{"id":118,"date":"2023-10-27T13:03:19","date_gmt":"2023-10-27T12:03:19","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?page_id=118"},"modified":"2026-01-26T14:11:16","modified_gmt":"2026-01-26T14:11:16","slug":"mzp-54","status":"publish","type":"page","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/research\/chemical-probes\/mzp-54\/","title":{"rendered":"MZP-54"},"content":{"rendered":"
\n
\"BET
\n <\/source><\/source><\/figure>\n

MZP-54<\/p>\n

Protein Target(s) Name<\/strong>: BET proteins BRD4, BRD3, BRD2<\/p>\n

Mechanism of Action<\/strong>: PROTAC degrader<\/p>\n

Description<\/strong>: VH032 (VHL) based and IBET-726 based PROTAC that degrades BET proteins in cells. MZP-54 exhibits preferential degradation of BRD3 and BRD4 at nM concentrations over BRD2 (1<\/em>).<\/p>\n

Chemical Name<\/strong>: (2S<\/em>,4R<\/em>)-1-((S<\/em>)-1-(4-((2S<\/em>,4R<\/em>)-1-acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)-15-(tert<\/em>-butyl)-1,13-dioxo-5,8,11-trioxa-2,14-diazahexadecan-16-oyl)-4-hydroxy-N<\/em>-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide<\/p>\n

CAS Number<\/strong>: 2010159-47-2<\/p>\n

In vitro pharmacology*:<\/strong>\u00a0MZP-54 reduces BET protein levels in human cells: Brd4 pDC50 | Dmax (%) in HeLa cells (24 h) = 8.1 | 98; Brd3 pDC50 | Dmax (%) in HeLa cells (24 h) = 7.3 | 91
\nMZP-54 shows antiproliferative and Myc-suppression activity in AML MV4;11 and HL60 cells: pEC50 in MV4;11 | HL-60 cells (48 h) = 7.3 | 6.6
\nData from ref. (1<\/em>)<\/p>\n

*DC50: concentration in molar causing 50% reduction of protein level relative to vehicle control treatment.
\nDmax: maximum reduction of protein level relative to vehicle control treatment.
\nEC50: effective concentration in molar causing 50% reduction of cell viability relative to vehicle control treatment.<\/p>\n

Biophysical binding data<\/strong>: Binary Kd (Brd4-BD2) = 4 nM;\u00a0Binary Kd (VHL) = 105 nM; Ternary Kd (VHL, in the presence of Brd4-BD2) = 230 nM; cooperativity (alpha) = 0.5
\nData from ref. (1<\/em>)<\/p>\n

In vivo PK data<\/strong>: not available<\/p>\n

Crystal Structure<\/strong>: not available<\/p>\n

Negative control<\/strong>: not available<\/p>\n

<\/div>\n

Primary References:\u00a0<\/strong><\/p>\n

    \n
  1. Chan et al. (2018<\/strong>)\u00a0Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived From Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds.\u00a0J. Med. Chem.<\/em>\u00a061<\/em>, 504.\u00a0 DOI:\u00a010.1021\/acs.jmedchem.6b01912<\/a>; PMID:\u00a028595007<\/a><\/li>\n<\/ol>\n

    \u00a0<\/p>\n

    Articles that have used MZP-54<\/strong>:<\/p>\n

      \n
    1. 2018 Chan J Med Chem\u00a0http:\/\/dx.doi.org\/10.1021\/acs.jmedchem.6b01912<\/a><\/li>\n
    2. 2021 Castro RSC Med Chem\u00a0https:\/\/doi.org\/10.1039\/D1MD00215E<\/a><\/li>\n
    3. 2021 Weng J Med Chem\u00a0https:\/\/doi.org\/10.1021\/acs.jmedchem.1c01576<\/a><\/li>\n
    4. 2022 Garc\u00eda Jim\u00e9nez J Med Chem\u00a0https:\/\/doi.org\/10.1021\/acs.jmedchem.2c00201<\/a><\/li>\n<\/ol>\n

      More information<\/h2>\n

      More information on our chemical probes can be found from the\u00a0Chemical Probes portal<\/a>, and from commercial vendors such as\u00a0Tocris Bio-Techne<\/a>.<\/p>\n

      Related Links<\/h3>\n