SML4304

SIM1

Name: SIM1
Brand: SIGMA

≥98% (HPLC), powder, BET degrader

别名:

(S)-N,N′-(11-((2-((S)-1-((2S,4R)-4-Hydroxy-2-(4-(4-methylthiazol-5-yl)benzylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylamino)-2-oxoethoxy)methyl)-11-methyl-3,6,9,13,16,19-hexaoxahenicosane-1,21-diyl)bis(2-((6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide)

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关于此项目

经验公式（希尔记法）:

C₇₉H₉₈Cl₂N₁₄O₁₃S₃

化学文摘社编号:

2719051-84-8

分子量:

1618.81

UNSPSC Code:

12352200

Assay:

≥98% (HPLC)

Form:

powder

Quality level:

100

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技术服务

需要帮助？我们经验丰富的科学家团队随时乐意为您服务。

让我们为您提供帮助

Quality Level

100

assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

-10 to -25°C

Application

SIM1 is suitable for use to study intracellular degradation of BET proteins, and to produce a trivalent PROTAC with enhanced target degradation.

Biochem/physiol Actions

SIM1, a PROTAC degrader, is a highly potent bromo and extra terminal (BET) protein degrader (BRD2/3/4 Dmax50 = 57.3/413.9/96.3 pM post 22h using HEK293 expressing respective BRD; BRD2/3/4 λmax/h = 2.8/1.2/1.9 nM) that corresponds to a trivalent chimera composed of a Von Hippel Lindau (VHL) E3 ligase-targeting ligand linked to two molecules of BET inhibitor (+)-(S)-JQ1. Compared to bivalent degraders, SIM1 shows higher and more sustained degradation efficacy by simultaneously engaging two BET bromodomains with high avidity in a cis intramolecular fashion, exhibiting positive cooperativity, leading to more potent anticancer activity (MV4;11 AML viability IC50 = 1.1 nM/SIM1 vs 11.3 nM/MZ1 post 48h treatment). SIM1 is found to interact with the BD2 and BD1 bromodomains of BRD4, creating a ternary complex with VHL and BRD4. This interaction increases target binding valency and extends the duration of specific molecular interactions with the target.