CAS 90141-22-3|AT-101
Introduction：Basic information about CAS 90141-22-3|AT-101, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | AT-101 | ||
|---|---|---|---|
| CAS Number | 90141-22-3 | Molecular Weight | 518.554 |
| Density | 1.4±0.1 g/cm3 | Boiling Point | 707.9±55.0 °C at 760 mmHg |
| Molecular Formula | C30H30O8 | Melting Point | 166-167ºC |
| MSDS | USA | Flash Point | 395.9±28.0 °C |
Names
| Name | (R)-(-)-Gossypol |
|---|---|
| Synonym | More Synonyms |
AT-101 BiologicalActivity
| Description | (R)-(-)-Gossypol (AT-101) is the levorotatory isomer of a natural product Gossypol. 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. |
|---|---|
| Related Catalog | Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Apoptosis >>Bcl-2 FamilyResearch Areas >>CancerNatural Products >>Phenols |
| Target | Bcl-2:260 nM (Ki) Bcl-xL:480 nM (Ki) Mcl-1:170 nM (Ki) Autophagy |
| In Vitro | The natural racemic Gossypol has two enantiomers, namely the (R)-(-)-Gossypol (AT-101) and (+)-Gossypol enantiomers. (R)-(-)-Gossypol (AT-101) and (+)-Gossypol binds to Bcl-2 or Bcl-xL with similar binding affinities, AT-101 is more potent than (+)-Gossypol in inhibition of cell growth and induction of apoptosis, possibly due to the influence of serum in the cell culture experiments. The racemic form and each of the enantiomers of Gossypol are tested against UM-SCC-6 and UM-SCC-14A in 6-day MTT assays. AT-101 exhibits greater growth inhibition relative to (±)-Gossypol than (+)-Gossypol in both cell lines tested (P<0.001). An intermediate growth inhibitory effect is observed with (±)-Gossypol but this effect is only observed at the higher dose of Gossypol (10 μM, P<0.0001). (R)-(-)-Gossypol (AT-101) binds to the BH3-binding groove of Bcl-xL and Bcl-2 proteins with fairly high affinity, has potent activity against head and neck squamous cell carcinomas (HNSCC) cell lines in vitro. Furthermore, it induces apoptosis with high efficiency in HNSCC tumor cells that express functional p53 and that also kills tumor cells with mutant p53 by a different mechanism. AT-101 doses required to inhibit the growth of human fibroblast cell lines by 50% were 2- to 10-fold higher than for HNSCC cell lines. To inhibit human oral keratinocyte growth by 50%, (R)-(-)-Gossypol (AT-101) concentrations are 2-to 3-fold higher than for HNSCC cell lines. (R)-(-)-Gossypol (AT-101) causes dose-dependent inhibition of cell growth in ten UM-SCC cell lines over a range from 0.5 to 10 μM in a 6-day MTT assay. The relative sensitivity of the cell lines vary from a very sensitive group with an IC50 of 2-5 μM and a less sensitive group with IC50 clusters around 10 μM[1]. (R)-(-)-Gossypol (AT-101) is determined to bind to Bcl-2, Mcl-1 and Bcl-xL proteins with Ki values of 260±30 nM, 170±10 nM, and 480±40 nM, respectively[2]. |
| Cell Assay | Two representative UM-SCC cell lines, UM-SCC-6 and UM-SCC-14A, are continuously exposed to 0 (vehicle control), 5 or 10 μM (±)-Gossypol, (R)-(-)-Gossypol or (+)-Gossypol in a 6-day MTT cell survival assay[1]. |
| 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. |
Chemical & Physical Properties
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 707.9±55.0 °C at 760 mmHg |
| Melting Point | 166-167ºC |
| Molecular Formula | C30H30O8 |
| Molecular Weight | 518.554 |
| Flash Point | 395.9±28.0 °C |
| Exact Mass | 518.194092 |
| PSA | 155.52000 |
| LogP | 6.16 |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.742 |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 210 mg/kg
- SEX/DURATION :
- male 2 week(s) pre-mating
- TOXIC EFFECTS :
- Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)
- REFERENCE :
- JOETD7 Journal of Ethnopharmacology. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1979- Volume(issue)/page/year: 20,21,1987
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 320 mg/kg
- SEX/DURATION :
- male 40 day(s) pre-mating
- TOXIC EFFECTS :
- Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)
- REFERENCE :
- CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 31,141,1985
Safety Information
| RIDADR | NONH for all modes of transport |
|---|
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Synonyms
| 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl[2,2'-binaphthalene]-8,8'-dicarboxaldehyde |
| UNII:XNA7DR63CQ |
| 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene-8,8'-dicarbaldehyde |
| UNII:8DY2X8LXW4 |
| 2,2'-Bis[1,6,7-trihydroxy-3-methyl-5-isopropyl-8-aldehydonaphthalene] |
| 1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalene-8,8'-dicarbaldehyde |
| Gossypol |
| UNII:KAV15B369O |
| 2,2'-bis[8-formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene] |
| (-)-1,1',6,6',7,7'-Hexahydroxy-3,3'-dimethyl-5,5'-bis(1-methylethyl)[2,2'-binaphthalene]-8,8'-dicarboxaldehyde |
| 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalen-8,8'-dicarbaldehyd |
| [2,2'-Binaphthalene]-8,8'-dicarboxaldehyde, 1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-bis(1-methylethyl)- |
| 1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-bis(1-methylethyl)-2,2'-binaphthalene-8,8'-dicarbaldehyde |
| 1,1',6,6',7,7'-Hexahydroxy-3,3'-dimethyl-5,5'-bis(1-methylethyl)[2,2'-binaphthalene]-8,8'-dicarboxaldehyde |
| AT-101 |
