| Size | Price | |
|---|---|---|
| 1mg | ||
| 5mg | ||
| Other Sizes |
| Targets |
BRD4 BD1/BD2
|
|---|---|
| References | |
| Additional Infomation |
The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 are key regulators of transcription, epigenetics, and cancer, and serve as the targets of the pan-BET selective bromodomain inhibitor JQ1. However, the lack of selectivity among BET family members limits the utility of current inhibitors for target validation and may lead to off-target effects or toxicity in therapeutic applications. To address this, we designed Proteolysis-Targeting Chimeras (PROTACs) that link JQ1 to a ligand for the E3 ubiquitin ligase VHL, aiming to induce targeted degradation of BET proteins. One such compound, MZ1, potently and rapidly induces reversible, long-lasting, and unexpectedly selective degradation of BRD4 over BRD2 and BRD3. This activity is dependent on VHL binding and occurs at concentrations low enough to avoid stabilization of HIF-1α. Analysis of gene expression profiles of cancer-related genes responsive to JQ1 reveals that MZ1 induces a distinct and more restricted transcriptional response, consistent with selective suppression of BRD4. These findings open new avenues for exploring the cellular functions and therapeutic potential of selective BRD4 targeting.[1]
|
| Molecular Formula |
C49H60CLN9O8S2
|
|---|---|
| Molecular Weight |
1002.64
|
| Exact Mass |
1001.369
|
| Elemental Analysis |
C, 58.70; H, 6.03; Cl, 3.54; N, 12.57; O, 12.77; S, 6.40
|
| CAS # |
1797406-72-4
|
| Related CAS # |
MZ 1;1797406-69-9
|
| PubChem CID |
124201820
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
5
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
21
|
| Heavy Atom Count |
69
|
| Complexity |
1750
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)NCCOCCOCCOCC(=O)N[C@H](C(=O)N4C[C@H](C[C@H]4C(=O)NCC5=CC=C(C=C5)C6=C(N=CS6)C)O)C(C)(C)C)C7=CC=C(C=C7)Cl)C
|
| InChi Key |
PTAMRJLIOCHJMQ-HADAFJFFSA-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+/m0/s1
|
| Chemical Name |
(2S,4S)-1-[(2S)-2-[[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
|
| Synonyms |
1797406-72-4; L-Prolinamide, 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]-, (4S)-; L-Prolinamide, 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)-, (4S)-; RefChem:350884; cis-MZ 1;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9974 mL | 4.9868 mL | 9.9737 mL | |
| 5 mM | 0.1995 mL | 0.9974 mL | 1.9947 mL | |
| 10 mM | 0.0997 mL | 0.4987 mL | 0.9974 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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