ArtNr |
S1057-5 |
Hersteller |
Selleckchem
|
CAS-Nr. |
803712-79-0 |
Menge |
5 mg |
Kategorie |
|
Typ |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
Bcl-2;Bcl-2 |
Similar products |
Obatoclax |
Lieferbar |
|
Administration |
Administered intravenously (tail vein) once a day |
Animal Models |
Female BALB/c or CB17 SCID/SCID mice bearing SW480, C33A, PC3, and 4T1 cells are used. |
Cell lines |
Human MM cells (HMCLs), peripheral blood lymphocytes (PBLs), bone marrow stromal cells (BMSCs) |
Chemical Name |
(Z)-2-(5-((3, 5-dimethyl-1H-pyrrol-2-yl)methylene)-4-methoxy-5H-pyrrol-2-yl)-1H-indole mesylate |
Clinical Trials |
Obatoclax, combined with rituximab and bendamustine, is currently under Phase I/II clinical trials in relapsed or refractory indolent non-hodgkin's lymphoma. |
Concentrations |
ca.10 uM |
Description |
Obatoclax (GX15-070) is an inhibitor of Bcl-2 with Ki of 0.22 uM. |
Dosages |
0.0313, 0.25, 0.5 and 2 mg/kg |
Features |
Obatoclax is a potential first-in-class small molecule antagonist of Bcl-2 designed to inhibit all relevant members of the Bcl-2 family of proteins, including the dominant member, Mcl-1. |
Formulation |
Obatoclax (tartrate salt) is formulated in 9.6% polyethylene glycol 300, 0.4% polysorbate 20, and 5% dextrose, while for the 4T1 tumor model, Obatoclax is formulated at a concentration of 0.6 mg/mL in 9.48% polyethylene glycol, 0.38% polysorbate 20, 1.2 mg/mL mannitol, and 5% dextrose. |
IC50 |
0.22 uM (Ki) [1], 0.22 uM (Ki) [1], 0.22 uM (Ki) [1], 0.22 uM (Ki) [1], 0.22 uM (Ki) [1], 0.22 uM (Ki) [1] |
In vitro |
Obatoclax completely inhibits Bak recovery of Mcl-1 at 5 uM in SK-Mel5 cells and overcomes resistance to ABT-373-induced apoptosis conferred by Mcl-1 in KB/Bcl-2 cells. [1] Obatoclax is a BH3 mimetic which binds to a broad spectrum of Bcl-2 family members, including Bcl-2, Bcl-xL, and Mcl-1. Obatoclax uniquely displaces BH3 domains by activation of the pocket of Mcl-1 followed by a triggering of apoptosis mediated by oligomerization of Bak and release of cytochrome c. Obatoclax is sensitive to Bcl-xL in cell lines lacking it or showing low expression. It shows low cytotoxicity to Mcl-1, Bcl-2, and Bcl-xL in all the strongly-expressed cell lines. Obatoclax inhibits multiple myeloma (MM) cell lines (KMS12PE, KMS18, MY5, etc.) with IC50 values ranging from 52 to 1100 nM and the inhibition is umimpaired even in the presence of IL-6 or IGF-1, which are resistance to cytotoxic agents, at a concentration of 150 nM. Obatoclax enhances the antimyeloma activity induced by melphalan, dexamethasone, or bortezomib. [2] Obatoclax potentiates TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-mediated apoptosis by unsequestering Bak and Bim from Bcl-2/Bcl-xL or Mcl-1 proteins in PANC-1 and BxPC-3 cells. [3] |
In vivo |
Obatoclax also exhibits high antitumor activity in SCID mice bearing human C33A cerivical carcinoma tumors at a dose of 0.5 mg/kg. [1] |
Incubation Time |
48-72 hours |
Kinase Assay |
Bcl-2 Binding affinity calculation, A predicted binding affinity for Obatoclax binding to BCL-2 is calculated using the SIE scoring function. [4] As a control in determining the reliability of the calculation, predicted binding affinities Ki) are calculated for a set of 12 small molecules with experimentally measured binding affinities to BCL-2. |
Method |
Obatoclax is dissolved in DMSO at a stock concentration of 5 mM. Cell viability is assayed by MTT. Human MM cells (HMCLs), peripheral blood lymphocytes (PBLs), bone marrow stromal cells (BMSCs) are seeded in 96-well plates at a density of 2, 104 per well for HMCLs or 5ca.10, 103 for PBLs. Various concentrations of Obatoclax are added to the cells, with or without IGF-1 (50 ng/mL) or IL-6 (10 ng/mL). Cells are incubated for 48-72 hours and cell viability is determined. |
Molecular Weight (MW) |
413, 49 |
Picture ChemicalStructure Description |
Obatoclax mesylate (GX15-070) Chemical Structure |
Picture Description 1 |
, , Dr Christine Hawkins of La Trobe University, Obatoclax mesylate (GX15-070)purchased from Selleck, MEF cells were treated for 24 hours with the Bcl-2 antagonists Obatoclax Mesylate at the indicated doses.Acute survival was monitored by replacing the drug-containing media with normal media and incubating the cells until visible colonies formed.Clonogenic survival is expressed relative to the numbers of colonies formed following 24 hours incubation in normal media(lacking drugs). |
Picture Description 2 |
, , Dr. Zhang, of Tianjin Medical University, Obatoclax mesylate (GX15-070)purchased from Selleck, MDB-MA-231 cells were exposed to 30 M cisplatin in the absence or in thepresence of 1 M Obatoclax Mesylate .The cell were stained with Hoechst 33342, MitoTracker Red and Yo-pro-1. |
Solubility (25C) |
DMSO 83 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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