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AK-2292

PubChem编号: 166594150

有货

库存信息

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库存信息

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货号 (SKU)	包装规格	是否现货	价格	数量
A607472-5mg	5mg	期货
A607472-25mg	25mg	期货

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cereblon signal transducer and activator of transcription 5A

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基本描述

英文名称	AK-2292
别名	AK2292
英文别名	AK2292

名称和标识符

IUPAC Name	[[2-[[(2S)-1-[(2S)-2-[[3-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pent-4-ynyl-methylamino]-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid
INCHI	InChI=1S/C52H54F2N7O10PS2/c1-51(2,3)44(57-46(65)41-29-33-28-34(16-20-40(33)74-41)52(53,54)72(69,70)71)50(68)60-25-9-13-39(60)49(67)59(35-17-14-32(15-18-35)47-55-23-27-73-47)26-22-43(63)58(4)24-7-5-6-10-31-11-8-12-36-37(31)30-61(48(36)66)38-19-21-42(62)56-45(38)64/h8,11-12,14-18,20,23,27-29,38-39,44H,5,7,9,13,19,21-22,24-26,30H2,1-4H3,(H,57,65)(H,56,62,64)(H2,69,70,71)/t38?,39-,44+/m0/s1
InChi Key	LOPYPDQOHNOVBM-QOIUHGAOSA-N
Canonical SMILES	O=C1NC(CCC1N2C(C3=CC=CC(=C3C2)C#CCCCN(C(CCN(C(=O)[C@H]4N(CCC4)C([C@H](C(C)(C)C)NC(=O)C5=CC6=C(S5)C=CC(=C6)C(F)(F)P(O)(O)=O)=O)C7=CC=C(C=C7)C=8SC=CN8)=O)C)=O)=O
PubChem CID	166594150

数据库链接

PubChem CID	166594150

关联配体

Ligand ID	12409
名称	AK-2292
别名	AK2292
类别	Synthetic organic
学名	[[2-[[(2S)-1-[(2S)-2-[[3-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pent-4-ynyl-methylamino]-3-oxopropyl]-[4-(1,3-thiazol-2-yl)phenyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid
生物活性评价	The DC₅₀ for AK-2292-mediated degradation of total STAT5 protein is 100 nM . AK-2292 induces degradation of STAT5 protein in human AML and ALL cell lines, and produces an antitumour effect in CML xenograft models.
评价	AK-2292 is a PROTAC that mediates degradation of the STAT5A/B transcription factors . It contains a STAT5-binding ligand (AK-305; PubChem CID 166594169) linked to lenalidomide moeity that mediates cereblon binding, and directs the STAT5 proteins for ubiquitination and proteosomal degradation. AK-2292 was designed to evaluate STAT5 degradation as a therapeutic strategy for haematologic malignancies such as acute myeloid leukemia (AML). The PROTAC selectively inhibits phosphorylation and transcriptional activity of STAT5 in vitro and in vivo.
配体家族	PROTACs, molecular glues and other degraders

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参考文献

1. Kaneshige A, Bai L, Wang M, McEachern D, Meagher JL, Xu R, Kirchhoff PD, Wen B, Sun D, Stuckey JA et al.. (2023) Discovery of a Potent and Selective STAT5 PROTAC Degrader with Strong Antitumor Activity In Vivo in Acute Myeloid Leukemia.. J Med Chem, 66 (4): (2717-2743). [PMID:36735833]

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