Home DNA Damage/DNA Repair ADC Cytotoxin inhibitor SN-38

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SN-38 Topoisomerase I inhibitor

Cat.No.S4908

SN-38 (NK012) is an active metabolite of CPT-11, inhibits DNA topoisomerase I, DNA synthesis and causes frequent DNA single-strand breaks. SN-38 induces autophagy.
SN-38 ADC Cytotoxin inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 392.4

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Quality Control

Batch: Purity: 99.96%
99.96

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human DU145 prostate cell line Proliferation assay Antiproliferative activity against human DU145 prostate cell line, IC50=13 nM 10498216
human MCF-7 breast cell line Proliferation assay Antiproliferative activity against human MCF-7 breast cell line, IC50=0.37 μM 10498216
human SKOV-3 ovarian cell line Proliferation assay Antiproliferative activity against human SKOV-3 ovarian cell line, IC50=0.72 μM 10498216
human breast cancer cell line (SK-BR-3) Cytotoxic assay In Vitro cytotoxicity against human breast cancer cell line (SK-BR-3), IC50=4 nM 11334569
human lung cancer cell line (H128) Cytotoxic assay In Vitro cytotoxicity against human lung cancer cell line (H128), IC50=6 nM 11334569
human stomach cancer cell line (MKN45) Cytotoxic assay In Vitro cytotoxicity against human stomach cancer cell line (MKN45), IC50=8 nM 11334569
human ovarian cancer cell line (SK-OV-3) Cytotoxic assay In Vitro cytotoxicity against human ovarian cancer cell line (SK-OV-3), IC50=11 nM 11334569
human colon cancer cell line (WiDr) Cytotoxic assay In Vitro cytotoxicity against human colon cancer cell line (WiDr), IC50=14 nM 11334569
human lung cancer cell line (A549) Cytotoxic assay In Vitro cytotoxicity against human lung cancer cell line (A549) 11334569
NSCLC-H460 Cytotoxic assay Cytotoxicity against human non-small-cell lung carcinoma cell line H460 (NSCLC-H460), IC50=80 nM 11563925
PC-3 carcinoma cell line Growth inhibition assay Concentration required to inhibit growth of human prostate PC-3 carcinoma cell line, IC50=35.6 nM 15454230
human HCT116 colon cancer cell line Function assay Inhibitory concentration against human HCT116 colon cancer cell line, IC50=7 nM 15808456
human Bel-7402 liver cancer cell line Function assay Inhibitory concentration against human Bel-7402 liver cancer cell line, IC50=3.19 μM 15808456
human tumor HL60 cell-line Function assay 3 days In-vitro inhibitory concentration for human tumor HL60 cell-line was determined using SRB assay after 3 days of incubation, IC50=19 nM 15913996
human H460 cell Growth inhibition assay Inhibition of human H460 cell growth, IC50=80 nM 16913706
MDA-MB-435 Function assay Inhibition against MDA-MB-435 S human breast cancer cells in the absence of albumin, IC50 = 0.005 μM. 11052802
MDA-MB-435 Function assay Inhibition against MDA-MB-435 S human breast cancer cells in the presence of 30 mg/mL HSA, IC50 = 0.05 μM. 11052802
PC-6/SN2-5H Function assay TP_TRANSPORTER: uptake in membrane vesicle from PC-6/SN2-5H cells, Km = 4 μM. 11688982
HT-29 Function assay In vitro inhibitory concentration required against HT-29 human colon cancer cells, IC50 = 0.0273 μM. 12617927
SaoS2 Function assay TP_TRANSPORTER: drug resistance(Imatinib mesylate) in BCRP-expressing SaoS2 cells, IC50 = 0.176 μM. 15059881
DU145 Antiproliferative assay 96 hrs Antiproliferative activity against human DU145 cells after 96 hrs, IC50 = 0.004 μM. 18276141
MIA PaCa Antiproliferative assay 96 hrs Antiproliferative activity against human MIA PaCa cells after 96 hrs, IC50 = 0.006 μM. 18276141
HT29 Antiproliferative assay 96 hrs Antiproliferative activity against human HT29 cells after 96 hrs, IC50 = 0.012 μM. 18276141
H460 Antiproliferative assay 1 hr Antiproliferative activity against human H460 cells after 1 hr of drug exposure measured after 72 hrs, IC50 = 0.22 μM. 18424133
HT29 Antiproliferative assay 1 hr Antiproliferative activity against human HT29 cells after 1 hr of drug exposure measured after 72 hrs, IC50 = 0.67 μM. 18424133
HT29 Antiproliferative assay 1 hr Antiproliferative activity against BCRP overexpressing mitoxantrone-resistant human HT29 cells after 1 hr of drug exposure measured after 72 hrs, IC50 = 11.5 μM. 18424133
H460 Cytotoxicity assay Cytotoxicity against human H460 cells, IC50 = 0.22 μM. 18434153
A549 Cytotoxicity assay Cytotoxicity against human A549 cells by SRB method, IC50 = 0.08 μM. 18986807
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells by SRB method, IC50 = 0.12 μM. 18986807
PC6 Antiproliferative assay 6 days Antiproliferative activity against human PC6 cells carrying pRC after 6 days, IC50 = 0.00043 μM. 19254843
HCT116 Antiproliferative assay 3 days Antiproliferative activity against human HCT116 cells after 3 days, IC50 = 0.00055 μM. 19254843
QG56 Antiproliferative assay 3 days Antiproliferative activity against human QG56 cells after 3 days, IC50 = 0.0028 μM. 19254843
NCI-H460 Antiproliferative assay 3 days Antiproliferative activity against human NCI-H460 cells after 3 days, IC50 = 0.0033 μM. 19254843
BCRP Antiproliferative assay 6 days Antiproliferative activity against human PC6 expressing BCRP cells after 6 days, IC50 = 0.0051 μM. 19254843
KB3-1 Cytotoxicity assay 4 days Cytotoxicity against human KB3-1 cells after 4 days by MTT method, IC50 = 0.004 μM. 19303306
KBV1 Cytotoxicity assay 4 days Cytotoxicity against MDR1 overexpressing human KBV1 cells after 4 days by MTT method, IC50 = 0.046 μM. 19303306
KBH5.0 Cytotoxicity assay 4 days Cytotoxicity against BCRP overexpressing human KBH5.0 cells after 4 days by MTT method, IC50 = 0.3 μM. 19303306
NCI-H460 Antiproliferative assay 1 hr Antiproliferative activity against human NCI-H460 cells after short term exposure for 1 hr measured after 72 hrs in drug-free medium, IC50 = 0.13 μM. 19530720
A549/ATCC Antitumor assay Antitumor activity against human A549/ATCC cells by SRB method, IC50 = 0.088 μM. 19541483
HT-29 Antitumor assay Antitumor activity against human HT-29 cells by SRB method, IC50 = 0.17 μM. 19541483
gastric cancer cells Growth inhibition assay 72 hrs Growth inhibition of human gastric cancer cells after 72 hrs by sulforhodamine B assay, GI50 = 0.066 μM. 20884089
lung cancer cells Growth inhibition assay 72 hrs Growth inhibition of human lung cancer cells after 72 hrs by sulforhodamine B assay, GI50 = 0.066 μM. 20884089
colon cancer cells Growth inhibition assay 72 hrs Growth inhibition of human colon cancer cells after 72 hrs by sulforhodamine B assay, GI50 = 0.066 μM. 20884089
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells, IC50 = 0.0059 μM. 21470864
A549 Cytotoxicity assay Cytotoxicity against human A549 cells, IC50 = 0.047 μM. 21470864
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells expressing alpha5beta3 integrin assessed as cell survival after 72 hrs by SRB assay, IC50 = 0.0026 μM. 22959246
A2780 Cytotoxicity assay 72 hrs Cytotoxicity against human A2780 cells overexpressing alpha5beta3 integrin assessed as cell survival after 72 hrs by SRB assay, IC50 = 0.009 μM. 22959246
DU145 Cytotoxicity assay Cytotoxicity against human DU145 cells, IC50 = 0.03 μM. 23578545
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells, IC50 = 0.03 μM. 23578545
L1210 Cytotoxicity assay Cytotoxicity against mouse L1210 cells, IC50 = 0.04 μM. 23578545
DU145 Cytotoxicity assay 72 hrs Cytotoxicity against human DU145 cells assessed as inhibition of cell viability after 72 hrs by MTS assay, IC50 = 0.11 μM. 23622981
DU145 Function assay 0.1 to 0.5 uM 24 hrs Inhibition of HDAC in human DU145 cells assessed as upregulation of p21waf1 expression at 0.1 to 0.5 uM after 24 hrs by Western blot analysis 23622981
A549 Cytotoxicity assay 3 days Cytotoxicity against human A549 cells assessed as growth inhibition after 3 days by SRB assay, IC50 = 0.00272 μM. 24529870
HCT116 Cytotoxicity assay 3 days Cytotoxicity against human HCT116 cells assessed as growth inhibition after 3 days by SRB assay, IC50 = 0.031 μM. 24529870
HT-29 Cytotoxicity assay 3 days Cytotoxicity against human HT-29 cells assessed as growth inhibition after 3 days by SRB assay, IC50 = 0.10667 μM. 24529870
HCT116 Cytotoxicity assay Cytotoxicity against human HCT116 cells, IC50 = 0.166 μM. 24529870
MDA-MB-231 Cytotoxicity assay Cytotoxicity against human MDA-MB-231 cells, IC50 = 0.176 μM. 24529870
A549 Cytotoxicity assay Cytotoxicity against human A549 cells, IC50 = 0.259 μM. 24529870
HEK293 Cytotoxicity assay 72 hrs Intrinsic cytotoxicity against HEK293 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IG50 = 0.005 μM. 25272055
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.00428 μM. 25835359
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.01854 μM. 25835359
HCT15 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT15 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.008 μM. 27060760
U251 Cytotoxicity assay 72 hrs Cytotoxicity against human U251 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.021 μM. 27060760
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.03 μM. 27060760
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.054 μM. 27060760
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 0.515 μM. 27060760
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells assessed as growth inhibition after 72 hrs by SRB assay, IC50 = 1.97 μM. 27060760
NCI-H460 Cytotoxicity assay 24 hrs Cytotoxicity against human NCI-H460 cells pretreated for 24 hrs under normoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50 = 0.05 μM. 28350997
NCI-H460 Cytotoxicity assay 24 hrs Cytotoxicity against human NCI-H460 cells pretreated for 24 hrs under hypoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50 = 0.06 μM. 28350997
HT-29 Cytotoxicity assay 24 hrs Cytotoxicity against human HT-29 cells pretreated for 24 hrs under normoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50 = 2.74 μM. 28350997
HT-29 Cytotoxicity assay 24 hrs Cytotoxicity against human HT-29 cells pretreated for 24 hrs under hypoxic condition followed by compound washout measured after 72 hrs by MTT assay, IC50 = 3.71 μM. 28350997
NCI-H460 Cytotoxicity assay 72 hrs Cytotoxicity against human NCI-H460 cells assessed as growth reduction under hypoxic condition after 72 hrs by MTT assay, IC50 = 0.047 μM. 28740613
NCI-H460 Cytotoxicity assay 72 hrs Cytotoxicity against human NCI-H460 cells assessed as growth reduction under normoxic condition after 72 hrs by MTT assay, IC50 = 0.05 μM. 28740613
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as growth reduction under normoxic condition after 72 hrs by MTT assay, IC50 = 0.096 μM. 28740613
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as growth reduction under hypoxic condition after 72 hrs by MTT assay, IC50 = 0.119 μM. 28740613
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 0.00078 μM. 30115492
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by SRB assay, IC50 = 0.00162 μM. 30115492
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.0001 μM. 30169038
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.2 μM. 30169038
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 19 mg/mL (48.41 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
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In vivo Formulation Calculator (Clear solution)

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Chemical Information, Storage & Stability

Molecular Weight 392.4 Formula

C22H20N2O5

 Storage (From the date of receipt)
CAS No. 86639-52-3 Download SDF Storage of Stock Solutions

Synonyms NK012 Smiles CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)O

Mechanism of Action

Targets/IC50/Ki
Topo I
(Cell-free assay)
In vitro

SN-38, a biological active metabolite of  CPT-11. This compound 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 this compound and CPT shows no effect on the position of relaxed DNA. It dose-dependently and time-dependently inhibit DNA synthesis. Respective IC50 values of this chemical, in DNA synthesis is 0.077 μM. The inhibitory effect of it on RNA synthesis is less than that on DNA synthesis and it does not inhibit protein synthesis. This metabolite caused frequent DNA single-strand breaks in P388 cells.

Kinase Assay
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 CHQ, 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.
In vivo

After oral dosing, peak concentrations of this compound occur within 1 h, and the percent unbound 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%. Lactone AUCs in mice bearing human neuroblastoma xenografts are greater than in nontumor-bearing animals.

References
  • [4] https://pubmed.ncbi.nlm.nih.gov/30587986/

Applications

Methods Biomarkers Images PMID
Western blot p-Chk1 / Chk1 / Topo I
S4908-WB1
18509065
Growth inhibition assay Cell viability
S4908-viability1
25759163

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06143774 Recruiting
Advanced Solid Tumor
TaiRx Inc.
 October 31 2023 Phase 1
NCT05101096 Recruiting
Advanced Solid Tumor|Metastatic Triple-Negative Breast Cancer|HR+/HER2- Metastatic Breast Cancer|Metastatic Urothelial Cancer
Gilead Sciences
 October 20 2021 Phase 1|Phase 2
NCT05119907 Recruiting
Solid Tumor
Gilead Sciences
 October 12 2021 Phase 2
NCT04866641 Recruiting
Advanced Solid Tumor
Taivex Therapeutics Corporation
 June 24 2021 Phase 1
NCT04617522 Recruiting
Advanced or Metastatic Solid Tumor|Liver Failure
Gilead Sciences
 April 6 2021 Phase 1

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