Obatoclax

SKU: orb1223966

Description

A potent inhibitor of Bcl-2 family with IC50s of 1-7 uM for Bcl-2, Bcl-XL, Bcl-w, Bcl-B, Mcl-1 and Bfl-1; potently interferes with the direct interaction between MCL-1 and BAK in intact mitochondrial outer membrane and inhibited the association between MCL-1 and BAK in intact cells.(In 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.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. In particular, the IC50 of cell proliferation at 72 h are 25.85, 40.69, and 40.01 nM for HCT116, HT-29, and LoVo cells, respectively.Obatoclax Mesylate (400 nM; for 24 hours) induces autophagy in OSCC cells.Obatoclax Mesylate (50-200 nM; for 24 hours) provokes a dose-dependent increase in the G1-phase cell populations.Obatoclax Mesylate (25-200 nM; for 24 hours) indicates a marked drop in cyclin D1 levels as low as 50 nM.Obatoclax Mesylate induces T286 phosphorylation-dependent or -independent cyclin D1 degradation. in HCT116 and LoVo cells, the steady-state levels of p-Cyclin D (T286) began to decline once exposed to obatoclax Mesylate (200 nM; 1, 3, 6, 12, 24 hours). Obatoclax Mesylate inhibits GSK3β but activates p38MAPK, while barely affecting ERK1/2 activity in HT-29 cells.Obatoclax Mesylate (50, 100, 150, 200, 250, 300, 350, 400, 450 nM) potently inhibits the clonogenic potential of oral cancer cells.(In Vivo):Obatoclax Mesylate (GX15-070 Mesylate; 1.15-5 mg/kg; intravenously injected; five consecutive days) exhibits potent antitumor activity in xenograft mouse models in a dose-dependent manner.

Key Properties

• CAS Number: 803712-79-0
• MW: 413.49
• Purity: >98% (HPLC)
• Formula: C₂₁H₂₃N₃O₄S
• SMILES: CC1=CC(=C(N1)/C=C\2/C(=C/C(=C/3\C=C4C=CC=CC4=N3)/N2)OC)C.CS(=O)(=O)O
• Target: Bcl-2
• Solubility: DMSO: ≥ 48.8 mg/mL

Bioactivity

• In Vivo:
  Obatoclax Mesylate (GX15-070 Mesylate; 1.15-5 mg/kg; intravenously injected; five consecutive days) exhibits potent antitumor activity in xenograft mouse models in a dose-dependent manner. Animal model: 6-8 weeks old female BALB/C nude mice bearing subcutaneous tumors. Dosage: 1.15, 2.5, 5 mg/kg. Administration: Intravenously injected (through lateral tail vein); five consecutive days (i. e. 5 injections). Result: Exhibited potent antitumor activity in xenograft mouse models in a dose-dependent manner.
• In 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. 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. In particular, the IC50 of cell proliferation at 72 h are 25.85, 40.69, and 40.01 nM for HCT116, HT-29, and LoVo cells, respectively. Obatoclax Mesylate (400 nM; for 24 hours) induces autophagy in OSCC cells. Obatoclax Mesylate (50-200 nM; for 24 hours) provokes a dose-dependent increase in the G1-phase cell populations. Obatoclax Mesylate (25-200 nM; for 24 hours) indicates a marked drop in cyclin D1 levels as low as 50 nM. Obatoclax Mesylate induces T286 phosphorylation-dependent or -independent cyclin D1 degradation. in HCT116 and LoVo cells, the steady-state levels of p-Cyclin D (T286) began to decline once exposed to obatoclax Mesylate (200 nM; 1, 3, 6, 12, 24 hours). Obatoclax Mesylate inhibits GSK3β but activates p38MAPK, while barely affecting ERK1/2 activity in HT-29 cells. Obatoclax Mesylate (50-450 nM) potently inhibits the clonogenic potential of oral cancer cells. Cell Proliferation Assay Cell line: human colorectal cancer HCT116, HT-29 and LoVo cells. Concentration: 50, 100, 200 nM. Incubation time: 24, 48, and 72 hours. Result: Induced a dose- and time-dependent reduction of cell numbers. Cell Autophagy Assay Cell line: AW8507 and SCC029B cells. Concentration: 400 nM. Incubation time: 24 hours. Result: Induced autophagy in OSCC cells. Cell Cycle Analysis Cell line: HCT116 and HT-29 cells. Concentration: 50, 100, 200 nM. Incubation time: 24 hours. Result: Provoked a dose-dependent increase in the G1-phase cell populations. Western blot analysis. Cell line: HCT116, HT-29 and LoVo cells. Concentration: 25, 50, 100, 200 nM. Incubation time: 24 hours. Result: Indicated a marked drop in cyclin D1 levels as low as 50 nM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Obatoclax Mesylate | GX15-070

Quick Database Links

Gene Symbol

Bcl-2