SN-38

For research use only.

Catalog No.S4908

23 publications

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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Selleck's SN-38 has been cited by 23 publications

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Choose Selective ADC Cytotoxin 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 Moi2VJJwdGmoZYLheIlwdiCjc4PhfS=> MVi2JIRigXN? NWHlU3E3SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDQR|Yh[2WubIOgZ4FzenmrbnegdHJEKGGodHXyJFYh\GG7czygTWM2OD1yLkSzJI5O NUXVdVJLOTl{NUS4OFM>
human HCT116 cells NF20WoRRem:uaX\ldoF1cW:wIHHzd4F6 NGi1WIg{KGSjeYO= M2DBRmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IEOg[IF6eyxiSVO1NF0xNjV3IH7N M17ZZ|E6OjV2OESz
human PC3 cells NUXEb414S3m2b4TvfIlkyqCjc4PhfS=> M3HtPFczKGh? NITyXFNEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSzNiY3XscJMh\XiycnXzd4lv\yCjbIDoZVVj\XSjMzDpcpRm\3KrbjDhd5Nme3OnZDDhd{Bk\WyuIIP1dpZqfmGuIHHmeIVzKDd{IHjyd{BjgSCVUlKgZZN{[XluIFnDOVA:Oi54IH7N M3\GVVIzQTV7MkS2
human A549 cells MojOR5l1d3SxeHnjxsBie3OjeR?= M321ZVMh\GG7cx?= MX7DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGGodHXyJFMh\GG7czDifUBUWkJiYYPzZZktKEmFNUC9Nk44OiCwTR?= NXHmUI1EOjR3Mkm4O|A>
human QG56 cells NVe2bZJiWHKxbHnm[ZJifGmxbjDhd5NigQ>? MoPQN{Bl[Xm| MVfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFGJNU[gZ4VtdHNiYX\0[ZIhOyCmYYnzMEBKSzVyPUKuPEBvVQ>? MkHMNVkzPTR6NEO=
human NCI-H460 cells M2TaW3Bzd2yrZnXyZZRqd25iYYPzZZk> NU\KWlNUOyCmYYnz MlXBRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCQQ1mtTFQ3OCClZXzsd{Bi\nSncjCzJIRigXNuIFnDOVA:Oy5|IH7N M3XvOFE6OjV2OESz
human DU145 cells M4PEZXBzd2yrZnXyZZRqd25iYYPzZZk> MVO5OkBp MkDzRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCGVUG0OUBk\WyuczDh[pRmeiB7NjDodpMtKEmFNUC9OEBvVQ>? MmjlNVgzPzZzNEG=
human breast cancer cell line (SK-BR-3) NWTsbG92S3m2b4TvfIlkyqCjc4PhfS=> MUnJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDidoVie3RiY3HuZ4VzKGOnbHygcIlv\SBqU1utRnIuOyluIFnDOVA:PCCwTR?= MYCxNVM{PDV4OR?=
human KB3-1 cells M4jk[WN6fG:2b4jpZ:Kh[XO|YYm= M{jFXFQh\GG7cx?= NV;3dlVkS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU0J|LUGgZ4VtdHNiYX\0[ZIhPCCmYYnzJIJ6KE2WVDDt[ZRpd2RuIFnDOVA:PCCwTR?= NFj0O2EyQTNyM{OwOi=>
human HCT116 cells NXvYZmFtS3m2b4TvfIlkyqCjc4PhfS=> Mo\5O|IhcA>? NWTrSlBoS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUEOWMUG2JINmdGy|IHHmeIVzKDd{IHjyd{BjgSC|dXzmc5Jpd2SjbXnu[UBDKGG|c3H5MEBKSzVyPUSuNlghdk1? M3ziZVI2QDN3M{W5
MDA-MB-435 S human breast cancer cells M{e4d2Z2dmO2aX;uJIF{e2G7 MVjJcohq[mm2aX;uJIFo[Wmwc4SgUWRCNU2ELUSzOUBUKGi3bXHuJIJz\WG|dDDjZY5k\XJiY3XscJMhcW5idHjlJIFje2WwY3Wgc4Yh[WykdX3pckwhUUN3ME21JI5O MkPGNVExPTJ6MEK=
human HT-29 cells NX7WN5JqS3m2b4TvfIlkyqCjc4PhfS=> M1rVcWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhVNTJ7IHPlcIx{NCCLQ{WwQVUvQSCwTR?= M{DZWFIyPDdyOE[0
human lung cancer cell line (H128) MVjDfZRwfG:6aXRCpIF{e2G7 MVzJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDseY5oKGOjbnPldkBk\WyuIHzpcoUhMEhzMkipMEBKSzVyPU[gcm0> NHrRcJEyOTN|NEW2PS=>
human MIA PaCa cells MmXTVJJwdGmoZYLheIlwdiCjc4PhfS=> M1z1RmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVnBJHBiS2FiY3XscJMh[W[2ZYKgPVYhcHK|LDDJR|UxRTZibl2= NF7IeJcyQDJ5NkG0NS=>
human HCT116 colon cancer cell line Ml\sSpVv[3Srb36gZZN{[Xl? M32zcmlvcGmkaYTvdpkh[2:wY3XueJJifGmxbjDh[4FqdnO2IHj1cYFvKEiFVEGxOkBkd2yxbjDjZY5k\XJiY3XscEBtcW6nLDDJR|UxRTdibl2= NYTV[W9HOTV6MEi0OVY>
human stomach cancer cell line (MKN45) NV2wcGFQS3m2b4TvfIlkyqCjc4PhfS=> MV;JckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDzeI9u[WOqIHPhcoNmeiClZXzsJIxqdmViKF3LUlQ2MSxiSVO1NF05KG6P NELkNooyOTN|NEW2PS=>
human A2780 cells NYfE[HZvS3m2b4TvfIlkyqCjc4PhfS=> NHf1WJE4OiCq MkHBR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVI4QDBiY3XscJMhd3[ncnX4dJJme3OrbnegZYxxcGF3YnX0ZVMhcW62ZXfybY4h[XO|ZYPz[YQh[XNiY3XscEB{fXK4aY\hcEBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBKSzVyPUmgcm0> NV32fYt4OjJ7NUmyOFY>
human ovarian cancer cell line (SK-OV-3) M4\NRWN6fG:2b4jpZ:Kh[XO|YYm= MVLJckBXcXS{bzDjfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDveoFzcWGwIHPhcoNmeiClZXzsJIxqdmViKGPLMW9XNTNrLDDJR|UxRTFzIH7N M3HOOlEyOzN2NU[5
human DU145 prostate cell line M4DHZ3Bzd2yrZnXyZZRqd25iYYPzZZk> MkCyRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCGVUG0OUBxem:|dHH0[UBk\WyuIHzpcoUtKEmFNUC9NVMhdk1? MVixNFQ6QDJzNh?=
human colon cancer cell line (WiDr) NWDWUmJnS3m2b4TvfIlkyqCjc4PhfS=> NX\3XooyUW5iVnn0do8h[3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4h[2:ub36gZ4Fv[2W{IHPlcIwhdGmwZTCoW4lFeiluIFnDOVA:OTRibl2= NWLWb4ZnOTF|M{S1Olk>
human lung cancer cell line (A549) MnXpR5l1d3SxeHnjxsBie3OjeR?= NGPBNY5KdiCYaYTyc{BkgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBtfW6pIHPhcoNmeiClZXzsJIxqdmViKFG1OFkq MUixNVM{PDV4OR?=
human tumor HL60 cell-line NFHBUVNHfW6ldHnvckBie3OjeR?= MlvRN{Bl[Xm| M{TlS2lvNX[rdILvJIlvcGmkaYTvdpkh[2:wY3XueJJifGmxbjDmc5IhcHWvYX6geJVud3JiSFy2NEBk\WyuLXzpcoUhf2G|IHTleIVzdWmwZXSgeZNqdmdiU2LCJIF{e2G7IHHmeIVzKDNiZHH5d{Bw\iCrbnP1ZoF1cW:wLDDJR|UxRTF7IH7N MVyxOVkyOzl7Nh?=
PC-3 carcinoma cell line M1HhTmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MoPmR49v[2WwdILheIlwdiC{ZYH1bZJm\CC2bzDpcohq[mm2IHfyc5d1cCCxZjDoeY1idiCycn;zeIF1\SCSQz2zJINiemOrbn;tZUBk\WyuIHzpcoUtKEmFNUC9N|UvPiCwTR?= Ml3zNVU1PTR{M{C=
human KBV1 cells NFvS[INEgXSxdH;4bYPDqGG|c3H5 MX[0JIRigXN? MWPDfZRwfG:6aXPpeJkh[WejaX7zeEBOTFJzIH;2[ZJmgHC{ZYPzbY5oKGi3bXHuJGtDXjFiY3XscJMh[W[2ZYKgOEBl[Xm|IHL5JG1VXCCvZYToc4QtKEmFNUC9OFYhdk1? M1jvVVE6OzB|M{C2
human A549 cells Mn7LR5l1d3SxeHnjxsBie3OjeR?= NV7sc2RWS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTV2OTDj[YxteyxiSVO1NF01PyCwTR?= MlzQNlE1PzB6NkS=
NSCLC-H460 MnrYR5l1d3SxeHnjxsBie3OjeR?= NHnFfWVEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBvd25vc33hcIwu[2WubDDseY5oKGOjcnPpco9u[SClZXzsJIxqdmViSES2NEApVlOFTFOtTFQ3OCluIFnDOVA:QDBibl2= NUXOWo1IOTF3NkO5NlU>
MDA-MB-435 S human breast cancer cells NEnsSpJHfW6ldHnvckBie3OjeR?= MYrJcohq[mm2aX;uJIFo[Wmwc4SgUWRCNU2ELUSzOUBUKGi3bXHuJIJz\WG|dDDjZY5k\XJiY3XscJMhcW5idHjlJJBz\XOnbnPlJI9nKDNyIH3nM41NKEiVQTygTWM2OD13MDDuUS=> NH61VmgyOTB3MkiwNi=>
human H460 cell M3n6NGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkDNTY5pcWKrdHnvckBw\iCqdX3hckBJPDZyIHPlcIwh\3Kxd4ToMEBKSzVyPUiwJI5O M1e1WVE3QTF|N{C2
human MDA-MB-231 cells MWrDfZRwfG:6aXRCpIF{e2G7 NWPDS4Y6S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUSDLV3CMVI{OSClZXzsd{whUUN3ME2xO|Yhdk1? NETLV48zPDV{OUi3NC=>
human KBH5.0 cells M1n5cWN6fG:2b4jpZ:Kh[XO|YYm= NED4T5I1KGSjeYO= NY\CWXpSS3m2b4TvfIlkcXS7IHHnZYlve3RiQlPSVEBwfmW{ZYjwdoV{e2mwZzDoeY1idiCNQli1MlAh[2WubIOgZYZ1\XJiNDDkZZl{KGK7IF3UWEBu\XSqb3SsJGlEPTB;MD6zJO69VQ>? NXzwVmRCOTl|MEOzNFY>
human MCF-7 breast cell line Mnn5VJJwdGmoZYLheIlwdiCjc4PhfS=> MVjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2FRj23JIJz\WG|dDDj[YxtKGyrbnWsJGlEPTB;MD6zO{DPxE1? NHvncpAyODR7OEKxOi=>
human SKOV-3 ovarian cell line NU\SUohlWHKxbHnm[ZJifGmxbjDhd5NigQ>? Mle1RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVS1;WMVMhd3[jcnnhckBk\WyuIHzpcoUtKEmFNUC9NE44OiEQvF2= Ml;3NVA1QTh{MU[=
human Bel-7402 liver cancer cell line MmXLSpVv[3Srb36gZZN{[Xl? MlHHTY5pcWKrdH;yfUBkd26lZX70doF1cW:wIHHnZYlve3RiaIXtZY4hSmWuLUe0NFIhdGm4ZYKgZ4Fv[2W{IHPlcIwhdGmwZTygTWM2OD1|LkG5JO69VQ>? M33HV|E2QDB6NEW2
HEK293 cells MWLDfZRwfG:6aXRCpIF{e2G7 MUK3NkBp MYjJcpRzcW6|aXOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhUEWNMkmzJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5 NXS4bYFyOjV{N{KwOVU>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-Chk1 / Chk1 / Topo I ; 

PubMed: 18509065     


Log-phase Ovcar-5 cells were treated for 24 h with diluent (0.1% DMSO, lanes 1 and 6), gemcitabine at 12.5, 25, 50 or 100 nM (lanes 2-5, respectively), or SN-38 at 2.5, 5, 10, 20 and 40 nM in the absence (lanes 7-11) or presence (lanes 12-17) of 50 nM gemcitabine. At the end of the incubation, whole cell lysates were prepared, subjected to SDS-PAGE, transferred to nitrocellulose, and probed with reagents that recognize phospho-Ser345-Chk1, total Chk1, topo I or, as control, β-actin. Because of the limited number of lanes on our electrophoresis apparatus, lanes 1-5 and 6-17 represent two different membranes from the same experiment that were probed simultaneously.

18509065
Growth inhibition assay
Cell viability; 

PubMed: 25759163     


(A) Drug sensitivity towards SN‐38 and oxaliplatin for the parental and drug resistant cell lines. Cells were exposed to a range of drug concentrations for 48 h and cell viability was assessed by an endpoint MTT assay. Results of representative experiments are shown. Green (triangle) is the parental cell line, blue (diamond) the SN‐38 resistant cell line, and red (square) the oxaliplatin resistant cell line.

25759163
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
Smiles CCC1=C2CN3C(=O)C4=C(C=C3C2=NC5=C1C=C(O)C=C5)C(O)(CC)C(=O)OC4

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03964727 Suspended Biological: IMMU-132 Metastatic Non-Small Cell Lung Carcinoma|Head and Neck Squamous Cell Carcinoma|Endometrial Cancer Immunomedics Inc. August 6 2019 Phase 2
NCT03995706 Recruiting Drug: Sacituzumab Govitecan Glioblastoma The University of Texas Health Science Center at San Antonio|Immunomedics Inc. July 17 2019 Early Phase 1
NCT03221400 Recruiting Drug: PEN-866 Sodium Carcinoma|Endometrial Adenocarcinoma|Neoplasms|Squamous Cell Carcinoma of the Anus|Adenocarcinoma of the Pancreas|Advanced Cancer|Solid Tumor|Solid Carcinoma|Squamous Cell Carcinoma of the Cervix|Squamous Cell Carcinoma|Squamous Cell Carcinoma of the Vulva|Squamous Cell Carcinoma of the Penis|Gastric Cancer|Gastric Adenocarcinoma|Gastroesophageal Junction Adenocarcinoma|Small-cell Lung Cancer|Small Cell Lung Carcinoma|Pancreatic Ductal Adenocarcinoma|Pancreatic Adenocarcinoma Tarveda Therapeutics August 29 2017 Phase 1|Phase 2
NCT03096340 Unknown status Drug: IT-141 Cancer|Neoplasms|Tumors|Refractory Solid Tumors|Recurrent Solid Tumors Intezyne Technologies Inc. March 23 2017 Phase 1
NCT02785068 Withdrawn Drug: MM-151|Drug: nal-IRI|Drug: Leucovorin|Drug: 5-FU Colorectal Cancer Merrimack Pharmaceuticals July 2016 Phase 1|Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID