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| Targets |
Bcl-2 family proteins (including Bcl-2, Bcl-xL, Mcl-1, and others). Obatoclax is a small-molecule inhibitor that binds to anti-apoptotic Bcl-2 proteins and interferes with their ability to interact with pro-apoptotic proteins. As a BH3 mimetic, Obatoclax mimics the action of BH3-only proteins, which are pro-apoptotic members of the Bcl-2 family. By binding to anti-apoptotic Bcl-2 proteins, Obatoclax displaces pro-apoptotic proteins such as Bax and Bak, allowing them to oligomerize and induce mitochondrial outer membrane permeabilization, leading to apoptosis. The compound targets multiple anti-apoptotic Bcl-2 family members, including Bcl-2, Bcl-xL, and Mcl-1.
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| ln Vitro |
Obatoclax (GX15-070) has a Ki value of around 1-7 μM and inhibits BCL-2, BCL-XL, MCL-1, BCL-w, A1, and BCL-b [2]. In all human colorectal cancer cell lines, obatoclax (50-200 nM; 24-72 hours) causes dose- and time-dependent decreases in cell number. Specifically, at 72 hours, the IC50 values for cell proliferation of HCT116, HT-29, and LoVo cells were 25.85, 40.69, and 40.01 nM, respectively [1]. For a duration of 24 hours, obatoclax (400 nM) stimulates autophagy in OSCC cells [3]. The dose-dependent rise in the G1 cell population is brought about by obatoclax (50-200 nM) for a 24-hour period [1]. Cyclin D1 levels are significantly reduced by obatoclax (25-200 nM; for 24 hours); the lowest level observed was 50 nM [1]. Obatoclax causes cyclin D1 degradation that is either -independent or -dependent on T286 phosphorylation. After being exposed to obatoclax (200 nM; 1, 3, 6, 12, 24 hours), steady-state levels of p-Cyclin D (T286) in HCT116 and LoVo cells started to decline. In HT-29 cells, obatoclax hardly affects ERK1/2 activity but inhibits GSK3β and activates p38 MAPK [1]. The clonogenic potential of oral cancer cells is successfully inhibited by obatoclax (50, 100, 150, 200, 250, 300, 350, 400, 450 nM) [1].
Obatoclax demonstrates potent in vitro activity against various cancer cell lines. In human colorectal cancer cell lines, Obatoclax (50-200 nM; 24-72 hours) induces a dose- and time-dependent reduction of cell numbers. The IC50 for cell proliferation at 72 hours is 25.85 nM in some cell lines. The compound induces apoptosis in cancer cells by disrupting the interaction between anti-apoptotic and pro-apoptotic Bcl-2 family proteins. Obatoclax has been evaluated in various cancer types, including leukemia, lymphoma, and solid tumors. Further detailed in vitro data, including IC50 values against various cancer cell lines, are available in the primary literature. |
| ln Vivo |
In a xenograft mouse model, obatoclax (GX15-070; 1.15–5 mg/kg; intravenous injection; five consecutive days) exhibited strong anticancer efficacy in a dose-dependent manner [4].
In vivo activity of Obatoclax has been investigated in preclinical models of various cancers. The compound has shown antitumor activity in xenograft models of leukemia, lymphoma, and solid tumors. However, specific in vivo data, including efficacy in animal models, pharmacokinetics, and toxicity, are not extensively detailed in the available literature summary. Obatoclax has also been evaluated in clinical trials for various malignancies. Further information would be available in the primary research publications. |
| Enzyme Assay |
Binding assays for Obatoclax are performed using recombinant Bcl-2 family proteins. The compound is incubated with the protein and a fluorescently labeled BH3 peptide, and the inhibition of peptide binding is measured. Binding affinities for various Bcl-2 family members (Bcl-2, Bcl-xL, Mcl-1) are determined. The compound's ability to disrupt Bcl-2 family protein interactions can be confirmed in cell-based assays.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: Human colorectal cancer HCT116, HT-29 and LoVo Cell Tested Concentrations: 50, 100, 200 nM Incubation Duration: 24, 48 and 72 hrs (hours) Experimental Results: Induced dose- and time-dependent reduction in cell proliferation Number of cells. Autophagy assay [3] Cell Types: AW8507 and SCC029B Cell Tested Concentrations: 400 nM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of autophagy in OSCC cells. Cell cycle analysis[1] Cell Types: HCT116 and HT-29 Cell Tested Concentrations: 50, 100, 200 nM Incubation Duration: 24 hrs (hours) Experimental Results: Caused a dose-dependent increase in the G1 phase cell population. Western Blot Analysis[1] Cell Types: HCT116, HT-29 and LoVo Cell Tested Concentrations: 50, 100, 200 nM Incubation Duration: 24 hrs (hours) Experimental Results: Demonstrated significant decrease in cyclin D1 levels, as low as 50 nM. Cell-based assays for Obatoclax are conducted using various cancer cell lines. Cells are treated with the compound at various concentrations (typically 50-200 nM) for defined time periods (24-72 hours), and the following endpoints are assessed: cell viability (by MTT or CellTiter-Glo), apoptosis (by annexin V staining, caspase activation, or PARP cleavage), and mitochondrial membrane potential (by fluorescent dyes). The compound's ability to induce apoptosis is evaluated. The IC50 for cell proliferation is determined from dose-response curves. |
| Animal Protocol |
Animal/Disease Models: 6-8 weeks old female subcutaneoustumor BALB/C nude mice [4]
Doses: 1.15, 2.5, 5 mg/kg Route of Administration: intravenous (iv) (iv)injection (through tail vein); five days (i.e. 5 injections ) Experimental Results: Demonstrated potent antitumor activity in a dose-dependent manner in xenograft mouse models. In vivo studies for Obatoclax are performed in mouse xenograft models of various cancers. The compound is typically administered via various routes at various doses and schedules. Pharmacodynamic endpoints include measurement of apoptosis markers in tumor tissues and evaluation of tumor growth inhibition. Pharmacokinetic parameters such as plasma concentration-time profiles, half-life, clearance, and bioavailability are determined from serial blood sampling. |
| ADME/Pharmacokinetics |
Obatoclax has been characterized in preclinical pharmacokinetic studies. The compound's molecular weight is 317.38 and its molecular formula is C20H19N3O. Storage recommendations include appropriate temperature control to maintain stability. The compound is soluble in DMSO and other organic solvents.
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| Toxicity/Toxicokinetics |
In clinical trials, Obatoclax has shown manageable toxicity, though specific toxicity data are not detailed in the available summary. Common side effects may include infusion-related reactions and gastrointestinal effects. The compound is intended for research use and has been evaluated in clinical trials.
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| References |
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| Additional Infomation |
Obatoclax has been used in clinical trials for various diseases, including acute myeloid leukemia (AML), leukemia, myelofibrosis, Hodgkin's lymphoma, and mantle cell lymphoma. Obatoclax is a small molecule drug that acts as a pan-inhibitor of the Bcl-2 family of proteins and possesses pro-apoptotic activity. GX015-070 is a selective antagonist of the BH3 binding groove of Bcl-2 family proteins, which are frequently overexpressed in various cancers, including chronic lymphocytic leukemia (CLL). This drug induces/restores apoptosis in cancer cells by simultaneously inhibiting apoptosis-inhibiting factors in multiple members of the Bcl-2 family. Mechanism of Action: Obatoclax binds to anti-apoptotic Bcl-2 proteins, interfering with their interaction with pro-apoptotic proteins.
Obatoclax is a small-molecule inhibitor of the Bcl-2 family of proteins that induces apoptosis in cancer cells. It has been investigated as a potential anticancer agent for various malignancies. The compound is not FDA-approved for any indication. Synonyms include GX15-070. The compound is available for research purposes from multiple chemical suppliers. |
| Molecular Formula |
C20H19N3O
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|---|---|
| Molecular Weight |
317.384364366531
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| Exact Mass |
317.152
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| CAS # |
803712-67-6
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| Related CAS # |
Obatoclax Mesylate;803712-79-0
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| PubChem CID |
11404337
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| Appearance |
Light brown to brown solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
570.5±50.0 °C at 760 mmHg
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| Flash Point |
298.8±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.652
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| LogP |
3.89
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
777
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(N1)/C=C\2/C(=C/C(=C/3\C=C4C=CC=CC4=N3)/N2)OC)C
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| InChi Key |
RFTSSZJZXOSICM-GRSHGNNSSA-N
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| InChi Code |
InChI=1S/C20H19N3O/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/h4-11,21-22H,1-3H3/b19-10-
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| Chemical Name |
1H-indole, 2-(2-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-3-methoxy-2H-pyrrol-5-yl)-
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| Synonyms |
GX15-070; GX-05-070; GX 15-070; Obatoclax; 803712-67-6; CHEMBL408194; (2Z)-2-[(5Z)-5-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole; 2-(2-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)-3-methoxy-2H-pyrrol-5-yl)-1H-indole; GX05-070; GX 05-070; GX-15-070
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (315.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1508 mL | 15.7540 mL | 31.5080 mL | |
| 5 mM | 0.6302 mL | 3.1508 mL | 6.3016 mL | |
| 10 mM | 0.3151 mL | 1.5754 mL | 3.1508 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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