Obatoclax Mesylate (GX15-070)

Catalog No.S1057

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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Obatoclax Mesylate (GX15-070) Chemical Structure

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

Validation & Quality Control

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Quality Control & MSDS

Related Compound Libraries

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

Bcl-2 Inhibitors with Unique Features

  • Pan Bcl-2 Inhibitor

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

  • 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

    BAM7 Direct and selective activator of proapoptotic Bax with EC50 of 3.3 μM.

  • 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

  • Compare Bcl-2 Inhibitors
    Compare Bcl-2 Products
  • Research Area

Product Description

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.
Targets Bcl-2 [1]
(Cell-free assay)
IC50 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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IST-SL1NUPWZ3VwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MonMTWM2OD14LkWzPVQ5KM7:TR?=MlXEV2FPT0WU
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NCI-H1155NWjGZlZQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MU\JR|UxRTZwOUW1PFEh|ryPNWWwO3h1W0GQR1XS
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SW948MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXjJd3ZbUUN3ME23MlU5Ozl3IN88US=>Mn\yV2FPT0WU
NCI-H524Mk\JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1G0S2lEPTB;OT61PFYzQCEQvF2=M4HHRXNCVkeHUh?=
KOSC-2M1XEWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MoHRTWM2OD17Lk[yPFM1KM7:TR?=M2nHV3NCVkeHUh?=
T-24NWG1VmptT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHnhZ|ZKSzVyPUmuPVQ1OTVizszNMn65V2FPT0WU
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UACC-812MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M2WxfmlEPTB;MUGuO|E4KM7:TR?=M33KSXNCVkeHUh?=
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NCI-H1395NUjKVnNOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M1nF[2lEPTB;M{KuNlQ{OSEQvF2=MofyV2FPT0WU
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COR-L88NH;oRWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIjrfplKSzVyPUS0MlA3PjVizszNM37XfHNCVkeHUh?=
NCI-H889M2\GN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXTJR|UxRTR3LkCwPFch|ryPNXXieWZ{W0GQR1XS
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KARPAS-299MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVT0UZhDUUN3ME20O{4yQTl|IN88US=>MV7TRW5ITVJ?

... Click to View More Cell Line Experimental Data

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.
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 m
Dosages 0.0313, 0.25, 0.5 and 2 mg/kg
Administration Administered intravenously (tail vein) once a day

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Nguyen M, et al. Proc Natl Acad Sci, 2007, 104(49), 19512-191517.

[2] Trudel S, et al. Blood, 2009, 113(2), 299-305.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01563601 Withdrawn Extensive-stage Small Cell Lung Cancer Cephalon|Teva Pharmaceutical Industries August 2012 Phase 3
NCT01238146 Withdrawn Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue|Nodal Marginal Zone B-cell Lymphoma|Recurrent Grade 1 Follicular Lymp  ...more 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|Recurrent Mantle Cell Lymphoma|Recurrent Marginal Zone Lymphoma|Splenic Marginal Zone Lymphoma National Cancer Institute (NCI) October 2010 Phase 1|Phase 2
NCT00933985 Terminated Acute Leukemias of Ambiguous Lineage|Acute Undifferentiated Leukemia|Angioimmunoblastic T-cell Lymphoma|Blastic Phase Chronic Myelogenous Leukemia|  ...more Acute Leukemias of Ambiguous Lineage|Acute Undifferentiated Leukemia|Angioimmunoblastic T-cell Lymphoma|Blastic Phase Chronic Myelogenous Leukemia|Childhood Burkitt Lymphoma|Childhood Chronic Myelogenous Leukemia|Childhood Diffuse Large Cell Lymphoma|Childhood Immunoblastic Large Cell Lymphoma|Childhood Nasal Type Extranodal NK/T-cell Lymphoma|Cutaneous B-cell Non-Hodgkin Lymphoma|Hepatosplenic T-cell Lymphoma|Intraocular Lymphoma|Noncutaneous Extranodal Lymphoma|Peripheral T-cell Lymphoma|Recurrent Childhood Acute Lymphoblastic Leukemia|Recurrent Childhood Acute Myeloid Leukemia|Recurrent Childhood Anaplastic Large Cell Lymphoma|Recurrent Childhood Grade III Lymphomatoid Granulomatosis|Recurrent Childhood Large Cell Lymphoma|Recurrent Childhood Lymphoblastic Lymphoma|Recurrent Childhood Small Noncleaved Cell Lymphoma|Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma|Recurrent Mycosis Fungoides/Sezary Syndrome|Recurrent/Refractory Childhood Hodgkin Lymphoma|Refractory Chronic Lymphocytic Leukemia|Refractory Hairy Cell Leukemia|Relapsing Chronic Myelogenous Leukemia|Small Intestine Lymphoma|Unspecified Childhood Solid Tumor, Protocol Specific National Cancer Institute (NCI) June 2009 Phase 1
NCT00918931 Terminated Leukemia|Systemic Mastocytosis M.D. Anderson Cancer Center|Gemin X June 2009 Phase 2
NCT00719901 Terminated Refractory Multiple Myeloma|Stage I Multiple Myeloma|Stage II Multiple Myeloma|Stage III Multiple Myeloma National Cancer Institute (NCI) July 2008 Phase 1|Phase 2

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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 solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 83 mg/mL (200.73 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

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.

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

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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