Obatoclax Mesylate (GX15-070)

Obatoclax (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 1/2.

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Obatoclax Mesylate (GX15-070) Chemical Structure

Obatoclax Mesylate (GX15-070) Chemical Structure
Molecular Weight: 413.49

Validation & Quality Control

Customer Reviews(5)

Quality Control & MSDS

Related Compound Libraries

Obatoclax Mesylate (GX15-070) is available in the following compound libraries:

Bcl-2 Inhibitors with Unique Features

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  • Most Potent Bcl-2 Inhibitor

    ABT-263 (Navitoclax) Bcl-xL, Ki≤ 0.5 nM; Bcl-2, Ki≤ 1 nM; Bcl-w, Ki≤ 1 nM.

  • Newest Bcl-2 Family Activator

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  • Classic Bcl-2 Inhibitor

    ABT-737 BH3-mimetic inhibitor, Bcl-xL, EC50=78.7 nM; Bcl-2, EC50=30.3 nM; Bcl-w, EC50=197.8 nM.

Product Information

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  • Research Area

Product Description

Biological Activity

Description Obatoclax (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 1/2.
Targets Bcl-2
IC50 0.22 μM (Ki) [1]
In vitro Obatoclax completely inhibits Bak recovery of Mcl-1 at 5 μM 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]
Features Potential 1st-in-class small molecule antagonist of Bcl-2 designed to inhibit all relevant Bcl-2 family members, including Mcl-1.

Protocol(Only for Reference)

Kinase Assay: [1]

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.

Cell Assay: [2]

Cell lines Human MM cells (HMCLs), peripheral blood lymphocytes (PBLs), bone marrow stromal cells (BMSCs)
Concentrations ~10 μM
Incubation Time 48-72 hours
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 5~10 × 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.

Animal Study: [1]

Animal Models Female BALB/c or CB17 SCID/SCID mice bearing SW480, C33A, PC3, and 4T1 cells are used.
Dosages 0.0313, 0.25, 0.5 and 2 mg/kg
Administration Administered intravenously (tail vein) once a day
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
1

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT00918931 Terminated Leukemia|Systemic Mastocytosis M.D. Anderson Cancer Center|Gemin X 2009-06 Phase 2
NCT00933985 Active, not recruiting Acute Undifferentiated Leukemia|Blastic Phase Chronic Myelogenous Leukemia|Childhood Burkitt Lymphoma|Childhood Chronic Myelogenous Leukemia|Cutaneous B-cell Non-Hodgkin Lymphoma etc. National Cancer Institute (NCI) 2009-06 Phase 1
NCT01150656 Active, not recruiting Leukemia National Cancer Institute (NCI)|Children's Oncology Group 2010-06
NCT01238146 Withdrawn Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue|Nodal Marginal Zone B-cell Lymphoma|Recurrent Grade 1 Follicular Lymphoma|Recurrent Grade 2 Follicular Lymphoma etc. National Cancer Institute (NCI) 2010-10 Phase 1|Phase 2
NCT01563601 Withdrawn Extensive-stage Small Cell Lung Cancer Teva Pharmaceutical Industries|Cephalon 2012-08 Phase 3

Chemical Information

Download Obatoclax Mesylate (GX15-070) SDF
Molecular Weight (MW) 413.49
Formula

C20H19N3O.CH4O3S

CAS No. 803712-79-0
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Syonnyms N/A
Solubility (25°C) * In vitro DMSO 83 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (Z)-2-(5-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-4-methoxy-5H-pyrrol-2-yl)-1H-indole mesylate

Preparing Stock Solutions

Stock Solution (1ml DMSO) 1mM 10mM 20mM 30mM
Mass(mg) 0.41349 4.1349 8.2698 12.4047

Research Area

Customer Reviews (5)


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Rating
Source Cell Death and Disease (2012) 3, e299. Obatoclax Mesylate (GX15-070) purchased from Selleck
Method Viability assay
Cell Lines BM3.3 CD8 T cells
Concentrations 0.1-10uM
Incubation Time
Results T-cell activation induced resistance to Bcl-2 inhibition by ABT-737 (no binding of A1 and Mcl-1) and by Antimycin A (no binding of A1 only), but had no impact on the proapoptotic potency of the pan-Bcl-2 inhibitor obatoclax.

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Rating
Source Obatoclax Mesylate (GX15-070) purchased from Selleck
Method Cell Viability/Western Blot
Cell Lines Nalm-6 ABT-R cells
Concentrations 5-10 uM
Incubation Time 18 h
Results Nalm-6 ABT-R cells were sensitive to obatoclax; however, Nalm-6 cells were equally sensitive (IC50: 10 umol/L). Reh parental cells (IC50: 5umol/L) were also more sensitive to obatoclax compared with ABT-R cells, as measured by trypan blue exclusion. Mcl-1 protein levels were downregulated following obatoclax treatment. NOXA levels also increased, however these changes did not correlate with cell death.

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Rating
Source Dr Christine Hawkins of La Trobe University. Obatoclax Mesylate (GX15-070) purchased from Selleck
Method Clonogenic survival assay
Cell Lines MEF cells
Concentrations 0-300 ng/mL
Incubation Time 24 h
Results

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Rating
Source Dr. Zhang of Tianjin Medical University. Obatoclax Mesylate (GX15-070) purchased from Selleck
Method Hoechst staining
Cell Lines MDB-MA-231 cells
Concentrations 1 μM
Incubation Time
Results

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Rating
Source BMC Cancer 2011 11, 24. Obatoclax Mesylate (GX15-070) purchased from Selleck
Method Cell proliferation assays
Cell Lines SET-2 cells
Concentrations 1-10000 nM
Incubation Time 72 h
Results Incubation of SET-2 cells with sub-optimal concentrations of the pan-Bcl-2 family protein inhibitor obatoclax in cell proliferation assays lowered the GI 50 of NVP-BSK805 by 3 to 4 fold.

Product Citations (12)

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    Obatoclax (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 1/2.

    Features:Potential 1st-in-class small molecule antagonist of Bcl-2 designed to inhibit all relevant Bcl-2 family members, including Mcl-1.

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