PAC

Research use only, not for human use.

PAC1 (Compound PAC1) is a novel PROTAC antibody conjugate, more potent estrogen receptor-alpha (ERα) degrader compared to PROTAC without antibody conjugation.

PAC1 (Compound PAC1) is a novel PROTAC antibody conjugate, more potent estrogen receptor-alpha (ERα) degrader compared to PROTAC without antibody conjugation.

Treatment of HER2 expressing cells with HER2 antibody containing PAC Anti-HER2(Endox-XIAP) results in a marked decreased Estrogen Receptor-alpha (ERα) levels with an IC50 of 132 ng/mL. The PROTAC-Antibody Conjugate (PAC) molecules comprise an antibody conjugated via a linker (L1) to a PROTAC, wherein the PROTAC comprises an ubiquitin E3 ligase binding group (“E3LB”), a linker (“L2”) and a protein binding group (“PB”). The following sections describe the components that comprise the PAC. To obtain a PAC having potent efficacy and a desirable therapeutic index, the following components are provided. 1. Antibody (Ab): The antibody portion of a PAC can target a cell that expresses an antigen whereby the antigen specific PAC is delivered intracellularly to the target cell, typically through endocytosis While PACs that comprise an antibody directed to an antigen that is not found on the cell surface may result in less specific intracellular delivery of the PROTAC portion into the cell, the PAC may still undergo pinocytosis. 2. Linkers (L1): A“linker” (L1) is a bifunctional or multifunctional moiety that can be used to link one or more PROTAC moieties (D) to an antibody (Ab) to form a PAC. In some embodiments, PACs can be prepared using a L1 having reactive functionalities for covalently attaching to the PROTAC and to the antibody. 3. PROTAC(D) .

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Compound PAC1

PROTACs

PROTAC

PROTAC

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2158322-33-7

1674.93

C94H107N13O16

>98% (HPLC)

In Vitro:?DMSO : 70 mg/mL (41.79 mM)

CCC(=C(C1=CC=C(C=C1)OCCN(C)C(=O)COCCOCCNC(=O)C2=CC=C(C=C2)C(=O)N3C(C(C(=O)N(C4=C3C=C(C=C4)C#N)CC5=C(C=CC6=CC=CC=C65)OC)NC(=O)C(C)NC)C)C7=CC=C(C=C7)OCC8=CC=C(C=C8)NC(=O)C(CCCNC(=O)N)NC(=O)C(C(C)C)NC(=O)CCCCCN9C(=O)C=CC9=O)C1=CC=CC=C1

4-((2S,3S)-8-Cyano-5-((2-methoxynaphthalen-1-yl)methyl)-2-methyl-3-((S)-2-(methylamino)propanamido)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-1-carbonyl)-N-(2-(2-(2-((2-(4-((Z)-1-(4-((4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexan

(-20℃)

With Ice Pack

≥ 2 years