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Obatoclax Mesylate (also known as GX15 070), the mesylate salt of obatoclax, is a potent inhibitor of Bcl-2 (B-cell leukemia protein-2) protein with a Ki of 0.22 μM in a cell-free assay. Obatoclax interacts with BCL-2 and other members of the BCL-2 family that share the BH3-binding site, such as BCL-XL, MCL-1, A1, and BCL-B. Obatoclax mesylate, a pan-BCL-2 inhibitor, exhibits antitumor activity in mouse xenografts of solid tumor and myeloma cell lines and is being studied for the treatment of refractory malignancies. It directly induces apoptosis in cultured acute myeloid leukemia (AML) cells as well as primary patient samples. In many cancers, including those of the lymphatic system, breast, lung, prostate, and colon, the Bcl-2 protein family is overexpressed. Obatoclax is a Bcl-2 inhibitor, and as such, it has anticancer properties.
Physicochemical Properties
| Molecular Formula | C20H19N3O.CH4O3S | |
| Molecular Weight | 413.49 | |
| Exact Mass | 413.14 | |
| Elemental Analysis | C, 61.00; H, 5.61; N, 10.16; O, 15.48; S, 7.75 | |
| CAS # | 803712-79-0 | |
| Related CAS # | Obatoclax;803712-67-6 | |
| PubChem CID | 16681698 | |
| Appearance | Solid powder | |
| LogP | 4.507 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 29 | |
| Complexity | 869 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | S(C([H])([H])[H])(=O)(=O)O[H].O(C([H])([H])[H])C1=C([H])/C(=C2\C([H])=C3C([H])=C([H])C([H])=C([H])C3=N\2)/N([H])/C/1=C(\[H])/C1=C(C([H])([H])[H])C([H])=C(C([H])([H])[H])N1[H] |
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| InChi Key | ZFKXDVMHNXPEIY-PEZBNFGJSA-N | |
| InChi Code | InChI=1S/C20H19N3O.CH4O3S/c1-12-8-13(2)21-16(12)10-19-20(24-3)11-18(23-19)17-9-14-6-4-5-7-15(14)22-17;1-5(2,3)4/h4-11,21-22H,1-3H3;1H3,(H,2,3,4)/b19-10-; | |
| Chemical Name | (Z)-2-(2-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-3-methoxy-2H-pyrrol-5-yl)-1H-indole methanesulfonate | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Bcl-2 (Ki=220 nM); Mcl-1 (Ki=1-7 μM); Bcl-xL (Ki=1-7 μM); Bcl-W (Ki=1-7 μM); Bcl-B (Ki=1-7 μM) | |||
| ln Vitro | Obatoclax Mesylate (GX15-070 Mesylate) inhibits BCL-2, BCL-XL, MCL-1, BCL-w, A1, and BCL-b with Ki values≈1-7 μM[2]. Obatoclax Mesylate (50-200 nM; 24-72 hours) induces a dose- and time-dependent reduction of cell numbers in all human colorectal cancer cell lines. Particularly, for HCT116, HT-29, and LoVo cells, the IC50 for cell proliferation at 72 h is 25.85, 40.69, and 40.01 nM, respectively[1]. Obatoclax Mesylate (400 nM; for 24 hours) induces autophagy in OSCC cells[3]. Obatoclax Mesylate (50-200 nM; for 24 hours) provokes a dose-dependent increase in the G1-phase cell populations[1]. ?Obatoclax Mesylate (25-200 nM; for 24 hours) indicates a marked drop in cyclin D1 levels as low as 50 nM[1]. Obatoclax Mesylate causes cyclin D1 to degrade in either a T286 phosphorylation-dependent or -independent manner. The steady-state levels of p-Cyclin D (T286) in HCT116 and LoVo cells started to decrease after exposure to obatoclax Mesylate (200 nM; 1, 3, 6, 12, 24 hours). In HT-29 cells, obatoclax mesylate barely affects ERK1/2 activity while inhibiting GSK3 and activating p38MAPK[1]. Obatoclax Mesylate (50-450 nM) potently inhibits the clonogenic potential of oral cancer cells[1]. | |||
| ln Vivo | Obatoclax Mesylate (GX15-070 Mesylate; 1.15-5 mg/kg; intravenously injected; five consecutive days) In xenograft mouse models, Obatoclax Mesylate demonstrates potent antitumor activity in a dose-dependent manner[4]. | |||
| Enzyme Assay | 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 | 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 Protocol |
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| References |
[1]. Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells. Int J Mol Sci. 2016 Dec 27;18(1). 2]. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19512-7. Epub 2007 Nov 26. [3]. BH3 mimetic Obatoclax (GX15-070) mediates mitochondrial stress predominantly via MCL-1 inhibition and induces autophagy-dependent necroptosis in human oral cancer cells. Oncotarget. 2016 Aug 5;8(36):60060-60079. [4]. Identification of anisomycin, prodigiosin and obatoclax as compounds with broad-spectrum anti-parasitic activity. PLoS Negl Trop Dis. 2020 Mar 20;14(3):e0008150. |
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| Additional Infomation | Obatoclax Mesylate is the mesylate salt of obatoclax, a synthetic small-molecule inhibitor of the bcl-2 family of proteins with potential pro-apoptotic and antineoplastic activities. Obatoclax binds to members of the Bcl-2 protein family, preventing the binding of these anti-apoptotic proteins to the pro-apoptotic proteins Bax and Bak and so promoting the activation of the apoptotic pathway in Bcl-2-overexpressing cells. The Bcl-2 family of proteins (bcl-2, bcl-xl, bcl-w, and Mcl-1) are overexpressed in a wide variety of cancers, including those of the lymphatic system, breast, lung, prostate, and colon. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (2.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (2.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4184 mL | 12.0922 mL | 24.1844 mL | |
| 5 mM | 0.4837 mL | 2.4184 mL | 4.8369 mL | |
| 10 mM | 0.2418 mL | 1.2092 mL | 2.4184 mL |