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SN-38 Topoisomerase I-remmer

Name: SN-38
Brand: Selleck Chemicals
SKU: S4908
Rating: 5 (101 reviews)

Cat.Nr.S4908

SN-38 (NK012) is een actieve metaboliet van CPT-11, remt DNA topoisomerase I, DNA-synthese en veroorzaakt frequent DNA-enkelstrengsbreuken. SN-38 induceert autophagy.

SN-38 ADC Cytotoxin Remmer Chemical Structure

Chemische structuur

Moleculair gewicht: 392.4

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.96%

99.96

Gerelateerde doelwitten	HDAC PARP ATM/ATR DNA-PK WRN DNA/RNA Synthesis Topoisomerase PPAR Sirtuin Casein Kinase
Overige ADC Cytotoxin Inhibitoren	Triptolide Luteolin (+)-Bicuculline Rutin Artemisinin BHQ Pinocembrin Luteoloside Sacituzumab-govitecan Lappaconite HBr

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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
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Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	392.4	Formule	C₂₂H₂₀N₂O₅	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	86639-52-3	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	NK012			Smiles	CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)O

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 19 mg/mL (48.41 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 50 mg/mL (127.42 mM) Verwarmd met 50°C waterbad; Geultrasoneerd;
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.630mg/ml (1.61mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	Topo I (Cell-free assay)
In vitro	SN-38, een biologisch actieve metaboliet van CPT-11. Deze verbinding veroorzaakt de sterkste remming van DNA topoisomerase I, gevolgd door CPT en vervolgens CPT-11. CPT-11 verschuift dosisafhankelijk de positie van ontspannen DNA in de richting van ingeknipt DNA, maar deze verbinding en CPT hebben geen effect op de positie van ontspannen DNA. Het remt dosis- en tijdafhankelijk de DNA-synthese. Respectieve IC50-waarden van deze chemische stof, bij DNA-synthese, zijn 0,077 μM. Het remmende effect ervan op RNA-synthese is minder dan dat op DNA-synthese en het remt de eiwitsynthese niet. Deze metaboliet veroorzaakte frequente DNA-enkelstrengsbreuken in P388-cellen.
Kinase Assay	Topoisomerase I-analyse
Kinase Assay	Een eenheid (de minimale hoeveelheid voor volledige relaxatie van 0,5 μg SV40 DNA onder de omstandigheden van deze studie) van topoisomerase I, 0,5 μL van de testverbindingen en 0,5 μg SV40 DNA worden sequentieel toegevoegd aan de reactiebuffer, die is samengesteld uit 25 mM Tris-HCl (pH 7,5), 50 mM KCl, 5 mM MgCl₂, 0,25 mM EDTA dinatriumzout, 0,25 mM dithiothreitol, 15 μg/mL runder serumalbumine en 5% glycerol. Vervolgens wordt het reactiemengsel (50 μL) gedurende 10 min bij 37 °C geïncubeerd en de reactie wordt beëindigd door behandeling met 7,5 μL van een oplossing bestaande uit 1% natriumdodecylsulfaat, 20 mM EDTA dinatriumzout en 0,5 mg/mL proteinase K gedurende nog eens 30 min bij 37 °C. De monsters worden gemengd met 5 μL van de laadbuffer die 10 mM Na₂HPO₄, 31,3% sucrose en 0,3% broomfenolblauw bevat. Ontspannen (vorm Ir) DNA wordt gescheiden van supercoiled (vorm I) en ingeknipt (vorm II) DNA door elektroforese op 0,8% agarosegel bij 50 mA en 20 V gedurende 17 uur in aanwezigheid van 2 μg/mL CHQ, 10 mM EDTA, 30 mM NaH₂PO₄ en 36 mM Tris-HCl (pH 7,8). Na elektroforese wordt de gel gekleurd met 0,05% ethidiumbromide en gefotografeerd met UV-licht (302 nm). De hoeveelheid DNA wordt gekwantificeerd met behulp van een densitometer.
In vivo	Na orale toediening treden piekconcentraties van deze verbinding op binnen 1 uur, en het percentage ongebonden lacton in muizenplasma bij 1000 ng/mL is 3,4 +/- 0,67%, terwijl bij 100 ng/mL het percentage ongebonden 1,18 +/- 0,14% is. Lacton-AUC's bij muizen met humane neuroblastoomxenografts zijn groter dan bij dieren zonder tumor.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/1651156/ [2] http://www.ncbi.nlm.nih.gov/pubmed/ 9219511 [3] https://pubmed.ncbi.nlm.nih.gov/12712458/ [4] https://pubmed.ncbi.nlm.nih.gov/30587986/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-Chk1 / Chk1 / Topo I		18509065
Growth inhibition assay	Cell viability		25759163

Informatie klinische proef (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):