AT 1

 CAS No.: 2098836-45-2  Cat No.: BP-400003  Purity: ≥98% 4.5  

AT 1 is a VHL-recruiting BRD4 degrader derived from a JQ1-based BET bromodomain ligand and designed as a selective PROTAC for BRD4. The BRD4-recognition portion binds bromodomain acetyl-lysine reader sites, with public sources emphasizing BRD4 selectivity, while the VHL ligand recruits the von Hippel-Lindau E3 ligase complex. In PROTAC design, AT 1 illustrates how a bromodomain inhibitor scaffold can be converted into a degradation-inducing molecule by attaching an E3-recruiting ligand through a linker that supports ternary-complex formation. Its principal function is to induce proximity between BRD4 and VHL, leading to ubiquitination and proteasome-dependent BRD4 depletion. AT 1 is useful for studying BET-family selectivity, BRD4-dependent transcriptional regulation, linker effects, and experimental differences between bromodomain inhibition and targeted removal of BRD4 protein.

AT 1

Structure of 2098836-45-2

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Category
PROTAC
Molecular Formula
C48H58ClN9O5S3
Molecular Weight
972.68
Appearance
White Solid

* For research and manufacturing use only. Not for human or clinical use.

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Purity
≥98%
Appearance
White Solid
ShelfLife
2 years
Storage
-20°C
Synonyms
BRD4 degrader AT1; (2S,4R)-1-((R)-2-acetamido-3-((6-(2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamido)hexyl)thio)-3-methylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
InChI Key
SQNZDYHMCMIGGV-TZPPCSJFSA-N
InChI
InChI=1S/C48H58ClN9O5S3/c1-27-29(3)66-47-40(27)41(33-16-18-35(49)19-17-33)54-37(44-56-55-30(4)58(44)47)23-39(61)50-20-10-8-9-11-21-65-48(6,7)43(53-31(5)59)46(63)57-25-36(60)22-38(57)45(62)51-24-32-12-14-34(15-13-32)42-28(2)52-26-64-42/h12-19,26,36-38,43,60H,8-11,20-25H2,1-7H3,(H,50,61)(H,51,62)(H,53,59)/t36-,37+,38+,43-/m1/s1
SMILES
CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NCCCCCCSC(C)(C)C(C(=O)N4CC(CC4C(=O)NCC5=CC=C(C=C5)C6=C(N=CS6)C)O)NC(=O)C)C7=CC=C(C=C7)Cl)C
Mechanism

Target: AT 1 selectively targets BRD4 with negligible degradation of BRD2 and BRD3.

Binding site: Its JQ1-derived ligand binds the acetyl-lysine pocket of BRD4 bromodomains.

Mechanism of action: AT 1 is a VHL-based BRD4 PROTAC rationally designed from ternary-complex structural information to enhance BRD4 selectivity relative to earlier BET degraders. The molecule links a (+)-JQ1-derived BET ligand to a von Hippel-Lindau ligand, enabling cooperative formation of a BRD4–AT 1–VHL ternary complex. This complex positions BRD4 for ubiquitination and proteasome-dependent degradation while sparing closely related BET proteins under reported conditions. AT 1 is useful for investigating BRD4-specific transcriptional functions, ternary-complex cooperativity, and structure-guided optimization of selective degraders.

Applications

• PROTAC-Mediated Oncogenic Protein Degradation: AT 1 is utilized to selectively degrade oncogenic proteins implicated in cancer progression. By harnessing the ubiquitin-proteasome system, AT 1 facilitates the targeted degradation of these proteins, offering a powerful approach to study cancer biology and elucidate potential therapeutic targets.

• Targeted Degradation in Neurodegenerative Research: AT 1 serves as a valuable tool in neurodegenerative disease research by enabling the degradation of proteins associated with neuronal damage. This application aids in understanding disease mechanisms and exploring new avenues for therapeutic intervention through selective protein elimination.

• PROTAC-Assisted Kinase Inhibition Studies: Employing AT 1 allows researchers to investigate kinase functions by degrading specific kinases of interest. This targeted approach provides insights into kinase signaling pathways and their roles in various cellular processes, enhancing the understanding of potential drug targets.

• Protein Homeostasis and Cellular Pathways: AT 1 is instrumental in studying protein homeostasis by degrading proteins involved in cellular pathways. This application sheds light on the dynamic regulation of protein levels and their impact on cellular function, contributing to the broader understanding of proteostasis.

1. Photoresponsive properties at (0 0 1), (1 1 1) and (1 1 0) LaAlO3/SrTiO3 interfaces
Hong Yan, Zhaoting Zhang, Ming Li, Shuanhu Wang, Lixia Ren, Kexin Jin J Phys Condens Matter. 2020 Mar 27;32(13):135002.doi: 10.1088/1361-648X/ab5ebf.
We report the photoresponsive characteristics of (0 0 1), (1 1 0), and (1 1 1) LaAlO3/SrTiO3 heterointerfaces deposited at different oxygen pressures using a 360 nm light. The results show that LaAlO3/SrTiO3 interfaces with less oxygen vacancies exhibit a larger resistance change when illuminated by light and a slower recovery process when light is off. In addition, the (1 1 0) LaAlO3/SrTiO3 heterointerfaces present the smallest photoinduced change and residual photoinduced change in the resistance, which are related to the negligible polarization discontinuity at the interfaces. Our results provide a deeper insight into the photoinduced properties in the 2D electron gas system, paving the way for the design of oxide optoelectronic devices.
2. Using 1,1,1-Trichloroethane degradation data to understand NAPL dissolution and solute transport at real sites
Valeureux D Illy, Gregory J V Cohen, Elicia Verardo, Patrick Höhener, Nathalie Guiserix, Olivier Atteia J Contam Hydrol. 2022 Feb;245:103934.doi: 10.1016/j.jconhyd.2021.103934.Epub 2021 Dec 6.
Analytical and numerical models describing the evolution of contaminant concentrations in the plume associated with the dissolution of NAPL source and degradation processes were presented in the literature. At real sites and particularly in complex aquifers like chalk, it is difficult to understand how the sources of contaminants evolve with time. 1,1,1-Trichloroethane (1,1,1-TCA) is one of the few compounds with a well-known hydrolysis constant, that can help to improve knowledge of the contaminant sources and transport rates of dissolved contaminants in groundwater by dating the spill. In this work, different scenarios that could explain the evolution of the concentrations of 1,1,1-TCA and its degradation product 1,1-Dichloroethene (1,1-DCE) at a real contaminated site were investigated by analytical and numerical modelling. The results show that (1) the peaks of concentration time series do not correspond to a single contamination event even in the case of a complex medium, (2) the multiphasic behavior of the concentration time series is dictated by the dissolution in a heterogeneous medium, and (3) the persistence of the concentrations can arise from a small residual organic phase or transport in dual domain medium.
3. (1Z,3Z)-1,4-diphenyl-1,4-bis(p-tolylmethylthio)-1,3-butadiene
F Freeman, H Lu, J W Ziller, E Rodriguez Acta Crystallogr C. 1995 Apr 15;51 ( Pt 4):659-61.doi: 10.1107/s0108270194007845.
The crystal structure of (1Z,3Z)-1,4-diphenyl-1,4-bis-(p-tolylmethylthio)-1,3-b utadiene (1), C32H30S2, is described. Compound (1) has an s-trans conformation. The single bond length, C(2)--C(2'), in compound (1) of 1.432 (5) A is shorter than the C(3)--C(4) single bond (1.48 A) in 1,3-butadiene and the double-bond length, C(1)--C(2), of 1.350 (3) A in compound (1) is comparable to that in 1,3-butadiene (1.34 A). The short C--C single and double bonds in (1) may be attributed to delocalization (resonance) over the planar four-atom unit, hybridization changes, the presence of the S atoms, and/or other factors.

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2

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Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
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