| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
BPN-15477 targets the pre-mRNA splicing machinery, specifically interacting with components that regulate ELP1 exon 20 inclusion. It is a small molecule splicing modulator that corrects the pathogenic ELP1 splicing defect without affecting other genes or inducing global splicing changes.
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| ln Vitro |
In cell-free systems using mini-gene splicing reporter assays, BPN-15477 restores correct ELP1 exon 20 inclusion with an EC50 of 1.9 uM. It selectively promotes inclusion of the pathogenic exon without affecting other splice sites or inducing non-specific splicing alterations.
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| ln Vivo |
In fibroblast cells derived from FD patients, BPN-15477 (1-20 uM) significantly increases full-length ELP1 mRNA and protein levels in a dose-dependent manner. Correct splicing is restored without evidence of toxicity at effective concentrations. It rescues ELP1 protein expression and ameliorates cellular phenotypes associated with ELP1 deficiency.
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| Enzyme Assay |
Cell-free splicing assays are performed using nuclear extracts and a splicing reporter mini-gene containing ELP1 exon 20 flanked by intronic sequences. The compound is added at various concentrations (0.1-100 uM), and splicing products are analyzed by RT-PCR and gel electrophoresis. EC50 for exon 20 inclusion is calculated from dose-response curves. FD patient-derived fibroblast cell lines (or ELP1 splicing reporter cell lines) are treated with BPN-15477 (0.1-30 uM) for 48-72 hours. ELP1 mRNA splicing is analyzed by RT-PCR and qRT-PCR. ELP1 protein levels are quantified by Western blot. Cell viability is assessed by MTT to confirm lack of cytotoxicity. Cytotoxicity is monitored to ensure absence of off-target toxicity.
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| Animal Protocol |
In TgFD9 mice (a mouse model of familial dysautonomia), BPN-15477 is administered orally at 70 mg/kg. Brain ELP1 protein levels increase approximately 1.5-fold compared to vehicle-treated controls. Efficacy is observed in all tissues examined, including brain, confirming CNS penetration. The compound is well-tolerated at this dose. Oral bioavailability is good with CNS penetration confirmed in preclinical studies.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic studies show that BPN-15477 has favorable oral bioavailability and brain penetration properties. Following oral administration in rodents, peak plasma concentrations are reached within 2-4 hours. The compound distributes widely, with significant levels detected in the brain (CNS penetrant). Elimination half-life is approximately 6-12 hours, supporting once-daily dosing in animal studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies in rodents at therapeutic doses (≤70 mg/kg oral) show a tolerable safety profile without significant adverse effects. Higher doses have not been systematically evaluated in published literature. BPN-15477 is not approved for human use and is strictly for research applications. Standard safety precautions for laboratory chemicals should be followed.
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| Additional Infomation |
This is a research-grade splicing modulator, not an approved drug. It has therapeutic potential for familial dysautonomia and other human genetic diseases caused by splicing defects, including frontotemporal dementia (MAPT) and cystic fibrosis (CFTR). Molecular formula: C12H10ClN5; molecular weight: 259.69. Purity: ≥98%.
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| Molecular Formula |
C12H10CLN5
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|---|---|
| Molecular Weight |
259.69
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| Exact Mass |
259.062
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| CAS # |
1971086-99-3
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| PubChem CID |
134480553
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| Appearance |
White to light yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
18
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| Complexity |
271
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CNC2=C1C(=NC(=N2)Cl)NCC3=CC=NC=C3
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| InChi Key |
JAAXPOGNLKNTBW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H10ClN5/c13-12-17-10-9(3-6-15-10)11(18-12)16-7-8-1-4-14-5-2-8/h1-6H,7H2,(H2,15,16,17,18)
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| Chemical Name |
2-chloro-N-(pyridin-4-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
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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 (~96.27 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 | 3.8507 mL | 19.2537 mL | 38.5075 mL | |
| 5 mM | 0.7701 mL | 3.8507 mL | 7.7015 mL | |
| 10 mM | 0.3851 mL | 1.9254 mL | 3.8507 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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