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cis mz1  (MedChemExpress)


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    MedChemExpress cis mz1
    HIV latency reversal in ART-suppressed donors by bivalent degraders of the BET proteins. ( A ) BET inhibitor JQ1 is highlighted in gray. Degraders <t>MZ1</t> and ZXH-3-26 use JQ1 linked to either Von Hippel-Lindau (VHL) (green) or CRBN (orange) recruiting ligands. ( B ) A targeted dose titration of MZ1 and ZXH-3-26 in healthy, primary CD4+ T-cells ( n = 1 donor) identifies BRD4-specific degradation at 10 nM and 5 nM, respectively. Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the dimethyl sulfoxide (DMSO) control. ( C ) Total CD4+ T-cells from ART-suppressed donors were treated for 24 hours with MZ1 alone ( n = 4, SD) or in combination with I nhibitor of Ap optosis inhibitor (IAPi) AZD5582 ( n = 3, SD) and induction of gag cell-associated RNA assayed by quantitative real-time PCR. Four to five replicates of 1–2E6 cells per donor per condition were assayed. Each dot represents the average of these replicates per unique donor. Phorbol 12-myristate 13-acetate (PMA)/Ionomycin results are graphed independently due to differences in normalization (see Materials and Methods). Significance was assessed relative to DMSO control by Kruskal-Wallis with uncorrected Dunn’s multiple comparison test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001, (****) P < 0.0001. ( D ) BET protein levels as assayed by western blot in the 4 ART-suppressed donors ( n = 4, SD). Cells were treated concurrently with those for RNA isolation. BET protein levels are quantitated relative to GAPDH levels for all donors. cisMZ1 could not be assayed in all donors due to cell limitations ( n = 2, range).
    Cis Mz1, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 94/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Images

    1) Product Images from "BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells"

    Article Title: BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells

    Journal: Journal of Virology

    doi: 10.1128/jvi.01777-24

    HIV latency reversal in ART-suppressed donors by bivalent degraders of the BET proteins. ( A ) BET inhibitor JQ1 is highlighted in gray. Degraders MZ1 and ZXH-3-26 use JQ1 linked to either Von Hippel-Lindau (VHL) (green) or CRBN (orange) recruiting ligands. ( B ) A targeted dose titration of MZ1 and ZXH-3-26 in healthy, primary CD4+ T-cells ( n = 1 donor) identifies BRD4-specific degradation at 10 nM and 5 nM, respectively. Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the dimethyl sulfoxide (DMSO) control. ( C ) Total CD4+ T-cells from ART-suppressed donors were treated for 24 hours with MZ1 alone ( n = 4, SD) or in combination with I nhibitor of Ap optosis inhibitor (IAPi) AZD5582 ( n = 3, SD) and induction of gag cell-associated RNA assayed by quantitative real-time PCR. Four to five replicates of 1–2E6 cells per donor per condition were assayed. Each dot represents the average of these replicates per unique donor. Phorbol 12-myristate 13-acetate (PMA)/Ionomycin results are graphed independently due to differences in normalization (see Materials and Methods). Significance was assessed relative to DMSO control by Kruskal-Wallis with uncorrected Dunn’s multiple comparison test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001, (****) P < 0.0001. ( D ) BET protein levels as assayed by western blot in the 4 ART-suppressed donors ( n = 4, SD). Cells were treated concurrently with those for RNA isolation. BET protein levels are quantitated relative to GAPDH levels for all donors. cisMZ1 could not be assayed in all donors due to cell limitations ( n = 2, range).
    Figure Legend Snippet: HIV latency reversal in ART-suppressed donors by bivalent degraders of the BET proteins. ( A ) BET inhibitor JQ1 is highlighted in gray. Degraders MZ1 and ZXH-3-26 use JQ1 linked to either Von Hippel-Lindau (VHL) (green) or CRBN (orange) recruiting ligands. ( B ) A targeted dose titration of MZ1 and ZXH-3-26 in healthy, primary CD4+ T-cells ( n = 1 donor) identifies BRD4-specific degradation at 10 nM and 5 nM, respectively. Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the dimethyl sulfoxide (DMSO) control. ( C ) Total CD4+ T-cells from ART-suppressed donors were treated for 24 hours with MZ1 alone ( n = 4, SD) or in combination with I nhibitor of Ap optosis inhibitor (IAPi) AZD5582 ( n = 3, SD) and induction of gag cell-associated RNA assayed by quantitative real-time PCR. Four to five replicates of 1–2E6 cells per donor per condition were assayed. Each dot represents the average of these replicates per unique donor. Phorbol 12-myristate 13-acetate (PMA)/Ionomycin results are graphed independently due to differences in normalization (see Materials and Methods). Significance was assessed relative to DMSO control by Kruskal-Wallis with uncorrected Dunn’s multiple comparison test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001, (****) P < 0.0001. ( D ) BET protein levels as assayed by western blot in the 4 ART-suppressed donors ( n = 4, SD). Cells were treated concurrently with those for RNA isolation. BET protein levels are quantitated relative to GAPDH levels for all donors. cisMZ1 could not be assayed in all donors due to cell limitations ( n = 2, range).

    Techniques Used: Titration, Control, Expressing, Real-time Polymerase Chain Reaction, Comparison, Western Blot, Isolation

    Latency reversal and targeted degradation of BET degraders in a Jurkat-derived Latency Model. Latency reversal was assessed via the treatment of JLatA2 cells with a 16-point dose titration of ( A ) MZ1 and cis MZ1. JQ1(+) data is overlayed and provided in . Each titration was performed two independent times with biological triplicates ( n = 6, SEM) with GFP (open symbols) assessed by flow cytometry as a measure of latency reactivation and viability by live/dead stain (gray symbols). Error bars not extending past the symbol are not visible. The window of BRD4-specific degradation for MZ1 is highlighted in gray as determined by corresponding westerns for both BRD4L(ong) and BRD4S(hort) isoforms as well as BRD2 and BRD3 in JLatA2 cells ( B and C ). Matching experiments were performed for ( D ) ZXH-3-26 and the window of BRD4-selective degradation is highlighted in gray based on corresponding westerns ( E and F ). Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the DMSO control. Western blots are representative of at least two independent experiments (also see Fig. 4B; ).
    Figure Legend Snippet: Latency reversal and targeted degradation of BET degraders in a Jurkat-derived Latency Model. Latency reversal was assessed via the treatment of JLatA2 cells with a 16-point dose titration of ( A ) MZ1 and cis MZ1. JQ1(+) data is overlayed and provided in . Each titration was performed two independent times with biological triplicates ( n = 6, SEM) with GFP (open symbols) assessed by flow cytometry as a measure of latency reactivation and viability by live/dead stain (gray symbols). Error bars not extending past the symbol are not visible. The window of BRD4-specific degradation for MZ1 is highlighted in gray as determined by corresponding westerns for both BRD4L(ong) and BRD4S(hort) isoforms as well as BRD2 and BRD3 in JLatA2 cells ( B and C ). Matching experiments were performed for ( D ) ZXH-3-26 and the window of BRD4-selective degradation is highlighted in gray based on corresponding westerns ( E and F ). Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the DMSO control. Western blots are representative of at least two independent experiments (also see Fig. 4B; ).

    Techniques Used: Derivative Assay, Titration, Flow Cytometry, Staining, Control, Expressing, Western Blot

    Latency reversal and synergy with AZD5582 by degrader ZXH-3-26 is attenuated in a full-length Jurkat cell line. A 16-point dose titration of ( A ) ZXH-3-26 and JQ1 or ( B ) MZ1 and JQ1 in JLat10.6 cells. Each titration was performed two independent times with biological triplicates ( n = 6, SEM). Error bars not extending past the symbol are not visible. ( C ) 8-point dose titration of AZD-5582 and JQ1 in JLat10.6 cells. ( D ) 8-point dose titration of AZD-5582 and ZXH-3-26 in JLat10.6 cells. Data represents three independent experiments of each 8-point titration ( n = 3, SD). Bliss synergy calculations of ( E ) AZD5582/JQ1 and ( F ) AZD5582/ZXH-3-26 in JLat10.6 cells based on data in C/D ( n = 3, SD). Synergy experiments in JLatA2 cells are provided in .
    Figure Legend Snippet: Latency reversal and synergy with AZD5582 by degrader ZXH-3-26 is attenuated in a full-length Jurkat cell line. A 16-point dose titration of ( A ) ZXH-3-26 and JQ1 or ( B ) MZ1 and JQ1 in JLat10.6 cells. Each titration was performed two independent times with biological triplicates ( n = 6, SEM). Error bars not extending past the symbol are not visible. ( C ) 8-point dose titration of AZD-5582 and JQ1 in JLat10.6 cells. ( D ) 8-point dose titration of AZD-5582 and ZXH-3-26 in JLat10.6 cells. Data represents three independent experiments of each 8-point titration ( n = 3, SD). Bliss synergy calculations of ( E ) AZD5582/JQ1 and ( F ) AZD5582/ZXH-3-26 in JLat10.6 cells based on data in C/D ( n = 3, SD). Synergy experiments in JLatA2 cells are provided in .

    Techniques Used: Titration



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    Image Search Results


    HIV latency reversal in ART-suppressed donors by bivalent degraders of the BET proteins. ( A ) BET inhibitor JQ1 is highlighted in gray. Degraders MZ1 and ZXH-3-26 use JQ1 linked to either Von Hippel-Lindau (VHL) (green) or CRBN (orange) recruiting ligands. ( B ) A targeted dose titration of MZ1 and ZXH-3-26 in healthy, primary CD4+ T-cells ( n = 1 donor) identifies BRD4-specific degradation at 10 nM and 5 nM, respectively. Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the dimethyl sulfoxide (DMSO) control. ( C ) Total CD4+ T-cells from ART-suppressed donors were treated for 24 hours with MZ1 alone ( n = 4, SD) or in combination with I nhibitor of Ap optosis inhibitor (IAPi) AZD5582 ( n = 3, SD) and induction of gag cell-associated RNA assayed by quantitative real-time PCR. Four to five replicates of 1–2E6 cells per donor per condition were assayed. Each dot represents the average of these replicates per unique donor. Phorbol 12-myristate 13-acetate (PMA)/Ionomycin results are graphed independently due to differences in normalization (see Materials and Methods). Significance was assessed relative to DMSO control by Kruskal-Wallis with uncorrected Dunn’s multiple comparison test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001, (****) P < 0.0001. ( D ) BET protein levels as assayed by western blot in the 4 ART-suppressed donors ( n = 4, SD). Cells were treated concurrently with those for RNA isolation. BET protein levels are quantitated relative to GAPDH levels for all donors. cisMZ1 could not be assayed in all donors due to cell limitations ( n = 2, range).

    Journal: Journal of Virology

    Article Title: BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells

    doi: 10.1128/jvi.01777-24

    Figure Lengend Snippet: HIV latency reversal in ART-suppressed donors by bivalent degraders of the BET proteins. ( A ) BET inhibitor JQ1 is highlighted in gray. Degraders MZ1 and ZXH-3-26 use JQ1 linked to either Von Hippel-Lindau (VHL) (green) or CRBN (orange) recruiting ligands. ( B ) A targeted dose titration of MZ1 and ZXH-3-26 in healthy, primary CD4+ T-cells ( n = 1 donor) identifies BRD4-specific degradation at 10 nM and 5 nM, respectively. Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the dimethyl sulfoxide (DMSO) control. ( C ) Total CD4+ T-cells from ART-suppressed donors were treated for 24 hours with MZ1 alone ( n = 4, SD) or in combination with I nhibitor of Ap optosis inhibitor (IAPi) AZD5582 ( n = 3, SD) and induction of gag cell-associated RNA assayed by quantitative real-time PCR. Four to five replicates of 1–2E6 cells per donor per condition were assayed. Each dot represents the average of these replicates per unique donor. Phorbol 12-myristate 13-acetate (PMA)/Ionomycin results are graphed independently due to differences in normalization (see Materials and Methods). Significance was assessed relative to DMSO control by Kruskal-Wallis with uncorrected Dunn’s multiple comparison test, (*) P < 0.05, (**) P < 0.01, (***) P < 0.001, (****) P < 0.0001. ( D ) BET protein levels as assayed by western blot in the 4 ART-suppressed donors ( n = 4, SD). Cells were treated concurrently with those for RNA isolation. BET protein levels are quantitated relative to GAPDH levels for all donors. cisMZ1 could not be assayed in all donors due to cell limitations ( n = 2, range).

    Article Snippet: MZ1 (HY-107425, CAS: 1797406-69-9), cis MZ1 (HY-107425A, CAS: 1797406-72-4), and KL-2 (HY-123972, CAS: 900308-51-2) were purchased from MedChemExpress LLC.

    Techniques: Titration, Control, Expressing, Real-time Polymerase Chain Reaction, Comparison, Western Blot, Isolation

    Latency reversal and targeted degradation of BET degraders in a Jurkat-derived Latency Model. Latency reversal was assessed via the treatment of JLatA2 cells with a 16-point dose titration of ( A ) MZ1 and cis MZ1. JQ1(+) data is overlayed and provided in . Each titration was performed two independent times with biological triplicates ( n = 6, SEM) with GFP (open symbols) assessed by flow cytometry as a measure of latency reactivation and viability by live/dead stain (gray symbols). Error bars not extending past the symbol are not visible. The window of BRD4-specific degradation for MZ1 is highlighted in gray as determined by corresponding westerns for both BRD4L(ong) and BRD4S(hort) isoforms as well as BRD2 and BRD3 in JLatA2 cells ( B and C ). Matching experiments were performed for ( D ) ZXH-3-26 and the window of BRD4-selective degradation is highlighted in gray based on corresponding westerns ( E and F ). Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the DMSO control. Western blots are representative of at least two independent experiments (also see Fig. 4B; ).

    Journal: Journal of Virology

    Article Title: BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells

    doi: 10.1128/jvi.01777-24

    Figure Lengend Snippet: Latency reversal and targeted degradation of BET degraders in a Jurkat-derived Latency Model. Latency reversal was assessed via the treatment of JLatA2 cells with a 16-point dose titration of ( A ) MZ1 and cis MZ1. JQ1(+) data is overlayed and provided in . Each titration was performed two independent times with biological triplicates ( n = 6, SEM) with GFP (open symbols) assessed by flow cytometry as a measure of latency reactivation and viability by live/dead stain (gray symbols). Error bars not extending past the symbol are not visible. The window of BRD4-specific degradation for MZ1 is highlighted in gray as determined by corresponding westerns for both BRD4L(ong) and BRD4S(hort) isoforms as well as BRD2 and BRD3 in JLatA2 cells ( B and C ). Matching experiments were performed for ( D ) ZXH-3-26 and the window of BRD4-selective degradation is highlighted in gray based on corresponding westerns ( E and F ). Relative protein levels were determined by standardizing each protein to the GAPDH loading control, followed by expression relative to the DMSO control. Western blots are representative of at least two independent experiments (also see Fig. 4B; ).

    Article Snippet: MZ1 (HY-107425, CAS: 1797406-69-9), cis MZ1 (HY-107425A, CAS: 1797406-72-4), and KL-2 (HY-123972, CAS: 900308-51-2) were purchased from MedChemExpress LLC.

    Techniques: Derivative Assay, Titration, Flow Cytometry, Staining, Control, Expressing, Western Blot

    Latency reversal and synergy with AZD5582 by degrader ZXH-3-26 is attenuated in a full-length Jurkat cell line. A 16-point dose titration of ( A ) ZXH-3-26 and JQ1 or ( B ) MZ1 and JQ1 in JLat10.6 cells. Each titration was performed two independent times with biological triplicates ( n = 6, SEM). Error bars not extending past the symbol are not visible. ( C ) 8-point dose titration of AZD-5582 and JQ1 in JLat10.6 cells. ( D ) 8-point dose titration of AZD-5582 and ZXH-3-26 in JLat10.6 cells. Data represents three independent experiments of each 8-point titration ( n = 3, SD). Bliss synergy calculations of ( E ) AZD5582/JQ1 and ( F ) AZD5582/ZXH-3-26 in JLat10.6 cells based on data in C/D ( n = 3, SD). Synergy experiments in JLatA2 cells are provided in .

    Journal: Journal of Virology

    Article Title: BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells

    doi: 10.1128/jvi.01777-24

    Figure Lengend Snippet: Latency reversal and synergy with AZD5582 by degrader ZXH-3-26 is attenuated in a full-length Jurkat cell line. A 16-point dose titration of ( A ) ZXH-3-26 and JQ1 or ( B ) MZ1 and JQ1 in JLat10.6 cells. Each titration was performed two independent times with biological triplicates ( n = 6, SEM). Error bars not extending past the symbol are not visible. ( C ) 8-point dose titration of AZD-5582 and JQ1 in JLat10.6 cells. ( D ) 8-point dose titration of AZD-5582 and ZXH-3-26 in JLat10.6 cells. Data represents three independent experiments of each 8-point titration ( n = 3, SD). Bliss synergy calculations of ( E ) AZD5582/JQ1 and ( F ) AZD5582/ZXH-3-26 in JLat10.6 cells based on data in C/D ( n = 3, SD). Synergy experiments in JLatA2 cells are provided in .

    Article Snippet: MZ1 (HY-107425, CAS: 1797406-69-9), cis MZ1 (HY-107425A, CAS: 1797406-72-4), and KL-2 (HY-123972, CAS: 900308-51-2) were purchased from MedChemExpress LLC.

    Techniques: Titration