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TW-37 Bcl-2 Inibitore

N. Cat.: S1121

TW-37 è un nuovo inibitore non peptidico della Bcl-2, Bcl-xL e Mcl-1 ricombinante con Ki di 0,29 μM, 1,11 μM e 0,26 μM in saggi senza cellule, rispettivamente.
TW-37 Bcl-2 Inibitore Chemical Structure

Struttura chimica

Peso molecolare: 573.7

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.78%
99.78

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari Tipo di saggio Concentrazione Tempo di incubazione Formulazione Descrizione dell'attività PMID
human JAR cell Growth inhibition assay Inhibition of human JAR cell growth in a cell viability assay, IC50=2.6 nM
human Ca9-22 cell Growth inhibition assay Inhibition of human Ca9-22 cell growth in a cell viability assay, IC50=3.82 nM
human CHL-1 cell Growth inhibition assay Inhibition of human CHL-1 cell growth in a cell viability assay, IC50=11.9 nM
human A549 cell Growth inhibition assay Inhibition of human A549 cell growth in a cell viability assay, IC50=14.09 nM
human RKO cell Growth inhibition assay Inhibition of human RKO cell growth in a cell viability assay, IC50=15.17 nM
human GCIY cell Growth inhibition assay Inhibition of human GCIY cell growth in a cell viability assay, IC50=20.83 nM
human BHT-101 cell Growth inhibition assay Inhibition of human BHT-101 cell growth in a cell viability assay, IC50=21.83 nM
human Hs-578-T cell Growth inhibition assay Inhibition of human Hs-578-T cell growth in a cell viability assay, IC50=23.59 nM
human SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=28.68 nM
human NB7 cell Growth inhibition assay Inhibition of human NB7 cell growth in a cell viability assay, IC50=29.28 nM
human YKG-1 cell Growth inhibition assay Inhibition of human YKG-1 cell growth in a cell viability assay, IC50=29.76 nM
human HuH-7 cell Growth inhibition assay Inhibition of human HuH-7 cell growth in a cell viability assay, IC50=32.82 nM
human SAS cell Growth inhibition assay Inhibition of human SAS cell growth in a cell viability assay, IC50=33.18 nM
human UACC-62 cell Growth inhibition assay Inhibition of human UACC-62 cell growth in a cell viability assay, IC50=34.35 nM
human AGS cell Growth inhibition assay Inhibition of human AGS cell growth in a cell viability assay, IC50=37.53 nM
human SK-MEL-30 cell Growth inhibition assay Inhibition of human SK-MEL-30 cell growth in a cell viability assay, IC50=37.97 nM
human A427 cell Growth inhibition assay Inhibition of human A427 cell growth in a cell viability assay, IC50=44.69 nM
human DU-145 cell Growth inhibition assay Inhibition of human DU-145 cell growth in a cell viability assay, IC50=52.13 nM
human HCT-116 cell Growth inhibition assay Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=52.66 nM
human A673 cell Growth inhibition assay Inhibition of human A673 cell growth in a cell viability assay, IC50=53.85 nM
human SF126 cell Growth inhibition assay Inhibition of human SF126 cell growth in a cell viability assay, IC50=57.07 nM
human SW872 cell Growth inhibition assay Inhibition of human SW872 cell growth in a cell viability assay, IC50=58.9 nM
human NCI-H1581 cell Growth inhibition assay Inhibition of human NCI-H1581 cell growth in a cell viability assay, IC50=67.64 nM
human SK-MEL-5 cell Growth inhibition assay Inhibition of human SK-MEL-5 cell growth in a cell viability assay, IC50=69.25 nM
human CP50-MEL-B cell Growth inhibition assay Inhibition of human CP50-MEL-B cell growth in a cell viability assay, IC50=69.59 nM
human YH-13 cell Growth inhibition assay Inhibition of human YH-13 cell growth in a cell viability assay, IC50=70.59 nM
human LXF-289 cell Growth inhibition assay Inhibition of human LXF-289 cell growth in a cell viability assay, IC50=72.85 nM
human MC-IXC cell Growth inhibition assay Inhibition of human MC-IXC cell growth in a cell viability assay, IC50=75.33 nM
human NB14 cell Growth inhibition assay Inhibition of human NB14 cell growth in a cell viability assay, IC50=76.45 nM
human HEC-1 cell Growth inhibition assay Inhibition of human HEC-1 cell growth in a cell viability assay, IC50=81.37 nM
human U-87-MG cell Growth inhibition assay Inhibition of human U-87-MG cell growth in a cell viability assay, IC50=82.24 nM
human HOS cell Growth inhibition assay Inhibition of human HOS cell growth in a cell viability assay, IC50=84.71 nM
human HUTU-80 cell Growth inhibition assay Inhibition of human HUTU-80 cell growth in a cell viability assay, IC50=87.01 nM
human A375 cell Growth inhibition assay Inhibition of human A375 cell growth in a cell viability assay, IC50=88.83 nM
human A204 cell Growth inhibition assay Inhibition of human A204 cell growth in a cell viability assay, IC50=97.84 nM
human GB-1 cell Growth inhibition assay Inhibition of human GB-1 cell growth in a cell viability assay, IC50=98.69 nM
human MDA-MB-231 cell Growth inhibition assay Inhibition of human MDA-MB-231 cell growth in a cell viability assay, IC50=0.10807 μM
human SW982 cell Growth inhibition assay Inhibition of human SW982 cell growth in a cell viability assay, IC50=0.1107 μM
human SW756 cell Growth inhibition assay Inhibition of human SW756 cell growth in a cell viability assay, IC50=0.11236 μM
human MG-63 cell Growth inhibition assay Inhibition of human MG-63 cell growth in a cell viability assay, IC50=0.11248 μM
human Daoy cell Growth inhibition assay Inhibition of human Daoy cell growth in a cell viability assay, IC50=0.14073 μM
human MDA-MB-453 cell Growth inhibition assay Inhibition of human MDA-MB-453 cell growth in a cell viability assay, IC50=0.15188 μM
human HT-144 cell Growth inhibition assay Inhibition of human HT-144 cell growth in a cell viability assay, IC50=0.15201 μM
human LoVo cell Growth inhibition assay Inhibition of human LoVo cell growth in a cell viability assay, IC50=0.16093 μM
human NY cell Growth inhibition assay Inhibition of human NY cell growth in a cell viability assay, IC50=0.17762 μM
human SW1783 cell Growth inhibition assay Inhibition of human SW1783 cell growth in a cell viability assay, IC50=0.21301 μM
human A2780 cell Growth inhibition assay Inhibition of human A2780 cell growth in a cell viability assay, IC50=0.21846 μM
human MDA-MB-361 cell Growth inhibition assay Inhibition of human MDA-MB-361 cell growth in a cell viability assay, IC50=0.2264 μM
human RPMI-2650 cell Growth inhibition assay Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=0.23831 μM
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare 573.7 Formula

C33H35NO6S

 Conservazione (Dalla data di ricezione)
N. CAS 877877-35-5 Scarica SDF Conservazione delle soluzioni stock

Sinonimi N/A Smiles CC(C)C1=CC=CC=C1CC2=CC(=C(C(=C2O)O)O)C(=O)NC3=CC=C(C=C3)S(=O)(=O)C4=CC=CC=C4C(C)(C)C

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 115 mg/mL (200.45 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 4 mg/mL

Water : Insoluble

Calcolatore di Molarità

Massa Concentrazione Volume Peso molecolare
Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo
Lotto:

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

mg/kg g μL

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC50/Ki
Mcl-1
(Cell-free assay)
0.26 μM(Ki)
Bcl-2
(Cell-free assay)
0.29 μM(Ki)
Bcl-xL
(Cell-free assay)
1.11 μM(Ki)
In vitro

TW-37 targets the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins bind, and shows higher affinity and selectivity for Bcl-2 and Mcl-1 over Bcl-xL with Ki values of 0.29 μM, 0.26 μM and 1.11 μM, respectively. In vitro, this compound shows significant anti-proliferative and pro-apoptotic effect in a de novo chemo-resistant WSU-DLCL2 lymphoma cell line and primary cells obtained from a lymphoma patient without effects on normal peripheral blood lymphocytes. It exhibits the inhibitory effect on both cell growth and cell death in endothelial cell with IC50 of approximately 1.8 μM without effect on the fibroblasts exposed to the same concentration range as the endothelial cells. In addition, this chemical also shows the anti-proliferation effects in MCF-7, LNCaP, and SLK tumor cell lines with the same or lower concentration range than those required to inhibit endothelial cell growth.

Saggio chinasico
Saggio di legame basato sulla polarizzazione della fluorescenza per le proteine ricombinanti Bcl-2, Bcl-XL e Mcl-1
Per questo saggio, vengono impiegati il peptide BH3 di 21 residui QEDIIRNIARHLAQVGDSMDR derivato da Bid marcato con FAM-Bid e le proteine ricombinanti derivate da Bcl-2 umana, Bcl-X L e Mcl-1. Si determina che FAM-Bid ha una Ki di 11 nM per la proteina Bcl-2, 25 nM per la proteina Bcl-XL e 5,7 nM per la proteina Mcl-1. Il saggio di legame competitivo per Bcl-XL è lo stesso di quello per Bcl-2 con le seguenti eccezioni: 30 nM di proteina Bcl-XL e 2,5 nM di peptide FAM-Bid nel seguente tampone di saggio [50 mM Tris-Bis (pH 7.4) e 0,01% di gamma-globulina bovina].
In vivo

TW-37 shows a maximum tolerated dose (MTD) of 40 mg/kg for three i.v. injections in severe combined immunodeficient (SCID) mice when given alone, and enhances tumor inhibitory effect of the CHOP regimen. This compound, administrated by i.v. produces the antiangiogenic effect by decreasing the density of functional human microvessels in the severe combined immunodeficient mouse model of human angiogenesis. The combination of this chemical and MEK inhibitors synergistically block melanoma cell growth in mice by a significant reduction in tumor volume and tumor mass.

Riferimenti