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

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.99%

99.99

Verwandte Targets	HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase Casein Kinase
Andere CDK Inhibitors	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

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien	Assay-Typ	Inkubationszeit	Aktivitätsbeschreibung	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
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht	382.24	Formel	C₁₆H₁₇Cl₂N₅O₂	Lagerung (Ab Erhaltdatum)	3 Jahre-20°CPulver
CAS-Nr.	844442-38-2	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	AT7519M			Smiles	C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 10 mg/mL (26.16 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 25 mg/mL (65.4 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewicht-Rechner

In vivo Charge:
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 Von Selleck-Laboren validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, wenden Sie sich für kundenspezifische Tests an unser Vertriebsteam.	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-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

Dosierung: mg/kg Durchschnittliches Gewicht der Tiere: g Dosierungsvolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, nicht die Formulierung. Bitte kontaktieren Sie uns zuerst, wenn im Abschnitt Löslichkeit keine In-vivo-Formulierung angegeben ist.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammflüssigkeit: mg Wirkstoff voraufgelöst in μL DMSO ( Konzentration der Stammflüssigkeit mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der jeweiligen Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzuμL PEG300, mischen und aufklären, fügen Sie als Nächstes hinzuμL Tween 80, mischen und aufklären, fügen Sie als Nächstes hinzu μL ddH₂O, mischen und aufklären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzu μL Maisöl, mischen und aufklären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, die Lösungsmittel in der richtigen Reihenfolge hinzuzufügen. Sie müssen sicherstellen, dass die im vorherigen Schritt erhaltene Lösung klar ist, bevor Sie das nächste Lösungsmittel hinzufügen. Physikalische Methoden wie Vortexen, Ultraschall oder ein warmes Wasserbad können zur Unterstützung des Lösungsvorgangs verwendet werden.

Wirkungsmechanismus (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 an ATP competitive CDK inhibitor with a K_i value of 38 nM for CDK1. This compound is inactive against all non-CDK kinases with the exception of GSK3β (IC50 = 89 nM). It shows potent antiproliferative activity in a variety of human tumor cell lines with IC50 values ranging from 40 nM for MCF-7 to 940 nM for SW620 consistent with the inhibition of CDK1 and CDK2. This chemical induces dose-dependent cytotoxicity in multiple myeloma (MM) cell lines with IC50 values ranging from 0.5 to 2 μM at 48 hours, with the most sensitive cell lines being MM.1S (0.5 μM) and U266 (0.5 μM) and the most resistant MM.1R (>2 μM). It does not induce cytotoxicity in peripheral blood mononuclear cells (PBMNC). This inhibitor partially overcomes the proliferative advantage conferred by IL6 and IGF-1 as well as the protective effect of bone marrow stromal cells (BMSCs). It induces rapid dephosphorylation of RNA pol II CTD at serine 2 and serine 5 sites, and leads to the inhibition of transcription, partially contributing to its induced cytotoxicity of MM cells. This agent induces activation of GSK-3β by down-regulating GSK-3β phosphorylation, which also contributes to its induced apoptosis independent of the inhibition of transcription.
Kinase-Assay	In-vitro-Kinase-Assays
Kinase-Assay	In-vivo-Studien
In vivo	A twice daily dosing of AT7519 (9.1 mg/kg) causes tumor regression of both early-stage and advanced-stage s.c. tumors in the HCT116 and HT29 colon cancer xenograft models. This compound treatment (15 mg/kg) inhibits tumor growth and prolongs the median overall survival of mice in the human MM xenograft mouse model in association with increased caspase 3 activation.
Referenzen	[1] https://pubmed.ncbi.nlm.nih.gov/19174555/ [2] https://pubmed.ncbi.nlm.nih.gov/20101221/

Anwendungen (Applications)

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

Informationen zu klinischen Studien (Clinical Trial Information)

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Bedingungen	Sponsor/Kollaboratoren	Startdatum	Phases
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 Inhibitor

Molekulargewicht: 382.24

Qualitätskontrolle (Quality Control)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkungsmechanismus (Mechanism of Action)

Anwendungen (Applications)

Informationen zu klinischen Studien (Clinical Trial Information)

AT7519 CDK Inhibitor

Molekulargewicht: 382.24

Qualitätskontrolle (Quality Control)

Zellkultur, Behandlung & Arbeitskonzentration (Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkungsmechanismus (Mechanism of Action)

Anwendungen (Applications)

Informationen zu klinischen Studien (Clinical Trial Information)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)