MZ1 | BRD4 remover | CAS#1797406-69-9

MedKoo Cat#: 525698 | Name: MZ1

Description:

WARNING: This product is for research use only, not for human or veterinary use.

MZ1 is a potent inducer of reversible, long-lasting and selective removal of BRD4 over BRD2 and BRD3.

Chemical Structure

MZ1

CAS#1797406-69-9

Theoretical Analysis

MedKoo Cat#: 525698

Name: MZ1

CAS#: 1797406-69-9

Chemical Formula: C49H60ClN9O8S2

Exact Mass: 1001.3695

Molecular Weight: 1002.64

Elemental Analysis: C, 58.70; H, 6.03; Cl, 3.54; N, 12.57; O, 12.77; S, 6.40

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 1,950.00	Ready to ship
500mg	USD 3,450.00	Ready to Ship
1g	USD 4,950.00	2 Weeks

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Synonym

MZ1; MZ-1; MZ 1; MZ 1 (PROTAC)

IUPAC/Chemical Name

(4R)-N-[14-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-1,13-dioxo-3,6,9-trioxa-12-azatetradec-1-yl]-3-methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-L-prolinamide

InChi Key

PTAMRJLIOCHJMQ-PYNGZGNASA-N

InChi Code

InChI=1S/C49H60ClN9O8S2/c1-28-30(3)69-48-41(28)42(33-12-14-35(50)15-13-33)54-37(45-57-56-31(4)59(45)48)23-39(61)51-16-17-65-18-19-66-20-21-67-26-40(62)55-44(49(5,6)7)47(64)58-25-36(60)22-38(58)46(63)52-24-32-8-10-34(11-9-32)43-29(2)53-27-68-43/h8-15,27,36-38,44,60H,16-26H2,1-7H3,(H,51,61)(H,52,63)(H,55,62)/t36-,37+,38+,44-/m1/s1

SMILES Code

O=C(NCC1=CC=C(C2=C(C)N=CS2)C=C1)[C@H]3N(C([C@H](C(C)(C)C)NC(COCCOCCOCCNC(C[C@H]4C5=NN=C(C)N5C6=C(C(C)=C(C)S6)C(C7=CC=C(Cl)C=C7)=N4)=O)=O)=O)C[C@H](O)C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R04B30

QC Data

View QC data: current batch, Lot#C20R04B30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

MZ 1 is a PROTAC BRD4 degrader.

In vitro activity:

All three PROTAC compounds demonstrated complete removal of BRD4 with no detectable protein observed after 24 h of treatment. In contrast, removal of BRD2 and BRD3 was not complete after 24 h. MZ1 exhibited the highest efficacy among the three compounds. MZ2, which is structurally analogous to MZ1 except for a longer linker containing four PEG units, showed a weaker removal effect compared to MZ1. MZ3, containing an additional phenylalanine moiety between the linker and the VHL ligand, showed to be the least effective at removing BRD2 and BRD3. Together, the data demonstrate potent and effective degradation of BET proteins and suggested a preferential degradation effect on BRD4 over BRD2 and BRD3. The latter observation was unexpected given the parental compound JQ1 is a pan-BET inhibitor and our PROTACs bind with similar affinities to BET bromodomains. Reference: ACS Chem Biol. 2015 Aug 21; 10(8): 1770–1777. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548256/

In vivo activity:

Necropsy revealed a similar tumor distribution for all mice implanted with A2780 cells (Fig. 2B), including an extensive tumor mass beneath the liver and omentum as well as small tumor nodules scattered in pelvic areas, on abdominal walls, intestines, and diaphragm. However, noticeably less tumor foci were observed in these areas of mice treated with MZ-1 compared with those treated with control antibody. In addition, at the end of the experiment, ascites were present in 4 of 9 control mice, although they were absent from all the 9 MZ-1–treated mice (Table 2). Compared with control antibody, MZ-1 treatment significantly reduced tumor burden and nodule number by 51% (P = 0.01) and 58% (P = 0.0002), respectively, suggesting an efficient inhibitory effect of MZ-1 on A2780 i.p. tumor growth. This study further examined the periostin expression in A2780 i.p. xenografts by Western blot. periostin levels were much lower in xenografts treated with MZ-1 in comparison with those treated with control antibody (Supplementary Fig. S2). No side effects or severe toxicity of MZ-1 treatment were observed during the whole course of treatment. Reference: Mol Cancer Ther. 2011 Aug;10(8):1500-8. https://mct.aacrjournals.org/content/10/8/1500.long

	Solvent	mg/mL	mM
Solubility
	Soluble in DMSO	30.0	29.90

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 1,002.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zengerle M, Chan KH, Ciulli A. Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4. ACS Chem Biol. 2015 Aug 21;10(8):1770-7. doi: 10.1021/acschembio.5b00216. Epub 2015 Jun 16. PMID: 26035625; PMCID: PMC4548256. 2. Zhu M, Saxton RE, Ramos L, Chang DD, Karlan BY, Gasson JC, Slamon DJ. Neutralizing monoclonal antibody to periostin inhibits ovarian tumor growth and metastasis. Mol Cancer Ther. 2011 Aug;10(8):1500-8. doi: 10.1158/1535-7163.MCT-11-0046. Epub 2011 Jun 13. PMID: 21670235.

In vitro protocol:

In vivo protocol:

1. Zhu M, Saxton RE, Ramos L, Chang DD, Karlan BY, Gasson JC, Slamon DJ. Neutralizing monoclonal antibody to periostin inhibits ovarian tumor growth and metastasis. Mol Cancer Ther. 2011 Aug;10(8):1500-8. doi: 10.1158/1535-7163.MCT-11-0046. Epub 2011 Jun 13. PMID: 21670235.

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