(R)-(-)-Gossypol acetic acid

SKU: orb1300804

Description

(R)-(-)-Gossypol acetic acid

Research Area

Cell Biology

Key Properties

• CAS Number: 866541-93-7
• MW: 578.61
• Purity: 98.88%
• Formula: C₃₀H₃₀O₈·C₂H₄O₂
• SMILES: CC(O)=O.CC(C)c1c(O)c(O)c(C=O)c2c(O)c(c(C)cc12)-c1c(C)cc2c(C(C)C)c(O)c(O)c(C=O)c2c1O
• Target: Bcl-2 Family,Autophagy
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:107 mg/mL (184.93 mM);Ethanol:82 mg/mL (141.72 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (5.7 mM)

Bioactivity

• Target IC50:
  Bcl-2:0.32 μM(Ki)|BCL-XL:0.48 μM(Ki)|MCL1:0.18 μM(Ki)
• In Vivo:
  AT-101 is still detectable in plasma with average concentrations of 0.49 μM for the 35 mg/kg group and 0.39 μM for the 200 mg/kg group in SCID beige mice bearing RL-DLBCL xenograft. AT-101 peak plasma concentration is observed after 30 minutes of administration of the drug in both the dose levels, with the 200 mg/kg group showing a plasma average concentration almost 4 times greater than the 35 mg/kg group (7.88 μM and 27.78 μM respectively) in SCID beige mice. AT-101 (25 mg/kg to 100 mg/kg, orally) indefinitely results in earlier onset of weight loss equivalent to more than 10% of the pretreatment weight and death in SCID beige mice. AT-101 (35 mg/kg, orally per day for 10 days) plus intraperitoneal cyclophosphamide (Cy) and intraperitoneal rituximab (R) show significantitumor volume control compared to any other treatment group. AT-101 (15 mg/kg, p.o., 5 days/week) as a single agent in intact mice significantly reduces the development of VCaP tumor growth compared to untreated tumors at weeks 2 to 6. AT-101 in combination with surgical castration delays the onset of androgen-independent VCaP tumor growth compared to castration-only or AT-101-only groups in mice.
• In Vitro:
  AT-101 inhibits a panel of different lymphoproliferative malignancies with IC50 ranged from 1.2 μM to 7.4 μM. AT-101 (10 μM) disrupts the Δψm in a concentration- and time-dependent manner in a diffuse large B-cell and in mantle cell lymphoma lines. AT-101 (1 μM or 2 μM) combined with carfilzomib (6 nM or 10 nM) induces apoptosis in HBL-2 and Granta cell lines. AT-101 (20 μM for 24 hours) results in a median 72% apoptosis and down-regulation of Mcl-1 in CLL lymphocytes in both suspension culture as well as stromal coculture. Stromal cells express undetectable levels of antiapoptotic but high levels of activated ERK and AKT proteins and has low or no apoptosis with AT-101. AT-101 induces apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 mM and 2.4 mM in Jurkat T and U937 cells, respectively. AT-101 (10 μM) combined with radiation (32 Gy) induces more apoptosis than radiation alone and exceeds the sum of the effects caused by the single agent treatments. AT-101 activates SAPK/JNK in a dose- and time-dependent manner. AT-101 (10 μM) induces apoptosis through activation of caspase-9, -3, and -7 in VCaP Cells. AT-101 (10 μM) decreases Bcl-2 and Mcl-1 expression in VCaP cells. AT-101 (< 20 μM) is able to inhibit the growth of multiple myeloma cells despite the stimulatory growth effects provided by stromal cells in the bone marrow milieu. AT-101 (10 μM) induces apoptosis in multiple myeloma cells via the activation of caspases 3, caspases 9 and PARP. AT-101 (10 μM) promotes apoptosis in multiple myeloma cells by disrupting the Bax/Bcl-2 ratio and the mitochondrial membrane potential.
• Cell Research:
  Cells are counted and resuspended at an approximate concentration of 3×105 cells/well in a 24-well plate. AT-101 is diluted in DMSO that is maintained at a final concentration of less than 0.5%. Concentrations of AT-101 from 1 nM to 10 μM are used in most experiments. Following incubation at 37 ℃ in a 5% CO2 humidified incubator, 100 μL from each well is transferred to a 96-well opaque-walled plate; cell-Titer-Glo Reagent is added in a 1:1 ratio. Contents are mixed for 2 minutes on an orbital shaker to induce cell lysis. The plates are allowed to incubate at room temperature for 10 minutes before recording luminescence with a Synergy HT Multi-Detection Microplate Reader. In the schedule dependency experiments, serial dilutions of each drug are prepared in ratios relative to their IC50. Cells are preincubated with AT-101 for up to 72 hours, while 4-HC is added for a 24-hour period, being added at time 0, 24 hours, and 48 hours from the start of incubation. Each experiment is performed in triplicate and repeated at least twice.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Mcl-1, Gossypol acetic acid, (R) ( ) Gossypol acetic acid, (R)()Gossypol acetic acid, (-)-Gossypol acetic acid, (R)-Gossypol acetic acid, acetic acid, Autophagy, AT 101 Acetate, AT 101, AT-101, AT-101 (acetic acid), AT-101 Acetate, AT101 acetic acid, Bcl-2 Family, Bcl-xL, Bcl-2

Compound Identifiers

PubChem CID

227456