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

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Flavopiridol (Alvocidib, HMR-1275) CDK Hämmare

Kat.nr.: S1230

Flavopiridol (Alvocidib) tävlar med ATP för att hämma CDK inklusive CDK1, CDK2, CDK4, CDK6 och CDK9 med IC50-värden i intervallet 20-100 nM. Det är mer selektivt för CDK1, 2, 4, 6, 9 jämfört med CDK7. Flavopiridol upptäcktes initialt hämma EGFR och PKA. Flavopiridol inducerar Autophagy och ER-stress. Flavopiridol blockerar HIV-1-replikation. Fas 1/2.
Flavopiridol (Alvocidib, HMR-1275) CDK Hämmare Chemical Structure

Kemisk struktur

Molekylvikt: 401.84

Hoppa till

Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.92%
99.92

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer Analystyp Koncentration Inkubationstid Formulering Aktivitetsbeskrivning 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
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt 401.84 Formel

C21H20ClNO5

 Lagring (från mottagningsdatumet)
CAS-nr 146426-40-6 Ladda ner SDF Lagring av stamlösningar

Synonymer 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

Löslighet (Solubility)

In vitro
Batch:

DMSO : 80 mg/mL (199.08 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa Koncentration Volym Molekylvikt
Utspädningsräknare Molekylviktsräknare

In vivo
Batch:

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

mg/kg g μL

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH2O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Egenskaper
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.
Kinasanalys
CDK-kinasanalys
För CDK1/cyclin B1-kinasanalys består kinasreaktioner av 100 ng av baculovirus-uttryckt GST-CDK1/cyclin B1 (humant) komplex, 1 μg histon HI, 0.2 μCi [γ-33P]ATP, 25 μM ATP i 50 μL kinasbuffert (50 mM Tris, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 0.5 mM DTT). För CDK2/cyclin E-kinasanalys består kinasreaktioner av 5 ng av baculovirus-uttryckt GST-CDK2/cyclin E (humant) komplex, 0.5 μg GST-RB fusionsprotein (aminosyror 776-928 av retinoblastomprotein), 0.2 μCi [γ-33P]ATP, 25 μM ATP i 50 μL kinasbuffert (50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). För CDK4/cyclin D1-kinasanalys består kinasreaktioner av 150 ng av baculovirus-uttryckt GST-CDK4/cyclin D1 (humant), 280 ng av Stag-cyclin D1, 0.5 μg GST-RB fusionsprotein (aminosyror 776-928 av retinoblastomprotein), 0.2 μCi [γ-33P]ATP, 25 μM ATP i 50 μL kinasbuffert (50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). Reaktionerna inkuberas i 45 minuter för CDK1 och CDK2, eller 1 timme för CDK4 vid 30 °C och stoppas genom tillsats av kall triklorättiksyra (TCA) till en slutkoncentration på 15 %. TCA-fällningar samlas upp på GF/C unifilter-plattor med en Filtermate universal skördare och filtren kvantifieras med en TopCount 96-brunns vätskescintillationsräknare. Flavopiridol (Alvocidib) löses vid 10 mM i dimetylformamid (DMF) och utvärderas i sex koncentrationer, var och en i triplikat. Slutkoncentrationen av DMF i analysen = 2 %. IC50-värden härleds genom icke-linjär regressionsanalys och har en variationskoefficient = 16 %. För att analysera dess aktivitet på CDK6 upprättas en filterbindningsanalys. Följande kombineras i reaktionsblandningen: 2 μL CDK6 (0,7 mg/μL), 5 μL histon H1 (6 mg/mL), 14 μL kinasbuffert (60 mM β-glycerofosfat, 30 mM p-nitrofenylfosfat, 25 mM MOPS (pH 7,0), 5 mM EGTA, 15 mM MgCl2, 1 mM DTT, 0,1 mM Na-vanadat), 3 μL ökande koncentrationer av denna förening utspädd i 50 % DMSO, och 6 μL 33P-ATP (1 mCi/mL) i icke-radioaktivt ATP vid 90 μM koncentration (slutkoncentration: 15 μM). Analysen initieras genom tillsats av 33P-ATP. Reaktionen inkuberas i 20 minuter vid 30 °C. En 25 μL alikvot av supernatanten punktas sedan på Whatman P81 fosfocellulosapapper. Filter tvättas 5 gånger med 1 % fosforsyralösning. Våta filter räknas i närvaro av 1 mL scintillationsvätska. Cdk9-aktivitet mäts med användning av 50 nM rekombinant Cdk9/cyclin T i 50 mM HEPES pH 7,5, 10 mM MgCl2, 1 mM DTT, 3 μM Na3VO4, 150 μM RNA-polymeras CDT-peptid och 80 μM ATP. Cdk7-analys utförs i samma buffert med 37 nM renat kinas i närvaro av 200 μM ATP och 10 μM myelinbasiskt protein som substrat. Dess potens mot CDK9 och CDK7 bestäms med användning av antingen en stark anjonbytare (Dowex 1-X8 harts, formatform)-baserad analys eller en scintillationsnärhetsanalys (scintillation proximity assay). IC50-värden beräknas från dos-responskurvorna.
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.
Referenser
  • [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/

Applikationer (Applications)

Metoder Biomarkörer 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

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer Rekrytering Tillstånd Sponsor/Samarbetspartners Startdatum Faser
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