Name: AT7519
Brand: Selleck Chemicals
SKU: S1524
Rating: 5 (54 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase Casein Kinase
Overige CDK Inhibitoren	AS2863619 Ro-3306 SEL120 (SEL120-34A) hydrochloride INX-315 Tagtociclib (PF-07104091) PF-07220060 (CDK4/6-IN-6) AZD4573 ON123300 Enitociclib (BAY 1251152) Samuraciclib (ICEC0942) hydrochloride

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

Cellijnen	Assaytype	Incubatietijd	Activiteitsbeschrijving	PMID
HCT116	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCT116 cells assessed as cell viability after 72 hrs by alamar blue assay, IC50=0.082μM	18656911
A2780	Antiproliferative assay	72 hrs	Antiproliferative activity against human A2780 cells assessed as cell viability after 72 hrs by alamar blue assay, IC50=0.35μM	18656911
MRC5	Antiproliferative assay	72 hrs	Antiproliferative activity against human MRC5 cells assessed as cell viability after 72 hrs by alamar blue assay, IC50=0.98μM	18656911
HCT116	Function assay		Inhibition of CDK1 in human HCT116 cells assessed as PP1-alpha(Thr320) phosphorylation	18656911
HCT116	Function assay		Inhibition of CDK2 in human HCT116 cells assessed as Rb(Thr321) phosphorylation	18656911
HCT116	Function assay		Inhibition of CDK2 in human HCT116 cells assessed as NPM(Thr199) phosphorylation	18656911
HCT116	Cytotoxicity assay	72 hrs	Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by Alamar blue assay, IC50=0.08μM	26115571
Sf21	Function assay		Inhibition of recombinant human full length N-terminal His6-tagged CDK5/N-terminal GST-tagged p25 expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.018μM	27171036
Sf21	Function assay		Inhibition of human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin A expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.044μM	27171036
sf cells	Function assay		Inhibition of recombinant human N-terminal GST-tagged CDK4/cyclin D1 expressed in baculovirus infected sf cells, Ki=0.067μM	27171036
Sf21	Function assay		Inhibition of recombinant human full length C-terminal His6-tagged CDK9/cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, Ki<0.1μM	27171036
Sf21	Function assay		Inhibition of human full length C-terminal His6-tagged CDK1/N-terminal GST-tagged cyclin B expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.19μM	27171036
Sf21	Function assay		Inhibition of recombinant human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin E expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, Ki=0.51μM	27171036
Sf21	Function assay		Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide, Ki=2.8μM	27171036
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC 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
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 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
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 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
HEI-OC1	Function assay		Protection against cisplatin-induced cell death in neonatal mouse HEI-OC1 cells assessed as reduction in caspase-3/7 activity, EC50=0.38μM	30091915
MIAPaCa2	Antiproliferative assay	72 hrs	Antiproliferative activity against human MIAPaCa2 cells after 72 hrs by prestoblue assay, IC50=0.411μM	30343954
AsPC1	Antiproliferative assay	72 hrs	Antiproliferative activity against human AsPC1 cells after 72 hrs by prestoblue assay, IC50=0.533μM	30343954
SUIT2	Antiproliferative assay	72 hrs	Antiproliferative activity against human SUIT2 cells after 72 hrs by prestoblue assay, IC50=0.557μM	30343954
BxPC3	Antiproliferative assay	72 hrs	Antiproliferative activity against human BxPC3 cells after 72 hrs by prestoblue assay, IC50=0.64μM	30343954
S2-013	Antiproliferative assay	72 hrs	Antiproliferative activity against human S2-013 cells after 72 hrs by prestoblue assay, IC50=2.77μM	30343954
Sf21	Function assay		Inhibition of recombinant human full-length C-terminal His6-tagged CDK9/human full-length untagged cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, IC50<0.01μM	30543440
Sf21	Function assay	2 hrs	Inhibition of recombinant full-length human C-terminal His6-tagged CDK1/human full-length N-terminal GST-tagged Cyclin B expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate measured after 2 hrs in presence of gamma[32P] ATP b, IC50=0.21μM	30543440
Sf21	Function assay		Inhibition of recombinant human full-length C-terminal His6-tagged CDK3/full-length human N-terminal GST-tagged Cyclin E expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, IC50=0.36μM	30543440
Sf21	Function assay		Inhibition of recombinant human C-terminal His6-tagged full length CDK7/untagged recombinant full length human Cyclin H/N-terminal GST-tagged recombinant full length human MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 peptide as subs, IC50=2.4μM	30543440
HCT116	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 72 hrs by cell titer glo-based luminescence assay, IC50=0.132μM	31175010
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	382.24	Formule	C₁₆H₁₇Cl₂N₅O₂	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	844442-38-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	AT7519M			Smiles	C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 10 mg/mL (26.16 mM)
(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.
Clear solution	2%DMSO 1 30%PEG300 2 2%Tween80 3 66%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.000mg/ml (2.62mM)	Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

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	CDK9/CyclinT (Cell-free assay) <10 nM CDK5/p35 (Cell-free assay) 13 nM CDK2/CyclinA (Cell-free assay) 47 nM GSK-3β (Cell-free assay) 89 nM CDK4/CyclinD1 (Cell-free assay) 100 nM CDK6/CyclinD3 (Cell-free assay) 170 nM CDK1/CyclinB (Cell-free assay) 210 nM CDK3/CyclinE (Cell-free assay) 360 nM
In vitro	AT7519 is een ATP-competitieve CDK-remmer met een K_i-waarde van 38 nM voor CDK1. Deze verbinding is inactief tegen alle niet-CDK-kinasen, met uitzondering van GSK3β (IC50 = 89 nM). Het vertoont een potente antiproliferatieve activiteit in een verscheidenheid aan menselijke tumorcellijnen met IC50-waarden variërend van 40 nM voor MCF-7 tot 940 nM voor SW620, consistent met de remming van CDK1 en CDK2. Deze chemische stof induceert dosisafhankelijke cytotoxiciteit in multiple myeloma (MM) cellijnen met IC50-waarden variërend van 0,5 tot 2 μM na 48 uur, waarbij de meest gevoelige cellijnen MM.1S (0,5 μM) en U266 (0,5 μM) zijn en de meest resistente MM.1R (>2 μM). Het induceert geen cytotoxiciteit in perifere bloedmononucleaire cellen (PBMNC). Deze remmer overwint gedeeltelijk het proliferatieve voordeel dat wordt verleend door IL6 en IGF-1, evenals het beschermende effect van beenmergstromale cellen (BMSC's). Het induceert een snelle defosforylering van RNA pol II CTD op serine 2- en serine 5-plaatsen, en leidt tot de remming van transcriptie, wat gedeeltelijk bijdraagt aan de geïnduceerde cytotoxiciteit van MM-cellen. Dit middel induceert activering van GSK-3β door down-regulatie van GSK-3β-fosforylering, wat ook bijdraagt aan de geïnduceerde Apoptosis related, onafhankelijk van de remming van transcriptie.
Kinase Assay	In vitro kinase assays
Kinase Assay	AT7519, een kleine molecule remmer van CDK, induceert apoptose door GSK-3 te remmen bij borstkankercellen.
In vivo	Een tweemaal daagse dosering van AT7519 (9,1 mg/kg) veroorzaakt tumorregressie van zowel vroegtijdige als gevorderde s.c. tumoren in de HCT116- en HT29-xenograftmodellen voor darmkanker. Deze verbindingbehandeling (15 mg/kg) remt tumorgroei en verlengt de mediane algehele overleving van muizen in het humane MM-xenograftmuismodel in verband met verhoogde caspase 3-activering.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/19174555/ [2] https://pubmed.ncbi.nlm.nih.gov/20101221/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Growth inhibition assay	Cell viability		20101221
Western blot	CDK1 / CDK2 / CDK4 / Cyclin B1 / Cyclin E / CDK9 / CDK5 / CDK6 / Cyclin D1 / Cyclin A		20101221

Informatie klinische proef (Clinical Trial Information)

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

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT01183949	Completed	Multiple Myeloma	Astex Pharmaceuticals Inc.\|Multiple Myeloma Research Consortium	November 2010	Phase 1\|Phase 2

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):

AT7519 CDK Remmer

Chemische structuur

Moleculair gewicht: 382.24

Kwaliteitscontrole (Quality Control)

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

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

AT7519 CDK Remmer

Chemische structuur

Moleculair gewicht: 382.24

Kwaliteitscontrole (Quality Control)

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

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

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