AT-101
AT-101 is the orally bioavailable the R-(-) enantiomer of gossypol with potential antineoplastic activity. As a BH3 mimetic, R-(-)-gossypol binds to the hydrophobic surface binding groove BH3 of the anti-apoptotic proteins Bcl-2 and Bcl-xL, blocking their heterodimerization with pro-apoptotic members of the Bcl-2 family of proteins such as Bad, Bid, and Bim; this may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Racemic gossypol is a polyphenolic compound isolated from cottonseed.
1: Spijkers-Hagelstein JA, Schneider P, Pinhanços SM, Garrido Castro P, Pieters R, Stam RW. Glucocorticoid sensitisation in Mixed Lineage Leukaemia-rearranged acute lymphoblastic leukaemia by the pan-BCL-2 family inhibitors gossypol and AT-101. Eur J Cancer. 2014 Jun;50(9):1665-74. doi: 10.1016/j.ejca.2014.03.011. Epub 2014 Apr 3. PubMed PMID: 24703900.
2: Li G, Liu L, Shan C, Cheng Q, Budhraja A, Zhou T, Cui H, Gao N. RhoA/ROCK/PTEN signaling is involved in AT-101-mediated apoptosis in human leukemia cells in vitro and in vivo. Cell Death Dis. 2014 Jan 16;5:e998. doi: 10.1038/cddis.2013.519. PubMed PMID: 24434521; PubMed Central PMCID: PMC4040709.
3: Mei H, Lin Z, Wang Y, Wu G, Song Y. Autophagy inhibition enhances pan-Bcl-2 inhibitor AT-101-induced apoptosis in non-small cell lung cancer. Neoplasma. 2014;61(2):186-92. doi: 10.4149/neo_2014_024. PubMed PMID: 24299314.
4: Paulus A, Chitta K, Akhtar S, Personett D, Miller KC, Thompson KJ, Carr J, Kumar S, Roy V, Ansell SM, Mikhael JR, Dispenzieri A, Reeder CB, Rivera CE, Foran J, Chanan-Khan A. AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia. Br J Haematol. 2014 Feb;164(3):352-65. doi: 10.1111/bjh.12633. Epub 2013 Nov 17. PubMed PMID: 24236538.
5: Lane R. Bill Frankland: active allergist at 101. Lancet. 2013 Aug 31;382(9894):762. doi: 10.1016/S0140-6736(13)61821-8. PubMed PMID: 23993179.
6: Schelman WR, Mohammed TA, Traynor AM, Kolesar JM, Marnocha RM, Eickhoff J, Keppen M, Alberti DB, Wilding G, Takebe N, Liu G. A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Invest New Drugs. 2014 Apr;32(2):295-302. doi: 10.1007/s10637-013-9999-7. Epub 2013 Jul 17. PubMed PMID: 23860642; PubMed Central PMCID: PMC3895103.
7: Al Moamen NJ, Mahdi F, Salman E, Ahmed T, Abbas R, Al Arrayed S, Sanad H, Ahmed AA. Silent β-thalassemia mutations at -101 (C>T) and -71 (C>T) and their coinheritance with the sickle cell mutation in Bahrain. Hemoglobin. 2013;37(4):369-77. doi: 10.3109/03630269.2013.785434. Epub 2013 Apr 15. PubMed PMID: 23586372.
8: Karaca B, Atmaca H, Bozkurt E, Kisim A, Uzunoglu S, Karabulut B, Sezgin C, Sanli UA, Uslu R. Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells. Mol Biol Rep. 2013 Jun;40(6):3925-33. doi: 10.1007/s11033-012-2469-z. Epub 2012 Dec 27. PubMed PMID: 23269627.
9: Thakur A, Lum LG, Schalk D, Azmi A, Banerjee S, Sarkar FH, Mohommad R. Pan-Bcl-2 inhibitor AT-101 enhances tumor cell killing by EGFR targeted T cells. PLoS One. 2012;7(11):e47520. doi: 10.1371/journal.pone.0047520. Epub 2012 Nov 19. PubMed PMID: 23185240; PubMed Central PMCID: PMC3501501.
10: Kisim A, Atmaca H, Cakar B, Karabulut B, Sezgin C, Uzunoglu S, Uslu R, Karaca B. Pretreatment with AT-101 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing death receptors 4 and 5 protein levels. J Cancer Res Clin Oncol. 2012 Jul;138(7):1155-63. doi: 10.1007/s00432-012-1187-1. Epub 2012 Mar 13. PubMed PMID: 22411600.
2: Li G, Liu L, Shan C, Cheng Q, Budhraja A, Zhou T, Cui H, Gao N. RhoA/ROCK/PTEN signaling is involved in AT-101-mediated apoptosis in human leukemia cells in vitro and in vivo. Cell Death Dis. 2014 Jan 16;5:e998. doi: 10.1038/cddis.2013.519. PubMed PMID: 24434521; PubMed Central PMCID: PMC4040709.
3: Mei H, Lin Z, Wang Y, Wu G, Song Y. Autophagy inhibition enhances pan-Bcl-2 inhibitor AT-101-induced apoptosis in non-small cell lung cancer. Neoplasma. 2014;61(2):186-92. doi: 10.4149/neo_2014_024. PubMed PMID: 24299314.
4: Paulus A, Chitta K, Akhtar S, Personett D, Miller KC, Thompson KJ, Carr J, Kumar S, Roy V, Ansell SM, Mikhael JR, Dispenzieri A, Reeder CB, Rivera CE, Foran J, Chanan-Khan A. AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia. Br J Haematol. 2014 Feb;164(3):352-65. doi: 10.1111/bjh.12633. Epub 2013 Nov 17. PubMed PMID: 24236538.
5: Lane R. Bill Frankland: active allergist at 101. Lancet. 2013 Aug 31;382(9894):762. doi: 10.1016/S0140-6736(13)61821-8. PubMed PMID: 23993179.
6: Schelman WR, Mohammed TA, Traynor AM, Kolesar JM, Marnocha RM, Eickhoff J, Keppen M, Alberti DB, Wilding G, Takebe N, Liu G. A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Invest New Drugs. 2014 Apr;32(2):295-302. doi: 10.1007/s10637-013-9999-7. Epub 2013 Jul 17. PubMed PMID: 23860642; PubMed Central PMCID: PMC3895103.
7: Al Moamen NJ, Mahdi F, Salman E, Ahmed T, Abbas R, Al Arrayed S, Sanad H, Ahmed AA. Silent β-thalassemia mutations at -101 (C>T) and -71 (C>T) and their coinheritance with the sickle cell mutation in Bahrain. Hemoglobin. 2013;37(4):369-77. doi: 10.3109/03630269.2013.785434. Epub 2013 Apr 15. PubMed PMID: 23586372.
8: Karaca B, Atmaca H, Bozkurt E, Kisim A, Uzunoglu S, Karabulut B, Sezgin C, Sanli UA, Uslu R. Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells. Mol Biol Rep. 2013 Jun;40(6):3925-33. doi: 10.1007/s11033-012-2469-z. Epub 2012 Dec 27. PubMed PMID: 23269627.
9: Thakur A, Lum LG, Schalk D, Azmi A, Banerjee S, Sarkar FH, Mohommad R. Pan-Bcl-2 inhibitor AT-101 enhances tumor cell killing by EGFR targeted T cells. PLoS One. 2012;7(11):e47520. doi: 10.1371/journal.pone.0047520. Epub 2012 Nov 19. PubMed PMID: 23185240; PubMed Central PMCID: PMC3501501.
10: Kisim A, Atmaca H, Cakar B, Karabulut B, Sezgin C, Uzunoglu S, Uslu R, Karaca B. Pretreatment with AT-101 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing death receptors 4 and 5 protein levels. J Cancer Res Clin Oncol. 2012 Jul;138(7):1155-63. doi: 10.1007/s00432-012-1187-1. Epub 2012 Mar 13. PubMed PMID: 22411600.
| Chemical | |
|---|---|
| CAS Num | 90141-22-3AT-101 |
| Chemical Formula | C30H30O8 |
| Molecular Weight | 518.55 |
| IUPAC Chemical Name | (-)-1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde |
| Exact Mass | 518.19407 |
| Elemental Analysis | C, 69.49; H, 5.83; O, 24.68 |
| Synonym | AT101; AT-101; AT 101; Gossypol. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=CC1=C(O)C(O)=C(C(C)C)C2=CC(C)=C(C3=C(C)C=C4C(C(C)C)=C(O)C(O)=C(C=O)C4=C3O)C(O)=C12 |
| Biological | |
| Pathways | Apoptosis |
| Physical | |
| Appearance | Solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >2 years if stored properly |
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