Antibodies
Obatoclax Mesylate (GX15-070)
- 貨號 Cat. No.
- S1057
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
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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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
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. | |||||
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| 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. |
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Cell Assay: [2]
| Cell lines | Human MM cells (HMCLs), peripheral blood lymphocytes (PBLs), bone marrow stromal cells (BMSCs) |
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| 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. |
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| 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 |
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 |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 83 mg/mL (200 mM) |
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| 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 |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.41349 | 4.1349 | 8.2698 | 12.4047 |
Customer Reviews (5)
 Click to enlarge | 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. |
Product Citations (12)
Met-independent lung cancer cells evading EGFR kinase inhibitors are therapeutically susceptible to BH3 mimetic agents. [Fan W, et al. Cancer Res 2011;71(13):4494-505]
MET-independent lung cancer cells evading EGFR kinase inhibitors are therapeutically susceptible to BH3 mimetic agents [Fan W Cancer Res 2011;10.1158/0008-5472.CAN-10-2668]
Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1. [Ying S, et al. Cancer Res 2012;72(11):2814-21]
