Obatoclax Mesylate (GX15-070)

For research use only.

Catalog No.S1057

103 publications

Obatoclax Mesylate (GX15-070) Chemical Structure

CAS No. 803712-79-0

Obatoclax Mesylate (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 3.

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Selleck's Obatoclax Mesylate (GX15-070) has been cited by 103 publications

Purity & Quality Control

Choose Selective Bcl-2 Inhibitors

Biological Activity

Description Obatoclax Mesylate (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 3.
Features Potential 1st-in-class small molecule antagonist of Bcl-2 designed to inhibit all relevant Bcl-2 family members, including Mcl-1.
Targets
Bcl-2 [1]
(Cell-free assay)
0.22 μM(Ki)
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Cyclin D1 / p27 Kip1 ; 

PubMed: 28382170     


Western blotting showed that Obatoclax impacted cell cycle distribution through lowering cyclin D1 in K1 cells but in BCPAP cells, it impacted expression of p27 Kip1 rather than cyclin D1.

p-Cyclin D1 ; 

PubMed: 28035994     


Cell line-dependent effect of obatoclax on cyclin D1 T286 phosphorylation. HCT116, HT-29, and LoVo cells were subject to 24 h-treatment with obatoclax (200 nM), followed by immunoblotting to evaluate the levels of threonine 286 (T286)-phosphorylated cyclin D1 (p-Cyclin D1) at indicated time points. α-Tubulin levels served as equal loading control;

p-GSK3β / GSK3β / p-ERK / ERK / p-p38 / p38; 

PubMed: 28035994     


Obatoclax inhibits GSK3β but activates p38 (MAPK), while barely affecting ERK1/2 activity in HT-29 cells. HT-29 cells were exposed to 200 nM of obatoclax for 24 h. The status of activation of GSK3β, ERK1/2, and p38(MAPK) at indicated time points was determined by immunoblotting for corresponding phosphorylation. Specifically, serine 9-phosphorylation of GSK3β (p-GSK3β) reveals inhibition of GSK3β activity, whereas dual phosphorylation at threonine 202/tyrosine 204 of ERK1/2 (p-ERK1/2) and threonine 180/tyrosine 182 of p38 MAPK (p-p38) indicate activation of ERK1/2 and p38(MAPK), respectively. α-Tubulin levels served as equal loading control;

28382170 28035994
Growth inhibition assay
Cell proliferation ; 

PubMed: 28035994     


Obatoclax inhibits colorectal cancer cell proliferation. Human colorectal carcinoma cell lines HCT116, HT-29, and LoVo cells were treated with obatoclax (0, 50, 100, 200 nM) for 24, 48, and 72 h. The numbers of cells at each time point were counted using a Neubauer chamber. Data were presented as the percentage relative to the drug-untreated control.

Cell viability; 

PubMed: 21368880     


H727 NSCLC cells are resistant to obatoclax. H727 and H1975 NSCLC cells were treated with obatoclax at the indicated doses for 48 (left) or 72 h (right), and the viability of cells determined by ViaLight assay. The EC50 values of cells at 48 h were; H1975 267 nM; H727 3.2 μM. The EC50 values of cells at 72 h were; H1975 66 nM; H727 621 nM. Data are expressed as mean±S.D. 

28035994 21368880
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]

Protocol

Kinase Assay:[1]
- Collapse

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 Research:[2]
- Collapse
  • 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.
    (Only for Reference)
Animal Research:[1]
- Collapse
  • 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
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 83 mg/mL (200.73 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* 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 Information

Molecular Weight 413.49
Formula

C20H19N3O.CH4O3S

CAS No. 803712-79-0
Storage powder
in solvent
Synonyms N/A
Smiles CC1=CC(=C(N1)C=C2C(=CC(=C3C=C4C=CC=CC4=N3)N2)OC)C.CS(=O)(=O)O

In vivo Formulation Calculator (Clear solution)

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    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00438178 Completed Drug: Obatoclax mesylate (GX15-070MS) Hematological Malignancies Gemin X|Teva Pharmaceutical Industries October 2005 Phase 1
NCT00600964 Completed Drug: GX15-070MS Chronic Lymphocytic Leukemia Gemin X|Teva Pharmaceutical Industries September 2004 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Bcl-2 Signaling Pathway Map

Bcl-2 Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID