| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
EED (embryonic ectoderm development; component of PRC2 complex).
|
|---|---|
| ln Vitro |
Pociredir hydrochloride binds to EED to inhibit PRC2, hence inducing robust production of HbF protein in both mouse and cell models[2].
Pociredir hydrochloride binds to EED to inhibit PRC2 activity, leading to the induction of robust HbF protein expression in cellular models. This reactivation of the gamma-globin gene (which encodes the beta-like chain of fetal hemoglobin) is the therapeutic mechanism for treating sickle cell disease (SCD) and beta-thalassemia. The compound likely disrupts the binding of EED to H3K27me3, preventing PRC2 activity. |
| ln Vivo |
Pociredir hydrochloride induces HbF protein expression in murine models (e.g., transgenic mice carrying the human beta-globin locus). Oral administration leads to increased HbF levels in red blood cells and improvement in hematological parameters. In preclinical disease models, this translates to reduced red blood cell sickling (in SCD models) and improved red blood cell survival.
|
| Enzyme Assay |
Assay: In vitro EED binding assay. Protocol: Recombinant EED protein is incubated with varying concentrations of Pociredir hydrochloride (0.1-1000 nM) and a fluorescently labeled trimethylated H3K27me3 peptide in a TR-FRET assay buffer. The ability of the compound to displace the peptide from EED is measured by the decrease in FRET signal. IC50 values are calculated for the displacement activity.
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| Cell Assay |
Cells: Primary human erythroid progenitor cells (CD34+ cells) differentiated in culture. Protocol: Cells are treated with Pociredir hydrochloride (0.1-1000 nM) for 7-14 days during erythroid differentiation. HbF levels are quantified by HPLC analysis of globin chains (gamma-globin vs. beta-globin). Alternatively, gamma-globin mRNA is measured by qRT-PCR. Cell viability is assessed by trypan blue exclusion. HbF induction is dose-dependent.
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| Animal Protocol |
Animal Model: Humanized beta-globin locus transgenic mice or SCD mouse models. Protocol: Mice are administered Pociredir hydrochloride orally (e.g., 10-100 mg/kg) once daily for 2-4 weeks. Blood samples are collected at various time points. HbF levels are measured by HPLC. Reticulocyte counts and red blood cell indices are measured. In SCD models, red blood cell sickling is assessed under hypoxic conditions. Efficacy is determined by comparing HbF levels to vehicle control.
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| ADME/Pharmacokinetics |
Pociredir hydrochloride is orally bioavailable with good exposure. It is absorbed rapidly after oral administration, and its PK profile supports once-daily dosing. Its half-life in plasma is sufficient to maintain PRC2 inhibition and gamma-globin gene reactivation over the dosing interval. The compound is likely metabolized in the liver and excreted through bile and urine, as is common for small-molecule epigenetic modulators.
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| Toxicity/Toxicokinetics |
No specific toxicity data published; as an EED inhibitor, Pociredir may have on-target effects on PRC2 in other tissues. PRC2 is a master regulator of gene expression during development and cell fate. In adult animals, inhibition of PRC2 can cause bone marrow suppression, anemia, and gastrointestinal toxicity. However, the short-term use of Pociredir in SCD may be feasible. Long-term safety has not been fully evaluated in clinical trials.
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| References | |
| Additional Infomation |
Pociredir hydrochloride (FTX-6058 hydrochloride) was developed by Fulcrum Therapeutics. It has been evaluated in Phase 1 clinical trials for the treatment of sickle cell disease (SCD) and beta-thalassemia. In these studies, FTX-6058 was generally well-tolerated and showed dose-dependent increases in HbF mRNA and protein levels. However, in 2023, Fulcrum announced a strategic shift and discontinued the development of FTX-6058 due to a portfolio reprioritization, not due to safety concerns.
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| Molecular Formula |
C22H19CLFN5O2
|
|---|---|
| Molecular Weight |
439.87
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| Exact Mass |
439.121
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| CAS # |
2490676-19-0
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| Related CAS # |
Pociredir;2490676-18-9
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| PubChem CID |
165010517
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
31
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| Complexity |
628
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(C2=CC3=C(NCC4C(F)=CC=C5C=4[C@@](CO3)([H])CO5)N3C=NN=C23)=C(N=CC=C1)C.Cl
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| InChi Key |
JOYSKAVINOJMDD-ZOWNYOTGSA-N
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| InChi Code |
InChI=1S/C22H18FN5O2.ClH/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;1H/t13-;/m0./s1
|
| 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;hydrochloride
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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, avoid exposure to moisture. |
| 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 : 125 mg/mL (284.17 mM)
H2O : 2 mg/mL (4.55 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.73 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.
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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2734 mL | 11.3670 mL | 22.7340 mL | |
| 5 mM | 0.4547 mL | 2.2734 mL | 4.5468 mL | |
| 10 mM | 0.2273 mL | 1.1367 mL | 2.2734 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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