Home Cell Cycle CDK Inhibitor Flavopiridol (Alvocidib, HMR-1275)

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Flavopiridol (Alvocidib, HMR-1275) CDK Inhibitor

Kat.-Nr.: S1230

Flavopiridol (Alvocidib) konkurriert mit ATP, um CDKs zu hemmen, einschließlich CDK1, CDK2, CDK4, CDK6 und CDK9 mit IC50-Werten im Bereich von 20-100 nM. Es ist selektiver für CDK1, 2, 4, 6, 9 im Vergleich zu CDK7. Flavopiridol hemmt ursprünglich EGFR und PKA. Flavopiridol induziert autophagy und ER-Stress. Flavopiridol blockiert die HIV-1-Replikation. Phase 1/2.
Flavopiridol (Alvocidib, HMR-1275) CDK Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 401.84

Springe zu

Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.92%
99.92

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

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
MCF-7 tumor cell Proliferation assay Inhibition of MCF-7 tumor cell proliferation 10843211
PC3 cell Function assay Inhibition of PC3 cell clonogenic assay, IC50=10 μM 11063609
HCT116 cell Function assay Inhibition of HCT116 cell clonogenic assay, IC50=13 μM 11063609
A2780 cell Function assay Inhibition of A2780 cell clonogenic assay， IC50=15 μM 11063609
Mia PaCa-2 cell Function assay Inhibition of Mia PaCa-2 cell clonogenic assay, IC50=36 μM 11063609
LNCaP human prostate carcinoma cell Proliferation assay Inhibition of LNCaP human prostate carcinoma cell proliferation 12190313
HCT116/VP35 human colon carcinoma cell Proliferation assay Inhibition of HCT116/VP35 human colon carcinoma cell proliferation, IC50=17 nM 12190313
HCT116 human colon carcinoma cell Proliferation assay Inhibition of HCT116 human colon carcinoma cell proliferation, IC50=18 nM 12190313
HCT116/VM46 human colon carcinoma cell Proliferation assay Inhibition of HCT116/VM46 human colon carcinoma cell proliferation, IC50=21 nM 12190313
A2780/DDP-R human ovarian carcinoma cell Proliferation assay Inhibition of A2780/DDP-R human ovarian carcinoma cell proliferation, IC50=38 nM 12190313
ABAE human fibroblast cell Proliferation assay Inhibition of ABAE human fibroblast cell proliferation, IC50=45 nM 12190313
HL60 human leukemia cell Proliferation assay Inhibition of HL60 human leukemia cell proliferation, IC50=46 nM 12190313
Hs 27 human fibroblast cell Proliferation assay Inhibition of Hs 27 human fibroblast cell proliferation, IC50=51 nM 12190313
CCRF-CEM human leukemia cell Proliferation assay Inhibition of CCRF-CEM human leukemia cell proliferation, IC50=52 nM 12190313
OVCAR-3 human ovarian carcinoma cell Proliferation assay Inhibition of OVCAR-3 human ovarian carcinoma cell proliferation, IC50=54 nM 12190313
A2780/DDP-S human ovarian carcinoma cell Proliferation assay Inhibition of A2780/DDP-S human ovarian carcinoma cell proliferation, IC50=56 nM 12190313
A2780/TAX-S human ovarian carcinoma cell Proliferation assay Inhibition of A2780/TAX-S human ovarian carcinoma cell proliferation, IC50=65 nM 12190313
LS174T human colon carcinoma cell Proliferation assay Inhibition of LS174T human colon carcinoma cell proliferation, IC50=65 nM 12190313
MCF-7 human breast carcinoma cell Proliferation assay Inhibition of MCF-7 human breast carcinoma cell proliferation, IC50=66 nM 12190313
PC3 human prostate carcinoma cell Proliferation assay Inhibition of PC3 human prostate carcinoma cell proliferation, IC50=66 nM 12190313
MLF mouse lung fibroblast cell Proliferation assay Inhibition of MLF mouse lung fibroblast cell proliferation, IC50=72 nM 12190313
LX-1 human lung carcinoma Proliferation assay Inhibition of LX-1 human lung carcinoma proliferation, IC50=75 nM 12190313
A431 human squamous cell Proliferation assay Inhibition of A431 human squamous cell carcinoma cell proliferation, IC50=75 nM 12190313
SKBR-3 human breast carcinoma cell Proliferation assay Inhibition of SKBR-3 human breast carcinoma cell proliferation, IC50=77 nM 12190313
A2780/TAX-R human ovarian carcinoma cell Proliferation assay Inhibition of A2780/TAX-R human ovarian carcinoma cell proliferation, IC50=78 nM 12190313
M109 mouse lung carcinoma cell Proliferation assay Inhibition of M109 mouse lung carcinoma cell proliferation, IC50=80 nM 12190313
CACO-2 human colon carcinoma cell Proliferation assay Inhibition of CACO-2 human colon carcinoma cell proliferation, IC50=86 nM 12190313
A549 human lung carcinoma cell Proliferation assay Inhibition of A549 human lung carcinoma cell proliferation, IC50=96 nM 12190313
MIP human colon carcinoma cell Function assay Inhibition of MIP human colon carcinoma cell line, IC50=0.12 μM 12190313
K562 human leukemia cell Proliferation assay Inhibition of K562 human leukemia cell proliferation, IC50=0.13 μM 12190313
human A2780 cell line Proliferation assay 72 h Antiproliferative effect against human A2780 cell line was determined in a whole cell 72 hr cytotoxicity assay, IC50=71 nM 15027863
human ovarian (A2780) cancer cell Cytotoxic assay Cytotoxic effect on human ovarian (A2780) cancer cell line, IC50=71 nM 15125971
ID8 cells Proliferation assay Antiproliferative activity against ID8 cells, IC50=7 nM 17123821
MCF7 cells Proliferation assay Antiproliferative activity against MCF7 cells, IC50=26 nM 17123821
Sf9 cells Function assay Inhibition of recombinant cyclin A/CDK2 expressed in Sf9 cells, IC50=12 nM 17904366
human A2780 cells Function assay Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells 18469809
human A2780 cells Function assay 24 h Inhibition of cdk-mediated Rb phosphorylation at thr821 in human A2780 cells after 24 hrs 18469809
human NCI60 cells Proliferation assay 72 h Antiproliferative activity against human NCI60 cells after 72 hrs by sulforhodamine B assay, GI50=74.7 nM 21080703
human NCI60 cells Proliferation assay 72 h Antiproliferative activity against human NCI60 cells assessed as lethal effect after 72 hrs by sulforhodamine B assay, LC50=0.904 μM 21080703
human A2780 cells Cytotoxic assay 24 h Cytotoxicity against human A2780 cells after 24 hrs by MTT assay, GI50=23 nM 23301767
human MRC5 cells Cytotoxic assay 72 h Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay, GI50=28 nM 23301767
human A2780 cells Cytotoxic assay 72 h Cytotoxicity against human A2780 cells after 72 hrs by MTT assay, GI50=29 nM 23301767
human A2780 cells Cytotoxic assay 48 h Cytotoxicity against human A2780 cells after 48 hrs by MTT assay, GI50=31 nM 23301767
human MRC5 cells Cytotoxic assay 48 h Cytotoxicity against human MRC5 cells after 48 hrs by MTT assay, GI50=39 nM 23301767
human MRC5 cells Cytotoxic assay 24 h Cytotoxicity against human MRC5 cells after 24 hrs by MTT assay, GI50=49 nM 23301767
human HMEC1 cells Cytotoxic assay 24 h Cytotoxicity against human HMEC1 cells after 24 hrs by MTT assay, GI50=61 nM 23301767
human HMEC1 cells Cytotoxic assay 48 h Cytotoxicity against human HMEC1 cells after 48 hrs by MTT assay, GI50=62 nM 23301767
human HMEC1 cells Cytotoxic assay 72 h Cytotoxicity against human HMEC1 cells after 72 hrs by MTT assay, GI50=66 nM 23301767
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in sb-G1 after 24 hr r at 330 nM (IC50), Cell cycle = 0.001 μM. 12190313
A2780 Apoptosis assay 330 nM 24 hr Apoptotic A2780 cells after 24 hr r at 330 nM (IC50), Cell cycle = 0.001 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in sub-G1 after 24 hr r at 2980 nM (IC90), Cell cycle = 0.002 μM. 12190313
A2780 Apoptosis assay 2980 nM 24 hr Apoptotic A2780 cells after 24 hr r at 2980 nM (IC90), Cell cycle = 0.009 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in S-phase after 24 hr r at 2980 nM (IC90), Cell cycle = 0.012 μM. 12190313
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in S-phase after 24 hr r at 330 nM (IC50), Cell cycle = 0.016 μM. 12190313
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in G2/M after 24 hr r at 330 nM (IC50), Cell cycle = 0.023 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in G2/M after 24 hr r at 2980 nM (IC90), Cell cycle = 0.025 μM. 12190313
A2780 Function assay 330 nM 24 hr Percentage A2780 cells in G1 after 24 hr r at 330 nM (IC50), Cell cycle = 0.06 μM. 12190313
A2780 Function assay 2980 nM 24 hr Percentage A2780 cells in G1 after 24 hr r at 2980 nM (IC90), Cell cycle = 0.061 μM. 12190313
A2780 Function assay 24 hrs Inhibition of cdk-mediated Rb phosphorylation at ser807/811 in human A2780 cells after 24 hrs 18469809
A2780 Function assay 24 hrs Inhibition of cdk9-mediated RNA pol2 CTD phosphorylation at ser2 in human A2780 cells after 24 hrs 18469809
A2780 Function assay 24 hrs Inhibition of cdk7-mediated RNA pol2 CTD phosphorylation at ser5 in human A2780 cells after 24 hrs 18469809
A2780 Apoptosis assay 24 hrs Induction of apoptosis in human A2780 cells assessed as appearance of Mcl1 protein level after 24 hrs 18469809
DR-U2OS-GFP Function assay 0.1 uM 56 hrs Reduction of homologous recombination in human DR-U2OS-GFP cells expressing I-SceI nuclease assessed as reduction of RAD51 level at 0.1 uM after 56 hrs by immunoblotting 21417417
A2780 Function assay 24 hrs Inhibition of CDK9 in human A2780 cells assessed as reduction of RNAPII CTD phosphorylation at Ser2 at GI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Cell cycle assay 24 hrs Cell cycle arrest in human A2780 cells assessed as accumulation at G2/M phase at less than GI50 after 24 hrs by flow cytometric analysis 23301767
A2780 Function assay 24 hrs Inhibition of CDK9 in human A2780 cells assessed as downregulation of MCL1 at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Apoptosis assay 24 hrs Induction of apoptosis in human A2780 cells assessed as induction of PARP cleavage at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Function assay 24 hrs Inhibition of CDK9 in human A2780 cells assessed as downregulation of HDM2 at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
MT4 Antiproliferative assay Antiviral activity against Human immunodeficiency virus 1 NL 4-3 infected in MT4 cells measured on day 4 post infection by p24 assay, EC50 = 0.015 μM. 25914804
MT4 Cytotoxicity assay Cytotoxicity against human MT4 cells, IC50 = 0.067 μM. 25914804
Sf9 Function assay 15 mins Inhibition of CDK2/cyclin E1 (unknown origin) expressed in Sf9 insect cells using UlightCFFKNIVTPRTPPPSQGK-amide substrate after 15 mins by autoradiography, IC50 = 0.13 μM. 25914804
A549 Antiproliferative assay 3 days Antiproliferative activity against human A549 cells after 3 days by SRB method, GI50 = 0.14 μM. 25914804
DU145 Antiproliferative assay 3 days Antiproliferative activity against human DU145 cells after 3 days by SRB method, GI50 = 0.15 μM. 25914804
KB Antiproliferative assay 3 days Antiproliferative activity against human KB cells after 3 days by SRB method, GI50 = 0.16 μM. 25914804
KBVIN Antiproliferative assay 3 days Antiproliferative activity against human KBVIN cells after 3 days by SRB method, GI50 = 0.18 μM. 25914804
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Celltiter-Glo reagent based assay in presence of 10% fetal bovine serum, EC50 = 0.034 μM. 26985305
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Celltiter-Glo reagent based assay in presence of 0.625% fetal bovine serum, EC50 = 0.059 μM. 26985305
Sf9 Function assay 10 mins Inhibition of human His6-tagged CDK9/cyclin T1 expressed in baculovirus infected sf9 cells using GST-CTD as substrate after 10 mins in presence of [gamma-32P]ATP by SDS-PAGE analysis, IC50 = 0.0025 μM. 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, IC50 = 0.011 μM. 27171036
HeLa Cytotoxicity assay 72 hrs Cytotoxicity against human HeLa cells assessed as decrease in cell viability after 72 hrs by MTT assay, CC50 = 0.12 μM. 27171036
sf21 Function assay Inhibition of full length human N-terminal His6-tagged CDK6/N-terminal GST-tagged cyclin D3 expressed in sf21 cells using histone H1 substrate, IC50 = 0.395 μM. 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, IC50 = 0.514 μM. 27171036
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.1464 μM. 29407975
KOPN8 Antiproliferative assay 72 hrs Antiproliferative activity against human KOPN8 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.1926 μM. 29407975
SEM Antiproliferative assay 72 hrs Antiproliferative activity against human SEM cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.2043 μM. 29407975
UOCB1 Antiproliferative assay 72 hrs Antiproliferative activity against human UOCB1 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.2084 μM. 29407975
KOPN8 Apoptosis assay 0.5 uM 3 to 24 hrs Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM after 3 to 24 hrs by Western blot analysis 29407975
KOPN8 Apoptosis assay 0.5 uM 1 hr Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM pre-treated with NAC for 1 hr and measured after 3 to 24 hrs by Western blot analysis 29407975
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht 401.84 Formel

C21H20ClNO5

 Lagerung (Ab dem Eingangsdatum)
CAS-Nr. 146426-40-6 SDF herunterladen Lagerung von Stammlösungen

Synonyme NSC 649890, HMR-1275, L86-8275 Smiles CN1CCC(C(C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 80 mg/mL (199.08 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewichtsrechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

mg/kg g μL

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% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

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

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH2O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus (Mechanism of Action)

Merkmale
First CDK inhibitor to be used in human clinical trials.
Targets/IC50/Ki
CDK9
(Cell-free assay)
20 nM
CDK1
(Cell-free assay)
30 nM
CDK4
(Cell-free assay)
20-40 nM
CDK2
(Cell-free assay)
40 nM
CDK6
(Cell-free assay)
60 nM
CDK7
(Cell-free assay)
875 nM
In vitro
Flavopiridol (Alvocidib) displays less activity against unrelated kinases such as MAP, PAK, PKC, and EGFR with IC50 of >14 μM. It significantly inhibits the colony growth of HCT116, A2780, PC3, and Mia PaCa-2 cells with IC50 of 13 nM, 15 nM, 10 nM and 36 nM, respecitively. This compound also potently inhibits the activity of Glycogen synthase kinase-3 (GSK-3) with an IC50 of 280 nm. Compared with other CDKs, it inhibits the activity of CDK7 less potently with IC50 of 875 nM. At 0.5 μM, it inhibits both pSer807/811 Rb and pThr199 NPM, whereas mild changes are observed at pThr821 Rb. It also decreases the overall RNA polymerase II level, as well as the phosphorylation of RNA polymerase II on the CTD repeats at Ser2 Ser5. As a broad spectrum CDK inhibitor, it can inhibit cell cycle progression in either G1 or G2. At 0.3 μM, it induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. It exhibits potent cytotoxicity against a wide variety of tumor cell lines with IC50 values ranging form 16 nM for LNCAP to 130 nM for K562.
Kinase-Assay
CDK-Kinase-Assay
Für den CDK1/Cyclin B1-Kinase-Assay bestehen die Kinase-Reaktionen aus 100 ng des im Baculovirus exprimierten GST-CDK1/Cyclin B1 (human)-Komplexes, 1 μg Histon HI, 0,2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL Kinase-Puffer (50 mM Tris, pH 8,0, 10 mM MgCl2, 1 mM EGTA, 0,5 mM DTT). Für den CDK2/Cyclin E-Kinase-Assay bestehen die Kinase-Reaktionen aus 5 ng des im Baculovirus exprimierten GST-CDK2/Cyclin E (human)-Komplexes, 0,5 μg GST-RB-Fusionsprotein (Aminosäuren 776-928 des Retinoblastom-Proteins), 0,2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL Kinase-Puffer (50 mM Hepes, pH 8,0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). Für den CDK4/Cyclin D1-Kinase-Assay bestehen die Kinase-Reaktionen aus 150 ng des im Baculovirus exprimierten GST-CDK4/Cyclin D1 (human), 280 ng Stag-Cyclin D1, 0,5 μg GST-RB-Fusionsprotein (Aminosäuren 776-928 des Retinoblastom-Proteins), 0,2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL Kinase-Puffer (50 mM Hepes, pH 8,0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). Die Reaktionen werden 45 Minuten für CDK1 und CDK2 oder 1 Stunde für CDK4 bei 30 °C inkubiert und durch Zugabe von kalter Trichloressigsäure (TCA) bis zu einer Endkonzentration von 15 % gestoppt. TCA-Präzipitate werden auf GF/C-Unifilterplatten mit einem Filtermate Universal Harvester gesammelt und die Filter mit einem TopCount 96-Well Flüssigkeitsszintillationszähler quantifiziert. Flavopiridol (Alvocidib) wird in 10 mM in Dimethylformamid (DMF) gelöst und in sechs Konzentrationen, jeweils dreifach, evaluiert. Die Endkonzentration von DMF im Assay beträgt 2 %. Die IC50-Werte werden durch nichtlineare Regressionsanalyse abgeleitet und haben einen Variabilitätskoeffizienten von 16 %. Zur Bestimmung seiner Aktivität auf CDK6 wird ein Filterbindungsassay etabliert. Die folgenden Komponenten werden in der Reaktionsmischung kombiniert: 2 μL CDK6 (0,7 mg/μL), 5 μL Histon H1 (6 mg/mL), 14 μL Kinase-Puffer (60 mM β-Glycerophosphat, 30 mM p-Nitrophenylphosphat, 25 mM MOPS (pH 7,0), 5 mM EGTA, 15 mM MgCl2, 1 mM DTT, 0,1 mM Na-Vanadat), 3 μL zunehmender Konzentrationen dieser in 50 % DMSO verdünnten Verbindung und 6 μL 33P-ATP (1 mCi/mL) in nichtradioaktivem ATP bei 90 μM Konzentration (Endkonzentration: 15 μM). Der Assay wird durch Zugabe von 33P-ATP initiiert. Die Reaktion wird 20 Minuten bei 30 °C inkubiert. Ein 25 μL Aliquot des Überstands wird dann auf Whatman P81 Phosphocellulose-Papier aufgetragen. Die Filter werden 5 Mal mit 1 %iger Phosphorsäurelösung gewaschen. Feuchte Filter werden in Gegenwart von 1 mL Szintillationsflüssigkeit gezählt. Die Cdk9-Aktivität wird unter Verwendung von 50 nM rekombinantem Cdk9/Cyclin T in 50 mM HEPES pH 7,5, 10 mM MgCl2, 1 mM DTT, 3 μM Na3VO4, 150 μM RNA-Polymerase CDT-Peptid und 80 μM ATP gemessen. Der Cdk7-Assay wird im selben Puffer unter Verwendung von 37 nM gereinigter Kinase in Gegenwart von 200 μM ATP und 10 μM Myelin-Bindungsprotein als Substrat durchgeführt. Die Wirksamkeit gegenüber CDK9 und CDK7 wird entweder mittels eines starken Anionenaustauscher-(Dowex 1-X8 Harz, Formiat-Form)-basierten Assays oder eines Szintillationsproximity-Assays bestimmt. Die IC50-Werte werden aus den Dosis-Wirkungs-Kurven berechnet.
In vivo
Administration of S1230 at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, resulting in %T/C value of 110, and active against the human A2780 ovarian carcinoma implanted sc in nude mice, producing 1.5 log cell kill (LCK). S1230 treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. In the p21-intact Hct116 xenografts in nude mice, administration of CPT-11 (100 mg/kg) followed by S1230 (3 mg/kg) 7 and 16 hours later significantly inhibits tumor regression by 86% and 82%, respectively, displaying >2 fold inhibition compared with CPT-11 alone by 40 %. The combination produces ~30% complete response rate (CR) in contrast to CPT-11 alone where no CR is found.
Literatur
  • [4] https://pubmed.ncbi.nlm.nih.gov/8674031/
  • [5] https://pubmed.ncbi.nlm.nih.gov/12190313/
  • [6] https://pubmed.ncbi.nlm.nih.gov/18209094/
  • [7] https://pubmed.ncbi.nlm.nih.gov/11751522/
  • [8] https://pubmed.ncbi.nlm.nih.gov/18469809/
  • [9] https://pubmed.ncbi.nlm.nih.gov/11311660/

Anwendungen (Applications)

Methoden Biomarker Bilder PMID
Western blot Cleaved caspase-8 / Cleaved caspase-9 / Cleaved caspase-3 p-RNAPII / p-eIF4E / Mnk1 p-ERK / ERK / p-p38 / p-4EBP1 / 4EBP1 / p-S6 CDK2 / CDK4 / Cyclin A / p21 / p27 / Rb
S1230-WB1
31193061
Growth inhibition assay Cell viability
S1230-viability1
31193061

Klinische Studieninformationen (Clinical Trial Information)

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

NCT-Nummer Rekrutierung Erkrankungen Sponsor/Kooperationspartner Startdatum Phasen
NCT03441555 Completed
Acute Myeloid Leukemia (AML)
AbbVie|Sumitomo Pharma America Inc.
 May 30 2018 Phase 1
NCT03298984 Completed
Acute Myeloid Leukemia
Sumitomo Pharma America Inc.
 September 25 2017 Phase 1