| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
VHL
The primary molecular target of ZXH-4-130 TFA is cereblon (CRBN), an E3 ubiquitin ligase substrate receptor. As a hetero-PROTAC, it functions as a CRBN-VHL compound, meaning it simultaneously engages CRBN and the von Hippel-Lindau (VHL) E3 ligase complex. This bifunctional design leads to the selective ubiquitination and proteasomal degradation of CRBN itself, making it a degrader of the E3 ligase component rather than a typical PROTAC that targets a separate protein of interest. |
|---|---|
| ln Vitro |
ZXH-4-130 TFA (100 nM; pretreatment for 2 hours; subsequent treatment with 1 μM pomalidomide for 96 hours) has a statistically significant preventative effect [1] that greatly inhibits the cytotoxicity of pomalidomide (1 μM). In MM1.S cells, ZXH-4-130 TFA (50 nM pretreatment) prevents GSPT1 degradation caused by CC-885 [1]. ZXH-4-130 (100 nM) TFA causes nearly total CRBN degradation, but only partially blocks THAL-SNS-032's activity on CDK9 [1]. This is followed by a 6-hour THAL-SNS-032 treatment.
In vitro studies have demonstrated that ZXH-4-130 TFA is a highly efficient and selective degrader of CRBN. At a concentration of 10 nM in MM1.S cells, ZXH-4-130 TFA induces approximately 80% degradation of CRBN. At 100 nM with a 2-hour pre-treatment, it significantly inhibits the cytotoxic effects of 1 μM pomalidomide. Additionally, a 50 nM pre-treatment effectively reverses GSPT1 degradation induced by CC-885 in MM1.S cells. At 100 nM with a 2-hour pre-treatment, it almost completely promotes CRBN degradation. |
| ln Vivo |
In vivo activity data for ZXH-4-130 TFA as a standalone compound are not extensively reported in the available literature. As a PROTAC molecule, its in vivo efficacy would depend on its pharmacokinetic properties and the specific disease model being studied. It is primarily used as a research tool to study the role of CRBN in the ubiquitin-proteasome system. Further studies are needed to evaluate its in vivo pharmacokinetic and pharmacodynamic properties.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for ZXH-4-130 TFA typically involve studying its interaction with CRBN and the VHL E3 ligase complex. Surface plasmon resonance (SPR) or fluorescence polarization techniques can be used to measure the binding affinity of the compound for CRBN. Ternary complex formation assays can be performed to evaluate the ability of the compound to simultaneously engage CRBN and the VHL E3 ligase. Cellular degradation assays are used to assess the potency of CRBN degradation.
|
| Cell Assay |
In vitro cell-based assays for ZXH-4-130 TFA typically involve treatment of cultured cells with the compound followed by assessment of CRBN degradation. Cells such as MM1.S are treated with ZXH-4-130 TFA, and CRBN levels are measured by Western blotting or immunofluorescence to assess degradation efficiency. Dose-response experiments are performed to determine the DC50 (half-maximal degradation concentration). Functional assays may be performed to assess the consequences of CRBN degradation on downstream signaling pathways.
|
| Animal Protocol |
In vivo animal studies for ZXH-4-130 TFA are not extensively reported. As a PROTAC molecule, it could potentially be used in mouse xenograft models to assess its ability to degrade CRBN and modulate the ubiquitin-proteasome system. Typical protocols would involve administering the compound to tumor-bearing mice, followed by assessment of CRBN degradation in tissues and evaluation of pharmacological effects. Further studies are needed to establish its in vivo efficacy and safety profile.
|
| ADME/Pharmacokinetics |
ZXH-4-130 TFA has a molecular formula of C48H59F3N6O11S and a molecular weight of 985.08. The CAS number is 2711006-67-4. The compound should be stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 1 year. It is soluble in DMSO and other common organic solvents. The compound is intended for research use only and is not approved for therapeutic use in humans.
|
| Toxicity/Toxicokinetics |
The toxicity profile of ZXH-4-130 TFA is not extensively characterized, as it is a research compound. It is intended for research use only and is not approved for therapeutic use in humans. Standard laboratory safety practices, including the use of personal protective equipment and handling in a fume hood, are recommended. The compound should be handled with care due to its potent biological activity.
|
| References | |
| Additional Infomation |
ZXH-4-130 TFA (CAS 2711006-67-4) is a highly potent and selective hetero-PROTAC (CRBN-VHL compound) that efficaciously mediates the degradation of CRBN. It induces approximately 80% CRBN degradation at 10 nM in MM1.S cells. The compound is a CRBN-VHL class compound used as a chemical tool for targeted protein degradation research. It is not approved for clinical use and is intended for research purposes only.
|
| Molecular Formula |
C48H59F3N6O11S
|
|---|---|
| Molecular Weight |
985.08
|
| Exact Mass |
984.391
|
| CAS # |
2711006-67-4
|
| Related CAS # |
ZXH-4-130;2711006-66-3
|
| PubChem CID |
162640901
|
| Appearance |
Off-white to gray solid powder
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
16
|
| Rotatable Bond Count |
20
|
| Heavy Atom Count |
69
|
| Complexity |
1700
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
N1=CSC(C2C=CC(=CC=2)CNC([C@@H]2C[C@H](CN2C(=O)[C@H](C(C)(C)C)NC(CCCCCCCCCCOC2=CC=CC3=C2C(=O)N(C2CCC(NC2=O)=O)C3=O)=O)O)=O)=C1C.OC(=O)C(F)(F)F
|
| InChi Key |
QKDOGOBHFHCHMX-YYRHATPXSA-N
|
| InChi Code |
InChI=1S/C46H58N6O9S.C2HF3O2/c1-28-39(62-27-48-28)30-19-17-29(18-20-30)25-47-41(56)34-24-31(53)26-51(34)45(60)40(46(2,3)4)49-36(54)16-11-9-7-5-6-8-10-12-23-61-35-15-13-14-32-38(35)44(59)52(43(32)58)33-21-22-37(55)50-42(33)57;3-2(4,5)1(6)7/h13-15,17-20,27,31,33-34,40,53H,5-12,16,21-26H2,1-4H3,(H,47,56)(H,49,54)(H,50,55,57);(H,6,7)/t31-,33?,34+,40-;/m1./s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[11-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyundecanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO :~170 mg/mL (~172.57 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0151 mL | 5.0757 mL | 10.1515 mL | |
| 5 mM | 0.2030 mL | 1.0151 mL | 2.0303 mL | |
| 10 mM | 0.1015 mL | 0.5076 mL | 1.0151 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
