Name: TD-165
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Storage

Store at -20°C, protect from light

IUPACName

(2S,4R)-1-[(2S)-2-[11-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]undecanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

(2S,4R)-1-((2S)-2-(11-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)undecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

Boiling Point

1096.3±65.0°C at 760 Torr

Density

1.292±0.06 g/cm3

InChI Key

KSXVXTSIDVRZBR-IINAPWRYSA-N

InChI

InChI=1S/C46H59N7O8S/c1-28-39(62-27-49-28)30-19-17-29(18-20-30)25-48-41(57)35-24-31(54)26-52(35)45(61)40(46(2,3)4)50-36(55)16-11-9-7-5-6-8-10-12-23-47-33-15-13-14-32-38(33)44(60)53(43(32)59)34-21-22-37(56)51-42(34)58/h13-15,17-20,27,31,34-35,40,47,54H,5-12,16,21-26H2,1-4H3,(H,48,57)(H,50,55)(H,51,56,58)/t31-,34?,35+,40-/m1/s1

SMILES

O=C1NC(=O)C(N2C(=O)C=3C=CC=C(NCCCCCCCCCCC(=O)NC(C(=O)N4CC(O)CC4C(=O)NCC=5C=CC(=CC5)C=6SC=NC6C)C(C)(C)C)C3C2=O)CC1

Mechanism

Target: TD-165 targets cereblon by recruiting VHL-mediated ubiquitination machinery.

Binding site: Its cereblon ligand binds the IMiD pocket of the CRBN substrate receptor.

Mechanism of action: TD-165 is a PROTAC-based cereblon degrader that combines a CRBN-binding ligand, linker, and von Hippel-Lindau ligand. This architecture is designed to recruit CRBN into proximity with the VHL E3 ligase complex, enabling ubiquitination and degradation of cereblon itself. As an E3-directed degrader, TD-165 is useful for investigating CRBN abundance, IMiD-dependent biology, E3 ligase crosstalk, and the consequences of depleting an E3 substrate receptor. It can also support control studies evaluating how CRBN loss affects degradation activity of cereblon-recruiting PROTACs.

Applications

• Protac-Enabled Cancer Research: TD-165 facilitates the targeted degradation of oncogenic proteins, offering a powerful tool for cancer researchers aiming to elucidate the roles of specific proteins in tumor progression. By selectively degrading proteins involved in cancer pathways, it aids in identifying potential therapeutic targets and understanding disease mechanisms.

• Neurodegeneration Studies with Protac: This product is instrumental in neuroscience research focused on neurodegenerative diseases. By enabling the degradation of proteins implicated in neuronal damage, TD-165 assists in the study of disease pathogenesis and the development of novel therapeutic strategies aimed at preventing or slowing neuronal loss.

• Drug Resistance Investigations via Targeted Degradation: TD-165 is valuable for exploring mechanisms of drug resistance in various diseases. By degrading resistance-conferring proteins, researchers can better understand how these proteins contribute to resistance and identify new approaches to overcome it, enhancing the efficacy of existing treatments.

• Signaling Pathway Analysis Using Protac: Researchers can employ TD-165 to dissect complex signaling networks by degrading key signaling proteins. This approach allows for the investigation of protein function and interaction within pathways, providing insights into cellular processes and potential intervention points for therapeutic development.

1. Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera.

Kim, K., Lee, D.H., Park, S., Jo, S.H., Ku, B., Park, S.G., Park, B.C., Jeon, Y.U., Ahn, S., Kang, C.H. and Hwang, D., 2019. Scientific reports, 9(1), pp.1-14.

Proteolysis targeting chimeras (PROTACs) are an emerging strategy for promoting targeted protein degradation by inducing the proximity between targeted proteins and E3 ubiquitin ligases. Although successful degradation of numerous proteins by PROTACs has been demonstrated, the elements that determine the degradability of PROTAC-targeted proteins have not yet been explored. In this study, we developed von Hippel-Lindau-Cereblon (VHL-CRBN) heterodimerizing PROTACs that induce the degradation of CRBN, but not VHL. A quantitative proteomic analysis further revealed that VHL-CRBN heterodimerizing PROTACs induced the degradation of CRBN, but not the well-known immunomodulatory drug (IMiD) neo-substrates, IKAROS family zinc finger 1 (IKZF1) and -3 (IZKF3). Moreover, truncation of disordered regions of CRBN and the androgen receptor (AR) attenuated their PROTAC-induced degradation, and attachment of the disordered region to stable CRBN or AR facilitated PROTAC-induced degradation. Thus, these results suggest that the intrinsically disordered region of targeted proteins is essential for efficient proteolysis, providing a novel criterion for choosing degradable protein targets.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂