUWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHBEOyClZXzsd{BmgHC{ZYPzbY5oKGGucHjhOYJmfGF|IHnueIVoemmwIHHzd4V{e2WmIHHzJINmdGxic4Xyeol3[WxiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NF0zNjZibl2= NGjSNnIzOjl3OUK0Oi=>
human A549 cells Ml;VR5l1d3SxeHnjxsBie3OjeR?= NGm0[nY{KGSjeYO= MV\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGGodHXyJFMh\GG7czDifUBUWkJiYYPzZZktKEmFNUC9Nk44OiCwTR?= NHvYc3kzPDV{OUi3NC=>
human QG56 cells MUjQdo9tcW[ncnH0bY9vKGG|c3H5 MYmzJIRigXN? NIrIbnJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGHHOVYh[2WubIOgZYZ1\XJiMzDkZZl{NCCLQ{WwQVIvQCCwTR?= Mny2NVkzPTR6NEO=
human NCI-H460 cells MULQdo9tcW[ncnH0bY9vKGG|c3H5 NHyyToI{KGSjeYO= MoriRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCQQ1mtTFQ3OCClZXzsd{Bi\nSncjCzJIRigXNuIFnDOVA:Oy5|IH7N NXf1NXlDOTl{NUS4OFM>
human DU145 cells M2PGd3Bzd2yrZnXyZZRqd25iYYPzZZk> MYW5OkBp NVTrdXNRSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDEWVE1PSClZXzsd{Bi\nSncjC5OkBpenNuIFnDOVA:PCCwTR?= M1i0T|E5Ojd4MUSx
human breast cancer cell line (SK-BR-3) MUPDfZRwfG:6aXRCpIF{e2G7 M3HNeWlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJIJz\WG|dDDjZY5k\XJiY3XscEBtcW6nIDjTT{1DWi1|KTygTWM2OD12IH7N MXWxNVM{PDV4OR?=
human KB3-1 cells MmXDR5l1d3SxeHnjxsBie3OjeR?= NEnqfVM1KGSjeYO= M4f0bWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtDOy1zIHPlcIx{KGGodHXyJFQh\GG7czDifUBOXFRibXX0bI9lNCCLQ{WwQVQhdk1? MVWxPVMxOzNyNh?=
human HCT116 cells NWPkRnFwS3m2b4TvfIlkyqCjc4PhfS=> MlTsO|IhcA>? MVzDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JJN2dG[xcnjv[IFucW6nIFKgZZN{[XluIFnDOVA:PC5{ODDuUS=> M1PuUVI2QDN3M{W5
MDA-MB-435 S human breast cancer cells NGLKXplHfW6ldHnvckBie3OjeR?= Mmj4TY5pcWKrdHnvckBi\2GrboP0JG1FSS2PQj20N|UhWyCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIx{KGmwIITo[UBi[nOnbnPlJI9nKGGuYoXtbY4tKEmFNUC9OUBvVQ>? NEe1[4QyOTB3MkiwNi=>
human HT-29 cells NWfmc481S3m2b4TvfIlkyqCjc4PhfS=> NFmxfGtEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJXC1{OTDj[YxteyxiSVO1NF02Njlibl2= NWDXfVR3OjF2N{C4OlQ>
human lung cancer cell line (H128) MmPxR5l1d3SxeHnjxsBie3OjeR?= Mk\oTY4hXmm2cn:gZ5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gcJVv\yClYX7j[ZIh[2WubDDsbY5mKCiKMUK4LUwhUUN3ME22JI5O NI[3bXcyOTN|NEW2PS=>
human MIA PaCa cells MVzQdo9tcW[ncnH0bY9vKGG|c3H5 M1fldGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVnBJHBiS2FiY3XscJMh[W[2ZYKgPVYhcHK|LDDJR|UxRTZibl2= NVrs[mcyOTh{N{[xOFE>
human HCT116 colon cancer cell line M3nhNmZ2dmO2aX;uJIF{e2G7 MYXJcohq[mm2b4L5JINwdmOnboTyZZRqd25iYXfhbY5{fCCqdX3hckBJS1RzMU[gZ49td25iY3HuZ4VzKGOnbHygcIlv\SxiSVO1NF04KG6P MlLCNVU5ODh2NU[=
human stomach cancer cell line (MKN45) NWTWV3h5S3m2b4TvfIlkyqCjc4PhfS=> NFzNV2pKdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckB{fG:vYXPoJINidmOncjDj[YxtKGyrbnWgLG1MVjR3KTygTWM2OD16IH7N NWT0NodPOTF|M{S1Olk>
human A2780 cells MkD3R5l1d3SxeHnjxsBie3OjeR?= M{ny[|czKGh? MXPDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBNlc5OCClZXzsd{BwfmW{ZYjwdoV{e2mwZzDhcJBp[TWkZYThN{BqdnSnZ4LpckBie3Onc4Pl[EBieyClZXzsJJN2en[rdnHsJIFnfGW{IEeyJIhzeyCkeTDTVmIh[XO|YYmsJGlEPTB;OTDuUS=> NF;LeWIzOjl3OUK0Oi=>
human ovarian cancer cell line (SK-OV-3) M3fXXmN6fG:2b4jpZ:Kh[XO|YYm= M17QPWlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJI93[XKrYX6gZ4Fv[2W{IHPlcIwhdGmwZTCoV2suV1ZvMzmsJGlEPTB;MUGgcm0> NW\U[GJqOTF|M{S1Olk>
human DU145 prostate cell line NV70T4pXWHKxbHnm[ZJifGmxbjDhd5NigQ>? M2L3ZWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iRGWxOFUheHKxc4TheIUh[2WubDDsbY5mNCCLQ{WwQVE{KG6P M3jKPFExPDl6MkG2
human colon cancer cell line (WiDr) NF;jdFNEgXSxdH;4bYPDqGG|c3H5 M3PYSmlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJINwdG:wIHPhcoNmeiClZXzsJIxqdmViKGfpSJIqNCCLQ{WwQVE1KG6P NID1R3EyOTN|NEW2PS=>
human lung cancer cell line (A549) NVLwUFAxS3m2b4TvfIlkyqCjc4PhfS=> NI\RVlZKdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBtfW6pIHPhcoNmeiClZXzsJIxqdmViKFG1OFkq MVixNVM{PDV4OR?=
human tumor HL60 cell-line NUTVUodxTnWwY4Tpc44h[XO|YYm= M1HYSVMh\GG7cx?= MlzMTY4ufmm2cn:gbY5pcWKrdH;yfUBkd26lZX70doF1cW:wIH\vdkBpfW2jbjD0eY1weiCKTE[wJINmdGxvbHnu[UB4[XNiZHX0[ZJucW6nZDD1d4lv\yCVUlKgZZN{[XliYX\0[ZIhOyCmYYnzJI9nKGmwY4XiZZRqd25uIFnDOVA:OTlibl2= Ml72NVU6OTN7OU[=
PC-3 carcinoma cell line NFrVTZlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3PnUGNwdmOnboTyZZRqd25icnXxeYlz\WRidH:gbY5pcWKrdDDndo94fGhib3[gbJVu[W5icILvd5RifGViUFOtN{Bk[XKlaX7vcYEh[2WubDDsbY5mNCCLQ{WwQVM2NjZibl2= NED1RXMyPTR3NEKzNC=>
human KBV1 cells M4jFS2N6fG:2b4jpZ:Kh[XO|YYm= NYTKTItOPCCmYYnz NH\4OG5EgXSxdH;4bYNqfHliYXfhbY5{fCCPRGKxJI93\XKneIDy[ZN{cW6pIHj1cYFvKEuEVkGgZ4VtdHNiYX\0[ZIhPCCmYYnzJIJ6KE2WVDDt[ZRpd2RuIFnDOVA:PDZibl2= MY[xPVMxOzNyNh?=
human A549 cells M3XlN2N6fG:2b4jpZ:Kh[XO|YYm= MkO1R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVU1QSClZXzsd{whUUN3ME20O{BvVQ>? MnrjNlE1PzB6NkS=
NSCLC-H460 M1TiU2N6fG:2b4jpZ:Kh[XO|YYm= Mnn1R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gco9vNXOvYXzsMYNmdGxibIXu[{Bk[XKlaX7vcYEh[2WubDDsbY5mKEh2NkCgLG5US0yFLVi0OlAqNCCLQ{WwQVgxKG6P MVexNVU3Ozl{NR?=
MDA-MB-435 S human breast cancer cells Mo\RSpVv[3Srb36gZZN{[Xl? MkDpTY5pcWKrdHnvckBi\2GrboP0JG1FSS2PQj20N|UhWyCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIx{KGmwIITo[UBxemW|ZX7j[UBw\iB|MDDt[{9uVCCKU1GsJGlEPTB;NUCgcm0> M1;JV|EyODV{OECy
human H460 cell M4\5Tmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NUfLXmx7UW6qaXLpeIlwdiCxZjDoeY1idiCKNE[wJINmdGxiZ4Lve5RpNCCLQ{WwQVgxKG6P M2e2XFE3QTF|N{C2
human MDA-MB-231 cells MnTlR5l1d3SxeHnjxsBie3OjeR?= MmLJR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWRCNU2ELUKzNUBk\WyuczygTWM2OD1zN{[gcm0> MlTvNlQ2Ojl6N{C=
human KBH5.0 cells M3XjV2N6fG:2b4jpZ:Kh[XO|YYm= NH3FNoU1KGSjeYO= NGnSXXREgXSxdH;4bYNqfHliYXfhbY5{fCCEQ2LQJI93\XKneIDy[ZN{cW6pIHj1cYFvKEuESEWuNEBk\WyuczDh[pRmeiB2IHThfZMh[nliTWTUJI1mfGixZDygTWM2OD1yLkOg{txO NVLYb5dtOTl|MEOzNFY>
human MCF-7 breast cell line Mnq1VJJwdGmoZYLheIlwdiCjc4PhfS=> M4\2V2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVPGMVch[nKnYYP0JINmdGxibHnu[UwhUUN3ME2wMlM4KM7:TR?= MXSxNFQ6QDJzNh?=
human SKOV-3 ovarian cell line NGe5NVhRem:uaX\ldoF1cW:wIHHzd4F6 NVm0PGpPSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTT29XNTNib4\hdolidiClZXzsJIxqdmVuIFnDOVA:OC55MjFOwG0> M4\IRVExPDl6MkG2
human Bel-7402 liver cancer cell line NV;zVJdtTnWwY4Tpc44h[XO|YYm= M2P4N2lvcGmkaYTvdpkh[2:wY3XueJJifGmxbjDh[4FqdnO2IHj1cYFvKEKnbD23OFAzKGyrdnXyJINidmOncjDj[YxtKGyrbnWsJGlEPTB;Mz6xPUDPxE1? M2r3eVE2QDB6NEW2
HEK293 cells MkD4R5l1d3SxeHnjxsBie3OjeR?= MUK3NkBp NXTs[JRLUW62cnnud4lkKGO7dH;0c5hq[2m2eTDh[4FqdnO2IFjFT|I6OyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigQ>? NHK1UGozPTJ5MkC1OS=>

... 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]
+ Expand

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]
+ Expand
  • 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
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
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
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