Obatoclax mesylate (GX15-070)

Information	Obatoclax (GX15-070) is an inhibitor of Bcl-2 with K_i of 0.22 μM.
Targets	Bcl-2
IC50	0.22 μM (K_i) ^[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]
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.
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.

Information

Obatoclax (GX15-070) is an inhibitor of Bcl-2 with K_i of 0.22 μM.

Targets

Bcl-2

IC50

0.22 μM (K_i) ^[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]

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.

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.

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 K_i) are calculated for a set of 12 small molecules with experimentally measured binding affinities to BCL-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.

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 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 mg/mL mannitol, and 5% dextrose.
Dosages:	0.0313, 0.25, 0.5 and 2 mg/kg
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.

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.

Dosages:

0.0313, 0.25, 0.5 and 2 mg/kg

Administration:

Administered intravenously (tail vein) once a day

Molecular Weight (WM):	413.49
Formula:	C₂₀H₁₉N₃O.CH₄O₃S
CAS No.:	803712-79-0
Synonyms:	N/A

Molecular Weight (WM):

413.49

Formula:

C₂₀H₁₉N₃O.CH₄O₃S

CAS No.:

803712-79-0

Synonyms:

N/A

Dissolve in (25°C):	DMSO ≥83mg/mL
	Water <1mg/mL
	Ethanol <1mg/mL
Storage:	2 years-20°CPowder
	1 week-4°Cin DMSO
	1 month-80°in DMSO

You can order by phone, email or fax

Free Overnight Delivery on all orders over $ 500.

Recommended Products

Biological Activity

Protocol (Only for Reference)

Kinase Assay: [1]

Cell Assay: [2]

Animal Study:[1]

References

Chemical Information

Quality Control & MSDS

Research Area

Related Inhibitors

Secondary Antibodies

Loading Control Antibodies

Recommended Screening Libraries

Selleck's high quality products have been used in several published research findings, including the following:

We have 4 customer reviews of Obatoclax mesylate (GX15-070).

Average Customer Review

Our scientific support team are available to answer any questions or queries. Fill out an inquiry form for Obatoclax mesylate (GX15-070) for help.

Quality Matters

This product has been referenced in

Check our customer reviews

Kinase Assay: ^[1]

Cell Assay: ^[2]

Animal Study:^[1]

Our scientific support team are available to answer any questions or queries.
Fill out an inquiry form for Obatoclax mesylate (GX15-070) for help.