Search results for: Caspase 5 Inhibitor Drug Screening Kit
#27512117 2016/09/16 Save this To Up
BPR1J373, an Oral Multiple Tyrosine Kinase Inhibitor, Targets c-KIT for the Treatment of c-KIT-Driven Myeloid Leukemia.Acute myelogenous leukemia (AML) carrying t(8;21)(q22;q22) or inv(16)/t(16;16)(p13;q22) is classified as core binding factor (CBF)-AML and accounts for approximately 15% of AML. c-KIT mutation can be detected in 17%∼46% of CBF-AML and is associated with poor prognosis. c-KIT mutation is a crucial hit and cooperates with AML1-ETO resulting from t(8;21)(q22;q22) to cause overt AML. Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used successfully to treat c-KIT driven gastrointestinal stromal tumors. However, the effect of TKI on c-KIT-driven leukemia, including CBF-AML and systemic mastocytosis (SM), has not been satisfactory. BPR1J373 is a 5-phenylthiazol-2-ylamine-pyriminide derivative targeting multiple tyrosine kinases. It was shown to inhibit cell proliferation and induce apoptosis in AML cells with constitutively activated c-KIT via inhibiting c-KIT phosphorylation and its downstream signals. The compound induced apoptosis by the mitochondrial intrinsic pathway through upregulation of proapoptotic proteins Bax and Bak and caspase 8 and 9 activation in c-KIT mutant Kasumi-1 cells. Furthermore, it induced cell-cycle arrest via targeting aurora kinase B in c-KIT wild-type KG-1 cells. The antitumor response of BPR1J373 was also shown in subcutaneously grafted SCID mice. BPR1J373 was shown to effectively suppress c-KIT phosphorylation of D816V mutation by treating c-KIT-null COS-1 cells transfected with c-KIT D816V mutant plasmid. In conclusion, BPR1J373 inhibits cell proliferation of c-KIT-driven AML cells via induction of apoptosis and cell-cycle arrest. It is also effective for multiple drug-resistant c-KIT D816V mutation. BPR1J373 deserves further development for clinical use in c-KIT-driven myeloid leukemia. Mol Cancer Ther; 15(10); 2323-33. ©2016 AACR.
2238 related Products with: BPR1J373, an Oral Multiple Tyrosine Kinase Inhibitor, Targets c-KIT for the Treatment of c-KIT-Driven Myeloid Leukemia.Cultrex In Vitro Angiogen Mouse ALK tyrosine kinase Human Lemur Tyrosine Kina Biotin Blocking Kit for Biotin Blocking Kit for CRF Anti-Polyvalent HRP Blue Feulgen DNA Ploidy PolyTek HRP Anti-Rabbit HIV 1 p24 antigen ELISA SIV p27 antigen ELISA HIV 1 p24 Antigen ELISA Amplite™ Fluorimetric F
#27035222 2016/05/09 Save this To Up
Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in human osteosarcoma cell line MG‑63 through the ROS/JNK signaling pathway.The present study was carried out to investigate the effect and mechanisms of aloe‑emodin (AE)-mediated photodynamic therapy (AE-PDT) on the human osteosarcoma cell line MG-63. After treatment with AE-PDT, the human osteosarcoma cell line MG-63 was tested for levels of viability, autophagy, reactive oxygen species (ROS) and apoptosis and changes in cell morphology with the Cell Counting Kit-8 (CCK‑8), monodansylcadaverine (MDC) and Hoechst staining and transmission electron microscopy. The expression of proteins including LC-3, cleaved caspase-3, Beclin-1, Bcl-2, p-JNK, t-JNK and β-actin was examined with western blotting. AE-PDT significantly inhibited the viability of the MG-63 cells in an AE-concentration- and PDT energy density-dependent manner. Autophagy and apoptosis of MG-63 cells was substantially promoted in the AE-PDT group compared to the control group, the AE alone group and the light emitting diode (LED) alone group. Inhibition of autophagy by 3-methyladenine (3-MA) (5 mM) and chloroquine (CQ) (15 µM) significantly promoted the apoptosis rate and improved the sensitivity of the MG-63 cells to AE-PDT. AE-PDT was found to induce the expression of ROS and p-JNK. ROS scavenger, N-acetyl-L-cysteine (NAC, 5 mM), was able to hinder the autophagy, apoptosis and phosphorylation of JNK, and JNK inhibitor (SP600125, 10 µM) significantly inhibited the autophagy and apoptosis, and attenuated the sensitivity of MG63 cells to AE-PDT. In conclusion, AE-PDT induced the autophagy and apoptosis of human osteosarcoma cell line MG-63 through the activation of the ROS-JNK signaling pathway. Autophagy may play a protective role during the early stage following treatment of AE-PDT.
2570 related Products with: Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in human osteosarcoma cell line MG‑63 through the ROS/JNK signaling pathway.AP-1 Reporter – HEK293 anti SLAM anti CDw150 IgG Macrophage Colony Stimula Wnt Signaling Pathway TCF T-Cell Receptor Signaling anti HSV (II) gB IgG1 (mo anti CD37 IgG2b (monoclon CELLKINES Natural Human I T-cell proliferation grad TCHI T cell proliferation TCHI T cell proliferation Jurkat Cell Extract (Indu
#25758415 2015/03/25 Save this To Up
3-(Benzo[d][1,3]dioxol-5-ylamino)-N-(4-fluorophenyl)thiophene-2-carboxamide overcomes cancer chemoresistance via inhibition of angiogenesis and P-glycoprotein efflux pump activity.3-((Quinolin-4-yl)methylamino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide (OSI-930, 1) is a potent inhibitor of c-kit and VEGFR2, currently under phase I clinical trials in patients with advanced solid tumors. In order to understand the structure-activity relationship, a series of 3-arylamino N-aryl thiophene 2-carboxamides were synthesized by modifications at both quinoline and amide domains of the OSI-930 scaffold. All the synthesized compounds were screened for in vitro cytotoxicity in a panel of cancer cell lines and for VEGFR1 and VEGFR2 inhibition. Thiophene 2-carboxamides substituted with benzo[d][1,3]dioxol-5-yl and 2,3-dihydrobenzo[b][1,4]dioxin-6-yl groups 1l and 1m displayed inhibition of VEGFR1 with IC50 values of 2.5 and 1.9 μM, respectively. Compounds 1l and 1m also inhibited the VEGF-induced HUVEC cell migration, indicating its anti-angiogenic activity. OSI-930 along with compounds 1l and 1m showed inhibition of P-gp efflux pumps (MDR1, ABCB1) with EC50 values in the range of 35-74 μM. The combination of these compounds with doxorubicin led to significant enhancement of the anticancer activity of doxorubicin in human colorectal carcinoma LS180 cells, which was evident from the improved IC50 of doxorubicin, the increased activity of caspase-3 and the significant reduction in colony formation ability of LS180 cells after treatment with doxorubicin. Compound 1l showed a 13.8-fold improvement in the IC50 of doxorubicin in LS180 cells. The ability of these compounds to display dual inhibition of VEGFR and P-gp efflux pumps demonstrates the promise of this scaffold for its development as multi-drug resistance-reversal agents.
2442 related Products with: 3-(Benzo[d][1,3]dioxol-5-ylamino)-N-(4-fluorophenyl)thiophene-2-carboxamide overcomes cancer chemoresistance via inhibition of angiogenesis and P-glycoprotein efflux pump activity.Directed In Vivo Angiogen 3-Amino-5-[4-(morpholin-4 (1S,3R)-1-Benzo[1,3]dioxo Mouse Anti-Lipoprotein Li Benzo(b)thiophene 2 boron EpiQuik Histone Methyltra EpiQuik Histone Methyltra EpiQuik Histone Methyltra EpiQuik Histone Methyltra EpiQuik Histone Methyltra EpiQuik Histone Methyltra EpiQuik MBD2 Binding Acti
#25528169 2015/04/28 Save this To Up
Sequential combination therapy with flavopiridol and autocatalytic caspase-3 driven by amplified hTERT promoter synergistically suppresses human ovarian carcinoma growth in vitro and in mice.Induction of cell apoptosis and regulation of cell cycle are very attractive for treatments of tumors including ovarian carcinoma. Flavopiridol is a potent small molecular cyclin-dependent kinase(cdk) inhibitor, but its antitumor efficacy is not satisfied yet. Caspase-3 play a major role in the transduction of apoptotic signals and the execution of apoptosis in mammalian cells. We have successfully constructed the recombinant adenovirues AdHTVP2G5-rev-casp3 containing autocatalytic caspase-3 (rev-caspase-3) driven by amplified hTERT promoter system (TSTA-hTERTp). In this study, we applied it with flavopiridol to investigate their antitumor effect on ovarian cancer in vitro and in vivo.
2104 related Products with: Sequential combination therapy with flavopiridol and autocatalytic caspase-3 driven by amplified hTERT promoter synergistically suppresses human ovarian carcinoma growth in vitro and in mice.Human Insulin-like Growth Human Interleukin-33 IL-3 Human Interleukin-32 alph Human Insulin-like Growth Human integrin aVb3, affi Th1 Th2 Th17 (Human) Anti Chemokine (Human) Antibod Cytokine (Human) Antibody Growth Factor (Human) Ant Th1 Th2 Th17 (Human) Anti Infiltrating duct carcino Human breast invasive duc
#23686785 2013/09/30 Save this To Up
Anticancer activity of tolfenamic acid in medulloblastoma: a preclinical study.Medulloblastoma (MB) is the most common malignancy in children arising in the brain. Morbidities associated with intensive therapy are serious concerns in treating MB. Our aim was to identify novel targets and agents with less toxicity for treating MB. Specificity protein 1 (Sp1) transcription factor regulates several genes involved in cell proliferation and cell survival including survivin, an inhibitor of apoptosis protein. We previously showed that tolfenamic acid (TA), a nonsteroidal anti-inflammatory drug, inhibits neuroblastoma cell growth by targeting Sp1. We investigated the anticancer activity of TA using human MB cell lines and a mouse xenograft model. DAOY and D283 cells were treated with vehicle (dimethyl sulfoxide) or TA (5-50 μg/ml), and cell viability was measured at 1-3 days posttreatment. TA inhibited MB cell growth in a time- and dose-dependent manner. MB cells were treated with vehicle or TA (10 μg/ml), and the effect on cell apoptosis was measured. Apoptosis was analyzed by flow cytometry (annexin V staining), and caspase 3/7 activity was determined using Caspase-Glo kit. The expression of Sp1, cleaved poly(ADP-ribose) polymerase (c-PARP), and survivin was determined by Western blot analysis. TA inhibited the expression of Sp1 and survivin and upregulated c-PARP. Athymic nude mice were subcutaneously injected with D283 cells and treated with TA (50 mg/kg, three times per week) for 4 weeks. TA caused a decrease of ~40 % in tumor weight and volume. The tumor growth inhibition was accompanied by a decrease in Sp1 and survivin expression in tumor tissue. These preclinical data demonstrate that TA acts as an anticancer agent in MB potentially targeting Sp1 and survivin.
2591 related Products with: Anticancer activity of tolfenamic acid in medulloblastoma: a preclinical study.MarkerGeneTM Live Dead As GST Inhibitor 2 (Ethacryn Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri Alkaline Phospatase (ALP) α-Acetamino-α-carboxy-( N-Acetyl-2-O-(5-bromo-1H- (1R,3S)-1-(1,3-Benzodioxo (1S,3S)-1-(1,3-Benzodioxo (1S,3S)-1-(1,3-Benzodioxo (1R,3S)-1-(1,3-Benzodioxo Rabbit Anti-IAA (Indole-3
#23546591 2013/05/31 Save this To Up
Preclinical evaluation of combined TKI-258 and RAD001 in hepatocellular carcinoma.RAD001 targets at the mammalian target of rapamycin (mTOR), while TKI-258 is a potent tyrosine kinase inhibitor targeting at fibroblast growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor and c-kit. We aim to study the activity of combined RAD001 and TKI-258 in cell lines and xenograft model of hepatocellular carcinoma (HCC), with reference to the parallel and upstream pathways of Akt-mTOR axis.
2472 related Products with: Preclinical evaluation of combined TKI-258 and RAD001 in hepatocellular carcinoma.TKI-258 Mechanisms: FGFR Liver hepatocellular carc Liver cancer (hepatocellu Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma Normal liver and hepatoce Multi organ carcinoma tis Multi organ carcinoma tis Pancreatic carcinoma and Carcinoma with adjacent t
#23427297 2013/05/10 Save this To Up
Tandutinib inhibits the Akt/mTOR signaling pathway to inhibit colon cancer growth.The c-Kit receptor can activate distinct signaling pathways including phosphoinositide 3-kinase (PI3K)/Akt and mTOR. Aberrant c-Kit activation protects cells from apoptosis and enhances invasion of colon carcinoma cells. Tandutinib is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases including c-Kit. We determined the effect of tandutinib on colon cancer growth and identified a mechanism of action. Tandutinib inhibited phosphorylation of c-Kit, Akt, mTOR, and p70S6 kinase. In addition, tandutinib significantly inhibited the proliferation and colony formation ability of colon cancer cell lines but did not affect normal colonic epithelial cells. There were increased levels of activated caspase-3 and Bax/Bcl2 ratio, coupled with a reduction in cyclin D1, suggesting apoptosis. There was also a downregulation of COX-2, VEGF, and interleukin-8 expression, suggesting effects on cancer-promoting genes. In addition, overexpressing constitutively active Akt partially suppressed tandutinib-mediated colon cancer cell growth. In vivo, intraperitoneal administration of tandutinib significantly suppressed growth of colon cancer tumor xenografts. There was a reduction in CD31-positive blood vessels, suggesting that there was an effect on angiogenesis. Tandutinib treatment also inhibited the expression of cancer-promoting genes COX-2 and VEGF and suppressed the activation of Akt/mTOR signaling proteins in the xenograft tissues. Together, these data suggest that tandutinib is a novel potent therapeutic agent that can target the Akt/mTOR/p70S6K signaling pathway to inhibit tumor growth and angiogenesis.
1348 related Products with: Tandutinib inhibits the Akt/mTOR signaling pathway to inhibit colon cancer growth.PathwayReady™ PI3 K Akt AKT PKB Signaling Phospho IGF-1R Signaling Phospho- PathwayReady™ MAP Kinas PathwayReady™ EGFR Sign PathwayReady™ JAK STAT DiscoveryPak™ Hedgehog Top 4 types of cancer (co Top 4 types of cancer (co Top 4 types of cancer (co Top 4 types of cancer (co Tissue microarray of top
#19383925 2009/05/01 Save this To Up
Kit inhibitor APcK110 induces apoptosis and inhibits proliferation of acute myeloid leukemia cells.Kit is a membrane-bound tyrosine kinase and receptor for stem cell factor (SCF) with a crucial role in hematopoiesis. Mutations of KIT occur in almost half of patients with core-binding factor leukemias, in which they have been associated with worse outcome. Development of new compounds targeting Kit may therefore hold promise for therapy. We investigated the activity and mechanism of action of APcK110, a novel Kit inhibitor, in the mastocytosis cell line HMC1.2 (KITV560G and KITD816V), acute myeloid leukemia (AML) lines OCIM2 and OCI/AML3 (both wild-type), and primary samples from patients with AML. We show that (a) APcK110 inhibits proliferation of the mastocytosis cell line HMC1.2 and the SCF-responsive cell line OCI/AML3 in a dose-dependent manner; (b) APcK110 is a more potent inhibitor of OCI/AML3 proliferation than the clinically used Kit inhibitors imatinib and dasatinib and at least as potent as cytarabine; (c) APcK110 inhibits the phosphorylation of Kit, Stat3, Stat5, and Akt in a dose-dependent fashion, showing activity of APcK110 on Kit and its downstream signaling pathways; (d) APcK110 induces apoptosis by cleavage of caspase-3 and poly(ADP-ribose) polymerase; and (e) APcK110 inhibits proliferation of primary AML blasts in a clonogenic assay but does not affect proliferation of normal colony-forming cells. Although APcK110 activity may partly depend on cytokine responsiveness (e.g., SCF) and not exclusively KIT mutation status, it remains a potent inhibitor of AML and mastocytosis cell lines and primary AML samples. APcK110 and similar compounds should be evaluated in clinical trials of patients with AML.
2978 related Products with: Kit inhibitor APcK110 induces apoptosis and inhibits proliferation of acute myeloid leukemia cells.Fontana-Masson Stain Kit Fontana-Masson Stain Kit Epidermal Growth Factor ( Epidermal Growth Factor ( Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Phosphatidy Cell Meter™ Caspase 3 7 Cell Meter™ Caspase 3 7 Cell Meter™ Caspase 3 7
#18398841 2008/04/30 Save this To Up
A celecoxib derivative inhibits focal adhesion signaling and induces caspase-8-dependent apoptosis in human acute myeloid leukemia cells.Most acute myeloid leukemias (AMLs), including those with c-Kit or FLT3 mutations, show enhanced anchorage independent growth associated with constitutive activation of focal adhesion proteins. Moreover, these alterations increase cell survival, inhibit apoptosis and are associated with poor prognosis and resistance to chemotherapy. Therefore, the induction of apoptosis by selective inhibition of focal adhesion signaling may represent a novel anti-AML therapy. Here, we have evaluated the antitumor effect and the mechanism of action of celecoxib and E7123, a non-Cox-2 inhibitor derivative, in a panel of human AML cell lines and bone marrow mononuclear cells from AML patients. Both compounds induce cell death by inhibiting focal adhesion signaling through p130Cas, FAK and c-Src, leading to caspase-8 dependent apoptosis. This mechanism of action differs from that of classical cytotoxic drugs or of other targeted therapies, and is amenable to rational drug development. Therefore, both drugs could be developed as AML therapeutics; nevertheless, E7123 shows more activity than celecoxib against AML cells, and may not present its Cox-2 dependent cardiovascular toxicity. Finally, our results support the evaluation of celecoxib in AML patients, and the preclinical evaluation of E7123, before its possible clinical testing.
2552 related Products with: A celecoxib derivative inhibits focal adhesion signaling and induces caspase-8-dependent apoptosis in human acute myeloid leukemia cells.Apoptosis (Human) Antibod Apoptosis (Human) Antibod Human Internal Mammary Ar GFP Expressing Human Inte Human intercellular adhes Rabbit Anti-Human Apoptos Anti C Reactive Protein A Anti AGO2 Human, Monoclon Anti AGO2 Human, Monoclon anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl
#14653950 2003/12/05 Save this To Up
Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line.To investigate the ability of an antisense RNA eukaryotic expression plasmid pcDNA3.1/survivin in down-regulating the expression level of survivin mRNA and survivin protein and reversed multidrug resistance (MDR) in adriamycin-resistant HL-60/ADR cell line.
2841 related Products with: Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line.DNA (cytosine 5) methyltr GLP 2 ELISA Kit, Rat Prog Cell cycle antibody array Cell Cycle Control Phosph pCAMBIA0105.1R Vector, (G pCAMBIA0305.1 Vector, (Gu pCAMBIA0305.2 Vector (Sec pCAMBIA0380 Vector (No Re pCAMBIA1105.1 (GusPlus™ pCAMBIA1105.1R Vecotr (Gu pCAMBIA1301 Vector (gusA pCAMBIA1302 Vector (mgfp5
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45 Fax 0032 16 50 90 45
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50 Fax 01 43 25 01 60
52062 Aachen Deutschland
Tel 0241 40 08 90 86 Fax 0241 55 91 05 36
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
Schweiz Züri +41435006251
Česká republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Ελλάς Αθήνα +302111768494
Magyarország Budapest +3619980547
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
GENTAUR Nederland BV
5521 DG Eersel Nederland
Tel 0208-080893 Fax 0497-517897
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93 Fax 02 36 00 65 94
53 Iskar Str. 1191 Kokalyane, Sofia