| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Pociredir specifically targets the Embryonic Ectoderm Development (EED) protein. EED is a crucial component of the Polycomb Repressive Complex 2 (PRC2). The compound binds to EED, which disrupts the PRC2 complex's ability to catalyze the trimethylation of histone H3 at lysine 27 (H3K27me3). This modulation of the epigenetic machinery leads to increased expression of the gamma-globin gene and subsequent production of fetal hemoglobin (HbF).
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|---|---|
| ln Vitro |
Pociredir inhibits PRC2 via binding to EED, which generates strong HbF protein production in both cell and mouse models[2].
In vitro studies demonstrate that Pociredir effectively inhibits the function of the PRC2 complex by binding to EED. This results in a robust induction of fetal hemoglobin (HbF) protein expression in cellular models. HbF induction is a validated therapeutic strategy for ameliorating the clinical symptoms of sickle cell disease, making Pociredir a key tool for studying hemoglobin switching and related epigenetic pathways. |
| ln Vivo |
In vivo, Pociredir has been shown to induce HbF protein expression in murine models, confirming its oral bioavailability and biological activity. It is being investigated as a potential treatment for sickle cell disease and beta-thalassemia. The compound acts by elevating the expression of HbF, a form of hemoglobin that is normally replaced in adults, to compensate for defective adult hemoglobin.
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| Enzyme Assay |
For a cell-free assay, the PRC2 complex (including EED, EZH2, and SUZ12) is combined with a radiolabeled methyl donor, S-adenosyl-L-methionine (SAM), and a peptide substrate representing histone H3 (amino acids 1-40). The reaction progress is measured by the transfer of the radioactive methyl group to the peptide. The compound is added to the reaction mixture, and its inhibitory activity (IC50) is calculated based on the reduction of methyltransferase activity.
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| Cell Assay |
In cellular assays, human erythroid progenitor cells are cultured and treated with various concentrations of Pociredir. After several days of treatment, the cells are harvested. The levels of HbF protein expression are quantified by Enzyme-Linked Immunosorbent Assay (ELISA) or by flow cytometry after intracellular staining for HbF. The compound's potency is evaluated based on the EC50 for HbF induction.
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| Animal Protocol |
In vivo efficacy is assessed in humanized mouse models that express human hemoglobin. These mice are administered Pociredir orally at regular intervals. Blood samples are collected over a time course to measure the percentage of HbF-positive red blood cells (F-cells) using flow cytometry or HPLC. The endpoint is a significant and sustained increase in HbF expression. The study aims to evaluate the compound's ability to induce HbF and ameliorate disease pathology.
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| ADME/Pharmacokinetics |
Pociredir is described as a potent and orally active compound, indicating it has favorable drug-like properties and good oral bioavailability. This allows it to be administered via oral gavage in animal models. However, detailed data on its absorption, distribution, metabolism, and excretion (ADME) are not provided in the summary text but are part of its ongoing preclinical profile.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology reports for Pociredir are not included in the available literature. However, its safety profile is a key component of its preclinical development for chronic diseases like sickle cell disease. In the described in vivo models, it is being evaluated for efficacy, and tolerability is likely assessed by monitoring animal body weight, behavior, and clinical pathology markers. Current descriptions do not report adverse side effects.
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| References | |
| Additional Infomation |
Pociredir is a pioneering compound targeting EED, a core component of the PRC2 complex, to induce fetal hemoglobin (HbF). The therapeutic premise is that pharmacologically increasing HbF levels can compensate for the defective adult hemoglobin in sickle cell disease and beta-thalassemia. This epigenetic approach represents a disease-modifying strategy. It has been investigated in preclinical studies and is a candidate for clinical development for hemoglobinopathies.
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| Molecular Formula |
C22H18FN5O2
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|---|---|
| Molecular Weight |
403.409027576447
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| Exact Mass |
403.144
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| CAS # |
2490676-18-9
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| Related CAS # |
Pociredir hydrochloride;2490676-19-0
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| PubChem CID |
155286052
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| Appearance |
White to light yellow solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
30
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| Complexity |
628
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=CC=C2C3=C1CNC1=C(C=C(C4=CC=CN=C4C)C4=NN=CN14)OC[C@@H]3CO2
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| InChi Key |
JQBUTSBIFNKJMW-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C22H18FN5O2/c1-12-14(3-2-6-24-12)15-7-19-22(28-11-26-27-21(15)28)25-8-16-17(23)4-5-18-20(16)13(9-29-18)10-30-19/h2-7,11,13,25H,8-10H2,1H3/t13-/m0/s1
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| Chemical Name |
(15S)-21-fluoro-10-(2-methylpyridin-3-yl)-13,17-dioxa-3,5,7,8-tetrazapentacyclo[13.6.1.04,12.05,9.018,22]docosa-1(21),4(12),6,8,10,18(22),19-heptaene
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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 |
| 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: 25 mg/mL (61.97 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.16 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 1 mg/mL (2.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4789 mL | 12.3943 mL | 24.7887 mL | |
| 5 mM | 0.4958 mL | 2.4789 mL | 4.9577 mL | |
| 10 mM | 0.2479 mL | 1.2394 mL | 2.4789 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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