| Size | Price | Stock | Qty |
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| Targets |
The primary target is H-PGDS (Hematopoietic Prostaglandin D Synthase), a key enzyme in the arachidonic acid cascade that catalyzes the isomerization of PGH2 to PGD2. By recruiting H-PGDS to an E3 ubiquitin ligase, the PROTAC induces the ubiquitination and subsequent proteasomal degradation of H-PGDS. This degradation leads to a potent suppression of PGD2 production, a pro-inflammatory lipid mediator.
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| ln Vitro |
In KU812 cells, PROTAC(H-PGDS)-7 can successfully block the synthesis of prostaglandin D2 (PGD2) [1].
PROTAC(H-PGDS)-7 shows potent suppression of prostaglandin D2 (PGD2) production in KU812 cells. In biochemical assays, it functions as a molecular glue degrader with a DC50 (half-maximal degradation concentration) of 17.3 pM (picomolar). This indicates extremely potent degradation efficiency. By completely eliminating the H-PGDS protein, the compound effectively shuts down the production of PGD2, an inflammatory mediator involved in various allergic and inflammatory diseases. |
| ln Vivo |
While specific in vivo data for this exact compound is not detailed, PROTAC(H-PGDS)-7 is intended for in vivo studies of Duchenne muscular dystrophy (DMD) and other H-PGDS-related inflammatory diseases. By degrading H-PGDS and inhibiting PGD2 production, the compound is expected to reduce inflammation and fibrosis in disease models. A typical protocol would involve intraperitoneal or oral administration of the compound to a mouse model of DMD (mdx mice) to measure its effect on muscle inflammation and function.
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| Enzyme Assay |
The assay does not involve an enzyme reaction; it measures the cooperative ternary complex formation (the “molecular glue” mechanism). Purified H-PGDS protein and the E3 ligase complex (e.g., CRL4CRBN) are mixed in a buffer with varying concentrations of PROTAC(H-PGDS)-7. The formation of the ternary complex is measured using an AlphaScreen or TR-FRET-based assay with appropriately labeled proteins. The EC50 for complex formation is a measure of potency.
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| Cell Assay |
KU812 (human basophilic leukemia) cells are used to measure cellular PGD2 production. The cells are treated with varying concentrations of PROTAC(H-PGDS)-7 for a defined period (e.g., 24 hours). After treatment, the cells are stimulated with a calcium ionophore (e.g., A23187) to induce PGD2 production. The levels of PGD2 in the cell culture supernatant are then measured using a competitive ELISA kit. The EC50 for inhibition of PGD2 production is calculated. To confirm degradation, cell lysates are analyzed by Western blot for H-PGDS protein levels.
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| Animal Protocol |
In vivo efficacy can be assessed in a mouse model of Duchenne muscular dystrophy (mdx mice). Mice are administered PROTAC(H-PGDS)-7 (e.g., intraperitoneally at 5-10 mg/kg) daily for several weeks. Muscle strength is measured using a grip strength meter. At the end of the study, muscle tissues (e.g., diaphragm, quadriceps) are collected for histological analysis of inflammation (e.g., H&E staining) and fibrosis (e.g., Sirius Red staining). PGD2 levels in plasma and muscle homogenates are measured by LC-MS to confirm target engagement.
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| ADME/Pharmacokinetics |
Specific PK parameters for PROTAC(H-PGDS)-7 are not detailed. As a PROTAC, its molecular weight is approximately 742.79 g/mol, which is at the upper limit of Lipinski's Rule of Five, potentially affecting oral bioavailability and membrane permeability. Its development as an H-PGDS degrader suggests a need for sufficient stability and cellular penetration to access the intracellular target.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PROTAC(H-PGDS)-7 are not detailed. As an H-PGDS degrader, its primary toxicity would likely be related to the pharmacological consequences of PGD2 depletion, which may include effects on platelet aggregation and allergic response modulation. Standard 28-day repeat-dose toxicity studies in rodents would assess the safety margin and identify any potential off-target toxicities.
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| References | |
| Additional Infomation |
PROTAC(H-PGDS)-7 is an advanced research-grade PROTAC degrader. It represents a chemical biology approach to treating H-PGDS-related diseases by degrading the enzyme, rather than simply inhibiting its active site. This is the first reported molecular glue degrader for H-PGDS. As of the latest updates, this compound is in the pre-clinical research phase and has not yet been approved for clinical use.
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| Molecular Formula |
C40H38N8O7
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|---|---|
| Molecular Weight |
742.779128551483
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| Exact Mass |
742.286
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| CAS # |
2761281-50-7
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| PubChem CID |
162679258
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
55
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| Complexity |
1440
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(OC2=CC=CC=C2)=NC=C(C(NC2=CC=C(N3CCC(C(N4CCN(C5=CC=CC6=C5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)=O)CC3)C=C2)=O)C=N1
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| InChi Key |
KQNXUQJGOJWQGL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C40H38N8O7/c49-33-14-13-32(36(51)44-33)48-38(53)30-7-4-8-31(34(30)39(48)54)46-19-21-47(22-20-46)37(52)25-15-17-45(18-16-25)28-11-9-27(10-12-28)43-35(50)26-23-41-40(42-24-26)55-29-5-2-1-3-6-29/h1-12,23-25,32H,13-22H2,(H,43,50)(H,44,49,51)
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| Chemical Name |
N-[4-[4-[4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]piperazine-1-carbonyl]piperidin-1-yl]phenyl]-2-phenoxypyrimidine-5-carboxamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~134.63 mM)
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| 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 | 1.3463 mL | 6.7315 mL | 13.4629 mL | |
| 5 mM | 0.2693 mL | 1.3463 mL | 2.6926 mL | |
| 10 mM | 0.1346 mL | 0.6731 mL | 1.3463 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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