阿伏西地

阿伏西地
	IUPAC名; 2′-Chloro-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]flavone
	系統名; 2-(2-Chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4H-1-benzopyran-4-one
別名	Flavopiridol, HMR 1275, L-868275
識別
CAS號	146426-40-6
PubChem	5287969
ChemSpider	4450222
SMILES	Clc4ccccc4C=2Oc1c(c(O)cc(O)c1C(=O)C=2)[C@H]3CCN(C)C[C@H]3O;
ChEBI	47344
DrugBank	DB03496
KEGG	D09868
MeSH	Flavopiridol
IUPHAR配體	5680
性質
化學式	C21H20ClNO5
摩爾質量	401.8402 g·mol⁻¹
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

阿伏西地（INN：alvocidib；開發代號：HMR 1275、L-868275），也叫夫拉平度（flavopiridol），是一種黃酮類生物鹼（英語：Flavonoid alkaloid）CDK9激酶抑制劑（英語：Protein kinase inhibitor），由Tolero製藥公司進行臨床開發，用於治療急性骨髓性白血病。還研究了將它用於治療關節炎^[1]和粥樣斑塊（英語：Atheroma）形成。^[2]阿伏西地的靶點是正轉錄延伸因子（英語：P-TEFb）（P-TEFb）。^[3]^[4]用阿伏西地處理細胞會抑制P-TEFb並導致mRNA產生的損失。^[5]^[6]

該化合物是羅希吐鹼（西班牙語：Rohitukina）的合成類似物。羅希吐鹼是一種天然產物，最初從山楝中提取，後來從紅果樫木中提取。^[7]^[8]

孤兒藥[編輯]

美國食品藥品監督管理局已授予阿伏西地孤兒藥資格，用於治療急性髓系白血病患者。^[9]

參考資料[編輯]

^ Sekine C, Sugihara T, Miyake S, Hirai H, Yoshida M, Miyasaka N, Kohsaka H. Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors. J. Immunol. 2008, 180 (3): 1954–61. PMID 18209094. doi:10.4049/jimmunol.180.3.1954 .
^ Ruef J, Meshel AS, Hu Z, Horaist C, Ballinger CA, Thompson LJ, Subbarao VD, Dumont JA, Patterson C. Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation In vivo after carotid injury in the rat. Circulation. 1999, 100 (6): 659–65. PMID 10441105. doi:10.1161/01.cir.100.6.659 .
^ Chao SH, Fujinaga K, Marion JE, Taube R, Sausville EA, Senderowicz AM, Peterlin BM, Price DH. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J. Biol. Chem. 2000, 275 (37): 28345–8. PMID 10906320. doi:10.1074/jbc.C000446200 .
^ Chao SH, Price DH. Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J. Biol. Chem. 2001, 276 (34): 31793–9. PMID 11431468. doi:10.1074/jbc.M102306200 .
^ Cheng B, Li T, Rahl PB, Adamson TE, Loudas NB, Guo J, Varzavand K, Cooper JJ, Hu X, Gnatt A, Young RA, Price DH. Functional association of Gdown1 with RNA polymerase II poised on human genes. Mol. Cell. 2012, 45 (1): 38–50. PMC 3259526 . PMID 22244331. doi:10.1016/j.molcel.2011.10.022.
^ Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA. c-Myc regulates transcriptional pause release. Cell. 2010, 141 (3): 432–45. PMC 2864022 . PMID 20434984. doi:10.1016/j.cell.2010.03.030.
^ Harmon, AD; Weiss, U; Silverton, JV. The structure of rohitukine, the main alkaloid of Amoora rohituka (syn.Aphanamixis polystachya) (Meliaceae). Tetrahedron Lett. 1979, 20 (1): 721–724. doi:10.1016/S0040-4039(01)93556-7.
^ Lakdawala, AD; Shirole, MV; Mandrekar, SS; Dohadwalla, AN. Immunopharmacological potential of rohitukine: a novel compound isolated from the plant Dysoxylum binectariferum. Asia Pac J Pharmcol. 1988, 3 (1): 91–98.
^ FDA grants orphan drug status to Alvocidib for AML.

[pmid18209094-1] Sekine C, Sugihara T, Miyake S, Hirai H, Yoshida M, Miyasaka N, Kohsaka H. Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors. J. Immunol. 2008, 180 (3): 1954–61. PMID 18209094. doi:10.4049/jimmunol.180.3.1954 .

[pmid10441105-2] Ruef J, Meshel AS, Hu Z, Horaist C, Ballinger CA, Thompson LJ, Subbarao VD, Dumont JA, Patterson C. Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation In vivo after carotid injury in the rat. Circulation. 1999, 100 (6): 659–65. PMID 10441105. doi:10.1161/01.cir.100.6.659 .

[pmid10906320-3] Chao SH, Fujinaga K, Marion JE, Taube R, Sausville EA, Senderowicz AM, Peterlin BM, Price DH. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J. Biol. Chem. 2000, 275 (37): 28345–8. PMID 10906320. doi:10.1074/jbc.C000446200 .

[pmid11431468-4] Chao SH, Price DH. Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J. Biol. Chem. 2001, 276 (34): 31793–9. PMID 11431468. doi:10.1074/jbc.M102306200 .

[pmid22244331-5] Cheng B, Li T, Rahl PB, Adamson TE, Loudas NB, Guo J, Varzavand K, Cooper JJ, Hu X, Gnatt A, Young RA, Price DH. Functional association of Gdown1 with RNA polymerase II poised on human genes. Mol. Cell. 2012, 45 (1): 38–50. PMC 3259526 . PMID 22244331. doi:10.1016/j.molcel.2011.10.022.

[pmid20434984-6] Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA. c-Myc regulates transcriptional pause release. Cell. 2010, 141 (3): 432–45. PMC 2864022 . PMID 20434984. doi:10.1016/j.cell.2010.03.030.

[7] Harmon, AD; Weiss, U; Silverton, JV. The structure of rohitukine, the main alkaloid of Amoora rohituka (syn.Aphanamixis polystachya) (Meliaceae). Tetrahedron Lett. 1979, 20 (1): 721–724. doi:10.1016/S0040-4039(01)93556-7.

[8] Lakdawala, AD; Shirole, MV; Mandrekar, SS; Dohadwalla, AN. Immunopharmacological potential of rohitukine: a novel compound isolated from the plant Dysoxylum binectariferum. Asia Pac J Pharmcol. 1988, 3 (1): 91–98.

[9] FDA grants orphan drug status to Alvocidib for AML.

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