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Merck
CN

SML3180

PZ15227

≥98% (HPLC), senolytic agent targeting BCL-XL protein, powder

别名:

4-[4-[[2-(4-Chlorophenyl)-5,5-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-[4-[4-[4-[[2-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]ethoxy]methyl]-1H-1,2,3-triazol-1-yl]-1-oxobutyl]-1-piperazinyl]-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]phenyl]sulfonyl]benzamide, PZ 15227

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关于此项目

经验公式（希尔记法）:
C71H82ClF3N12O12S3
化学文摘社编号:
2143464-25-7
分子量:
1484.13
UNSPSC代码:
12352200
NACRES:
NA.21

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产品名称

PZ15227, ≥98% (HPLC)

质量水平

100

方案

≥98% (HPLC)

表单

powder

颜色

white to beige

溶解性

DMSO: 2 mg/mL, clear

储存温度

2-8°C

SMILES字符串

CC1(C)CCC(C2=CC=C(Cl)C=C2)=C(CN3CCN(C4=CC=C(C(NS(C5=CC=C(N[C@@H](CSC6=CC=CC=C6)CCN7CCN(C(CCCN8C=C(COCCOCCNC9=C%10C(C(N(C%11CCC(NC%11=O)=O)C%10=O)=O)=CC=C9)N=N8)=O)CC7)C(S(C(F)(F)F)(=O)=O)=C5)(=O)=O)=O)C=C4)CC3)C1

InChI

1S/C71H82ClF3N12O12S3/c1-70(2)27-25-57(48-13-17-51(72)18-14-48)50(43-70)44-83-33-35-84(36-34-83)54-19-15-49(16-20-54)66(90)80-102(96,97)56-21-22-59(62(42-56)101(94,95)71(73,74)75)77-52(47-100-55-8-4-3-5-9-55)26-30-82-31-37-85(38-32-82)64(89)12-7-29-86-45-

InChI key

OWEARFNXBBNNKR-ADXOFTSBSA-N

相关类别

一般描述

PZ15227 is a proteolysis targeting chimeras (PROTACs) based senolytic agent targeting BCL-XL protein. It is a derivative of ABT-263, a Bcl-2 family protein inhibitor. PZ15227 degrades Bcl-xl by recruiting celebron (CRBN) E3 ligase in senescent cells but not in platelets. Comparative to its parent compound, PZ15227 is less toxic to human platelets because of low CRBN expression in platelets.

生化/生理作用

Bcl-xl specific PROTAC that potently targets Bcl-xl for degradation by cereblon E3 ligase

储存分类代码

11 - Combustible Solids

WGK

WGK 3

闪点(°F)

Not applicable

闪点(°C)

Not applicable

法规信息

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分析证书(COA)

Lot/Batch Number
0000176058
0000176059
0000176059
0000176058

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PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors
Zhang P, et al.
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Ryan Kolb et al.
Nature communications, 12(1), 1281-1281 (2021-02-26)
Regulatory T cells (Tregs) play an important role in maintaining immune homeostasis and, within tumors, their upregulation is common and promotes an immunosuppressive microenvironment. Therapeutic strategies that can eliminate Tregs in the tumor (i.e., therapies that do not run the
Ha-Neui Kim et al.
JCI insight, 5(19) (2020-09-02)
In aging mice, osteoclast number increases in cortical bone but declines in trabecular bone, suggesting that different mechanisms underlie age-associated bone loss in these 2 compartments. Osteocytes produce the osteoclastogenic cytokine RANKL, encoded by Tnfsf11. Tnfsf11 mRNA increases in cortical
Yonghan He et al.
Nature communications, 11(1), 1996-1996 (2020-04-26)
Small molecules that selectively kill senescent cells (SCs), termed senolytics, have the potential to prevent and treat various age-related diseases and extend healthspan. The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity.

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