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(R)-(-)-Gossypol (also known as AT-101) is the levorotatory isomer of Gossypol which is a natural product. AT-101 is determined to bind to Bcl-2, Mcl-1 and Bcl-xL proteins with Kis of 260±30 nM, 170±10 nM, and 480±40 nM, respectively.
| ln Vitro |
The two enantiomers of natural racemic gossypol are (+)-gossypol and (R)-(-)-gossypol (AT-101). The binding affinities of (R)-(-)-gossypol (AT-101) and (+)-gossypol to Bcl-2 or Bcl-xL are similar, although AT-101 is more efficient than (+)-gossypol. The effects of serum in cell culture tests may be the cause of the inhibition of cell growth and activation of apoptosis. In a 6-day MTT experiment, the racemic form of gossypol and each enantiomer were evaluated against UM-SCC-6 and UM-SCC-14A. Between the two cell lines examined, AT-101 showed a higher degree of growth inhibition in comparison to (±)-gossypol as opposed to (+)-gossypol (P<0.001). (±)-gossypol was shown to exhibit moderate growth inhibition; however, this impact was only seen at higher gossypol dosages (10 μM, P<0.0001). (R)-(-)-Gossypol (AT-101) possesses strong anti-head and neck squamous cell carcinoma (HNSCC) cell line activity in vitro and binds to the BH3 binding groove of the Bcl-xL and Bcl-2 proteins with a comparatively high affinity. Furthermore, it has the ability to effectively trigger programmed cell death in HNSCC tumor cells that express functional p53 and eliminate tumor cells that express mutant p53 via distinct processes. When compared to HNSCC cell lines, the amount of AT-101 needed to 50% suppress the development of human fibroblast cell lines was two to ten times more. (R)-(-)-gossypol (AT-101) concentrations were two to three times greater than in HNSCC cell lines in order to 50% decrease human oral keratinocyte development. In a 6-day MTT experiment, 10 UM-SCC cell lines showed a dose-dependent reduction of cell growth in the 0.5 to 10 μM range when treated with (R)-(-)-Gossypol (AT-101). Cell lines exhibit varying degrees of sensitivity; highly sensitive groups have IC50s between 2 and 5 μM, whilst less sensitive groups have IC50s centered around 10 μM [1]. It has been established that (R)-(-)-Gossypol (AT-101) binds to the proteins Bcl-2, Mcl-1, and Bcl-xL, with Ki values of 260±30 nM, 170±10 nM, and 480±40 nM, respectively [2].
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| References |
[1]. Oliver CL, et al. In vitro effects of the BH3 mimetic, (-)-Gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res. 2004 Nov 15;10(22):7757-63.
[2]. Sun Y, et al. Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo. Cancer Biol Ther. 2008 Sep;7(9):1418-26 |
| Molecular Formula |
C₃₀H₃₀O₈
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|---|---|
| Molecular Weight |
518.5544
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| CAS # |
90141-22-3
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| Related CAS # |
(R)-(-)-Gossypol acetic acid;866541-93-7;(S)-Gossypol (acetic acid);1189561-66-7;Gossypol (acetic acid);12542-36-8
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| SMILES |
O=CC1=C2C(O)=C(C3=C(C)C=C4C(C(C)C)=C(O)C(O)=C(C=O)C4=C3O)C(C)=CC2=C(C(C)C)C(O)=C1O
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| InChi Key |
QBKSWRVVCFFDOT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H30O8/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36/h7-12,33-38H,1-6H3
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| Chemical Name |
7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde
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| Synonyms |
AT101AT 101AT-101R-(-)-gossypol acetic acid
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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 Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9285 mL | 9.6423 mL | 19.2845 mL | |
| 5 mM | 0.3857 mL | 1.9285 mL | 3.8569 mL | |
| 10 mM | 0.1928 mL | 0.9642 mL | 1.9285 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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