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Chemical Structure| 1797406-69-9 Chemical Structure| 1797406-69-9

Structure of MZ1
CAS No.: 1797406-69-9

Chemical Structure| 1797406-69-9

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MZ1 is a potent and selective PROTAC molecule capable of targeting BRD4 and the VHL E3 ubiquitin ligase, leading to the degradation of BRD4 protein. MZ1 has shown potential in the study of epigenetic diseases, such as cancer, by inducing BRD4 degradation.

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Product Details of MZ1

CAS No. :1797406-69-9
Formula : C49H60ClN9O8S2
M.W : 1002.64
SMILES Code : CC1=C(C)SC2=C1C(C3=CC=C(C=C3)Cl)=N[C@@H](CC(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N4[C@@H](C[C@H](C4)O)C(NCC5=CC=C(C6=C(N=CS6)C)C=C5)=O)=O)=O)=O)C7=NN=C(C)N27
MDL No. :N/A
InChI Key :PTAMRJLIOCHJMQ-PYNGZGNASA-N
Pubchem ID :122201421

Safety of MZ1

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of MZ1

epigenetics

Isoform Comparison

Biological Activity

Target
  • BET

    Brd3(BD2), Kd:13 nM

    Brd2(BD2), Kd:62 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
HeLa cells 1-3 µM 24 hours To test the selective degradation of Brd4 by MZ1 Nat Chem Biol. 2017 May;13(5):514-521.
MDA-MB-231 0.4 µM 12, 24, or 48 hours MZ1 efficiently downregulated the protein expression levels of BRD4 and BRD2. J Exp Clin Cancer Res. 2019 Aug 30;38(1):383.
MDA-MB-231R 0.4 µM 12, 24, or 48 hours MZ1 efficiently downregulated the protein expression levels of BRD4 and BRD2. J Exp Clin Cancer Res. 2019 Aug 30;38(1):383.
HeLa cells 0.1 µM 2 hours MZ1 treatment resulted in complete loss of BRD4 and a significant stabilization of MYC protein Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13457-13467.
LS174t cells 200 nM 2 hours MZ1 significantly reduced BRD4 signal intensity within 2 hours and caused clustering in the cytoplasm Neoplasia. 2019 Nov;21(11):1110-1120.
MM.1S cells 100 nM 24 hours MZ-1 inhibited BMSC- and IL-6-induced MYC mRNA and protein levels but did not affect JUNB expression. Blood Cancer J. 2024 Aug 19;14(1):138.
LS174t cells 1 µM 24 hours MZ1 induced complete degradation of BRD4 protein, followed by a reduction in MYC protein expression Neoplasia. 2019 Nov;21(11):1110-1120.
HeLa cells 25-125 nM 4 hours or 18 hours To evaluate the degradation effect of macroPROTAC-1 on Brd4, the results showed that macroPROTAC-1 could rapidly and effectively degrade Brd4. Angew Chem Int Ed Engl. 2020 Jan 20;59(4):1727-1734.
BT549 0.2, 0.4, 1 µM 48 or 96 hours MZ1 showed significant antiproliferative activity in BT549 cells. J Exp Clin Cancer Res. 2019 Aug 30;38(1):383.
SKOV3 0.2, 0.4, 1 µM 48 or 96 hours MZ1 showed significant antiproliferative activity in SKOV3 cells. J Exp Clin Cancer Res. 2019 Aug 30;38(1):383.
OVCAR3 0.2, 0.4, 1 µM 48 or 96 hours MZ1 showed significant antiproliferative activity in OVCAR3 cells. J Exp Clin Cancer Res. 2019 Aug 30;38(1):383.
SSM2c cells 125 nM 72 hours Combination of MZ1 and MRT-92 significantly inhibited melanoma cell growth and completely abrogated GLI1 expression. Oncogene. 2021 Jun;40(22):3799-3814.
A375 cells 250 nM 72 hours Combination of MZ1 and MRT-92 significantly inhibited melanoma cell growth and completely abrogated GLI1 expression. Oncogene. 2021 Jun;40(22):3799-3814.
MeWo cells 125 nM 72 hours Combination of MZ1 and MRT-92 significantly inhibited melanoma cell growth and completely abrogated GLI1 expression. Oncogene. 2021 Jun;40(22):3799-3814.
KYSE180 1 µM 8 hours After MZ1 treatment, BRDT protein was completely degraded, BRD4 expression was significantly decreased, and BRD2 and BRD3 protein levels were relatively unaffected. Cell Death Differ. 2021 Jul;28(7):2207-2220.
22RV1 cells 250 nM To evaluate the degradation effect of macroPROTAC-1 on Brd4 and its impact on Myc levels, the results showed that macroPROTAC-1 could significantly degrade Brd4 and reduce Myc levels. Angew Chem Int Ed Engl. 2020 Jan 20;59(4):1727-1734.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c nu/nu mice MDA-MB-231R xenograft model Intraperitoneal injection 10 mg/kg Once daily for two weeks MZ1 prevented the growth of JQ1-resistant tumors and reduced BRD4 expression levels. J Exp Clin Cancer Res. 2019 Aug 30;38(1):383.
Athymic Nude mice A375 melanoma xenograft model Intraperitoneal injection 100 mg/kg Once daily for 10 days Combination of MZ1 and MRT-92 significantly inhibited melanoma growth and completely abrogated GLI1 expression. Oncogene. 2021 Jun;40(22):3799-3814.
NOD scid gamma (NSG) mice Multiple myeloma xenograft model Intraperitoneal injection 5 mg/kg 5 times per week until tumors reached a maximum diameter of 1.5 cm MZ-1 alone or in combination with doxycycline significantly reduced tumor size and prolonged mouse survival. Blood Cancer J. 2024 Aug 19;14(1):138.
NOD scid gamma NSG™ mice Multiple myeloma xenograft model Intraperitoneal injection 5 mg/kg 5 times per week until tumors reached a maximum diameter of 1.5 cm MZ-1 significantly reduced tumor size and prolonged mouse survival, and its combination with doxycycline further enhanced the anti-tumor effect. Blood Cancer J. 2024 Aug 19;14(1):138.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.00mL

0.20mL

0.10mL

4.99mL

1.00mL

0.50mL

9.97mL

1.99mL

1.00mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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