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

  • 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.

  • 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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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 M{jW[HBzd2yrZnXyZZRqd25iYYPzZZk> NHTYUpY3KGSjeYO= MkfXRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{[gZ4VtdHNiY3HydplqdmdicGLDJIFnfGW{IE[g[IF6eyxiSVO1NF0xNjR|IH7N MVyxPVI2PDh2Mx?=
human HCT116 cells MlixVJJwdGmoZYLheIlwdiCjc4PhfS=> NIjsd3A{KGSjeYO= NEHpc4tCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjDWFEyPiClZXzsd{Bi\nSncjCzJIRigXNuIFnDOVA:OC53NTDuUS=> MYKxPVI2PDh2Mx?=
human PC3 cells MnnMR5l1d3SxeHnjxsBie3OjeR?= MVK3NkBp MkjzR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVGM{KGOnbHzzJIV5eHKnc4Ppcoch[WyyaHG1ZoV1[TNiaX70[YdzcW5iYYPz[ZN{\WRiYYOgZ4VtdCC|dYL2bZZidCCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwQVIvPiCwTR?= NYDkdItoOjJ7NUmyOFY>
human A549 cells M3;sVWN6fG:2b4jpZ:Kh[XO|YYm= NGC0ZXc{KGSjeYO= NILEeFNEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDNiZHH5d{BjgSCVUlKgZZN{[XluIFnDOVA:Oi55MjDuUS=> MXuyOFUzQTh5MB?=
human QG56 cells NWHQb|dvWHKxbHnm[ZJifGmxbjDhd5NigQ>? Mnq4N{Bl[Xm| NEC5dopCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGHHOVYh[2WubIOgZYZ1\XJiMzDkZZl{NCCLQ{WwQVIvQCCwTR?= NXPoelVpOTl{NUS4OFM>
human NCI-H460 cells MULQdo9tcW[ncnH0bY9vKGG|c3H5 M{e5VlMh\GG7cx?= NGPoSVFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JPDZyIHPlcIx{KGGodHXyJFMh\GG7czygTWM2OD1|LkOgcm0> MnzhNVkzPTR6NEO=
human DU145 cells NWrRTmc2WHKxbHnm[ZJifGmxbjDhd5NigQ>? M3rVTlk3KGh? NETkVXZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFTVNVQ2KGOnbHzzJIFnfGW{IEm2JIhzeyxiSVO1NF01KG6P M2fm[FE5Ojd4MUSx
human breast cancer cell line (SK-BR-3) M13GeWN6fG:2b4jpZ:Kh[XO|YYm= M1j2WWlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJIJz\WG|dDDjZY5k\XJiY3XscEBtcW6nIDjTT{1DWi1|KTygTWM2OD12IH7N NX74bJJzOTF|M{S1Olk>
human KB3-1 cells Mn;JR5l1d3SxeHnjxsBie3OjeR?= M{L2NVQh\GG7cx?= NYnsbnB1S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU0J|LUGgZ4VtdHNiYX\0[ZIhPCCmYYnzJIJ6KE2WVDDt[ZRpd2RuIFnDOVA:PCCwTR?= M{Tt[VE6OzB|M{C2
human HCT116 cells M1r6fGN6fG:2b4jpZ:Kh[XO|YYm= NFPIOnQ4OiCq MkftR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGNVOTF4IHPlcIx{KGGodHXyJFczKGi{czDifUB{fWyob4Loc4RidWmwZTDCJIF{e2G7LDDJR|UxRTRwMkigcm0> NWHnc4k{OjV6M{WzOVk>
MDA-MB-435 S human breast cancer cells NUjaPJR6TnWwY4Tpc44h[XO|YYm= M1rxVGlvcGmkaYTpc44h[WejaX7zeEBOTEFvTVKtOFM2KFNiaIXtZY4h[nKnYYP0JINidmOncjDj[YxteyCrbjD0bIUh[WK|ZX7j[UBw\iCjbHL1cYlvNCCLQ{WwQVUhdk1? Mn71NVExPTJ6MEK=
human HT-29 cells MkjGR5l1d3SxeHnjxsBie3OjeR?= NF3pV2VEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJXC1{OTDj[YxteyxiSVO1NF02Njlibl2= MlLBNlE1PzB6NkS=
human lung cancer cell line (H128) M4T4[GN6fG:2b4jpZ:Kh[XO|YYm= M2fFfGlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJIx2dmdiY3HuZ4VzKGOnbHygcIlv\SBqSEGyPEktKEmFNUC9OkBvVQ>? MlLMNVE{OzR3Nkm=
human MIA PaCa cells MknwVJJwdGmoZYLheIlwdiCjc4PhfS=> NWj4V49HSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNTWEhWGGFYTDj[YxteyCjZoTldkA6PiCqcoOsJGlEPTB;NjDuUS=> NWP5d3I3OTh{N{[xOFE>
human HCT116 colon cancer cell line NGnRT|ZHfW6ldHnvckBie3OjeR?= M3XUcGlvcGmkaYTvdpkh[2:wY3XueJJifGmxbjDh[4FqdnO2IHj1cYFvKEiFVEGxOkBkd2yxbjDjZY5k\XJiY3XscEBtcW6nLDDJR|UxRTdibl2= MYSxOVgxQDR3Nh?=
human stomach cancer cell line (MKN45) M3HvS2N6fG:2b4jpZ:Kh[XO|YYm= NYfDV|g{UW5iVnn0do8h[3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4he3SxbXHjbEBk[W6lZYKgZ4VtdCCuaX7lJEhOU052NTmsJGlEPTB;ODDuUS=> MonjNVE{OzR3Nkm=
human A2780 cells MoixR5l1d3SxeHnjxsBie3OjeR?= MkLkO|IhcA>? MmraR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVI4QDBiY3XscJMhd3[ncnX4dJJme3OrbnegZYxxcGF3YnX0ZVMhcW62ZXfybY4h[XO|ZYPz[YQh[XNiY3XscEB{fXK4aY\hcEBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBKSzVyPUmgcm0> M1LoZVIzQTV7MkS2
human ovarian cancer cell line (SK-OV-3) NIiwVFFEgXSxdH;4bYPDqGG|c3H5 M2Ww[mlvKF[rdILvJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJI93[XKrYX6gZ4Fv[2W{IHPlcIwhdGmwZTCoV2suV1ZvMzmsJGlEPTB;MUGgcm0> MmnmNVE{OzR3Nkm=
human DU145 prostate cell line NV\GTmZyWHKxbHnm[ZJifGmxbjDhd5NigQ>? NHn5XopCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFTVNVQ2KHC{b4P0ZZRmKGOnbHygcIlv\SxiSVO1NF0yOyCwTR?= NXW0R|ViOTB2OUiyNVY>
human colon cancer cell line (WiDr) NFrQXnFEgXSxdH;4bYPDqGG|c3H5 NI\1ZYFKdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBkd2yxbjDjZY5k\XJiY3XscEBtcW6nIDjXbWRzMSxiSVO1NF0yPCCwTR?= MVWxNVM{PDV4OR?=
human lung cancer cell line (A549) NV3Oc4d4S3m2b4TvfIlkyqCjc4PhfS=> NXfBSXA1UW5iVnn0do8h[3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hdHWwZzDjZY5k\XJiY3XscEBtcW6nIDjBOVQ6MQ>? NF3FOpcyOTN|NEW2PS=>
human tumor HL60 cell-line MlrXSpVv[3Srb36gZZN{[Xl? NInlU|U{KGSjeYO= NGruTIVKdi24aYTyc{BqdmirYnn0c5J6KGOxbnPlcpRz[XSrb36g[o9zKGi3bXHuJJR2dW:{IFjMOlAh[2WubD3sbY5mKHejczDk[ZRmem2rbnXkJJV{cW6pIGPSRkBie3OjeTDh[pRmeiB|IHThfZMhd2ZiaX7jeYJifGmxbjygTWM2OD1zOTDuUS=> MVexOVkyOzl7Nh?=
PC-3 carcinoma cell line M1rlO2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NViwSJZzS2:wY3XueJJifGmxbjDy[ZF2cXKnZDD0c{BqdmirYnn0JIdzd3e2aDDv[kBpfW2jbjDwdo9{fGG2ZTDQR{0{KGOjcnPpco9u[SClZXzsJIxqdmVuIFnDOVA:OzVwNjDuUS=> NXKwcVlEOTV2NUSyN|A>
human KBV1 cells NH7Jd2xEgXSxdH;4bYPDqGG|c3H5 MkPzOEBl[Xm| MkTuR5l1d3SxeHnjbZR6KGGpYXnud5QhVUSUMTDveoVz\XiycnXzd4lv\yCqdX3hckBMSlZzIHPlcIx{KGGodHXyJFQh\GG7czDifUBOXFRibXX0bI9lNCCLQ{WwQVQ3KG6P NXGzc3IxOTl|MEOzNFY>
human A549 cells M3\CSmN6fG:2b4jpZ:Kh[XO|YYm= MXzDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzMEBKSzVyPUS3JI5O NGPUTIozOTR5MEi2OC=>
NSCLC-H460 MY\DfZRwfG:6aXRCpIF{e2G7 NHjFcm9EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBvd25vc33hcIwu[2WubDDseY5oKGOjcnPpco9u[SClZXzsJIxqdmViSES2NEApVlOFTFOtTFQ3OCluIFnDOVA:QDBibl2= NFi0dYoyOTV4M{myOS=>
MDA-MB-435 S human breast cancer cells MkDaSpVv[3Srb36gZZN{[Xl? MUXJcohq[mm2aX;uJIFo[Wmwc4SgUWRCNU2ELUSzOUBUKGi3bXHuJIJz\WG|dDDjZY5k\XJiY3XscJMhcW5idHjlJJBz\XOnbnPlJI9nKDNyIH3nM41NKEiVQTygTWM2OD13MDDuUS=> M4rjRlEyODV{OECy
human H460 cell MV3Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NHHPcY9KdmirYnn0bY9vKG:oIHj1cYFvKEh2NkCgZ4VtdCCpcn;3eIgtKEmFNUC9PFAhdk1? M4i0NFE3QTF|N{C2
human MDA-MB-231 cells NG\qSmxEgXSxdH;4bYPDqGG|c3H5 MVXDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy|LDDJR|UxRTF5NjDuUS=> M{PxSFI1PTJ7OEew
human KBH5.0 cells MmLWR5l1d3SxeHnjxsBie3OjeR?= NXz4TIFIPCCmYYnz M1PaWWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KEKFUmCgc5ZmemW6cILld5NqdmdiaIXtZY4hU0KKNT6wJINmdGy|IHHmeIVzKDRiZHH5d{BjgSCPVGSgcYV1cG:mLDDJR|UxRTBwMzFOwG0> M1fTZ|E6OzB|M{C2
human MCF-7 breast cell line M1OwWXBzd2yrZnXyZZRqd25iYYPzZZk> MlG4RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCPQ1[tO{BjemWjc4SgZ4VtdCCuaX7lMEBKSzVyPUCuN|ch|ryP MWGxNFQ6QDJzNh?=
human SKOV-3 ovarian cell line MY\Qdo9tcW[ncnH0bY9vKGG|c3H5 Mn7ZRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVS1;WMVMhd3[jcnnhckBk\WyuIHzpcoUtKEmFNUC9NE44OiEQvF2= M4TuS|ExPDl6MkG2
human Bel-7402 liver cancer cell line NHrqfmlHfW6ldHnvckBie3OjeR?= NWrocVZSUW6qaXLpeI9zgSClb37j[Y51emG2aX;uJIFo[Wmwc4SgbJVu[W5iQnXsMVc1ODJibHn2[ZIh[2GwY3XyJINmdGxibHnu[UwhUUN3ME2zMlE6KM7:TR?= M2fFSVE2QDB6NEW2
HEK293 cells MXvDfZRwfG:6aXRCpIF{e2G7 MlGyO|IhcA>? MWXJcpRzcW6|aXOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhUEWNMkmzJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5 MXuyOVI4OjB3NR?=

... 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
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