2. Cell Cycle/DNA Damage
  3. DNA/RNA Synthesis
  4. BPN-15477

BPN-15477 is an orally active, blood-brain barrier-permeable splicing modulator compound (SMC). BPN-15477 restores the correct splicing of exon 20 of the elongator complex protein 1 (ELP1) (EC50 = 1.9 μM), thereby significantly increasing the in vivo functional protein levels in all tissues including the brain. BPN-15477 can be used in the research of familial dysautonomia, such as frontotemporal dementia.

For research use only. We do not sell to patients.

BPN-15477

BPN-15477 Chemical Structure

CAS No. : 1971086-99-3

Size Price Stock Quantity
Free Sample (0.1 - 0.2 mg)   Apply Now  
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 In-stock
Solution
10 mM * 1 mL in DMSO In-stock
Solid
5 mg In-stock
10 mg In-stock
25 mg In-stock
50 mg In-stock
100 mg In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 1 Customer Validation

BPN-15477 Related Antibodies

Top Publications Citing Use of Products

View All DNA/RNA Synthesis Isoform Specific Products:

View All Isoforms
RNASE L DNA Polymerases RNA Polymerases Helicases DNA Ligase

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

BPN-15477 is an orally active, blood-brain barrier-permeable splicing modulator compound (SMC). BPN-15477 restores the correct splicing of exon 20 of the elongator complex protein 1 (ELP1) (EC50 = 1.9 μM), thereby significantly increasing the in vivo functional protein levels in all tissues including the brain. BPN-15477 can be used in the research of familial dysautonomia, such as frontotemporal dementia[1][2].

In Vitro

BPN-15477 (24 h) potently increases the inclusion rate of ELP1 exon 20 in HEK293T cells transfected with Rluc-FD-Fluc, with an EC50 of 1.9 μM[1].
BPN-15477 (0.3-60 μM; 24 h) dose-dependently increases the inclusion rate of ELP1 exon 20 in fibroblasts from FD patients, reaching up to 99.6% after treatment with 60 μM for 24 h[1].
BPN-15477 (30 μM; 7 days) selectively regulates genome-wide transcriptome splicing in wild-type human fibroblasts, altering the inclusion or exclusion of 934 exon triplets after 7 days of treatment at 30 μM, and RT-PCR validates the results of RNA-seq[1].
BPN-15477 (60 μM; 24 h) regulates the splicing of intermediate exons in HEK293T cells transfected with PARP6 and SETD5 minigenes, which is consistent with the prediction results of the CNN model; specifically, treatment with 60 μM for 24 h increases the inclusion rate of PARP6 exons and decreases that of SETD5 exons[1].
BPN-15477 (60 μM; 24-5 days) corrects aberrant splicing in disease-related models: after treatment at 60 μM for 24 to 5 days, it increases the inclusion rate of LIPA exon 8 in fibroblasts from patients with c.894G > A, elevates the inclusion rate of CFTR exon 18 in minigene cells with c.2988G > A, enhances the inclusion rate of MLH1 exon 17 in minigene cells with c.1989G > A, and reduces the inclusion rate of MAPT exon 10 in minigene cells with c.1866 and 16C > T[1].
BPN-15477 (60 μM; 5-7 days) increases the level of functional LIPA protein in fibroblasts from patients with c.894G > A, as well as the level of mature CFTR protein in Flp-In-293 cells expressing the c.2988G > A minigene following treatment with 60 μM for 5 to 7 days[1].
BPN-15477 (0.3-10 μM; 3 days) dose-dependently restores the function of CFTR chloride channels in CFBE cells, with maximal function achieved at a concentration of 3 μM after 3 days of treatment[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

BPN-15477 Related Antibodies

RT-PCR[1]

Cell Line: Familial dysautonomia (FD) patient fibroblasts carrying the ELP1 c.2204+6T>C mutation
Concentration: 0.3, 1, 3, 10, 30 and 60 μM
Incubation Time: 24 h
Result: Increased ELP1 exon 20 inclusion in a dose-dependent manner, reaching 99.6% inclusion at 60 μM, compared to 51.1% inclusion with DMSO vehicle.

RT-PCR[1]

Cell Line: HEK293T cells transfected with PARP6 or SETD5 minigenes (wild-type and mutated)
Concentration: 60 μM
Incubation Time: 24 h
Result: Increased middle exon inclusion in wild-type PARP6 minigene from 33.0% to 56.2% and in mutated PARP6 minigene from 2.9% to 13.2%.
Decreased middle exon inclusion in wild-type SETD5 minigene from 18.7% to 13.1% and in mutated SETD5 minigene from 93.0% to 83.4%.
Matched CNN model predictions of treatment response.

RT-PCR[1]

Cell Line: LIPA patient fibroblasts carrying the c.894G>A mutation; Flp-In-293 cells stably expressing c.2988G>A CFTR expression minigene; HEK293T cells transfected with c.1989G>A MLH1 minigene; HEK293 cells stably expressing c.1866+16C>T MAPT minigene
Concentration: 60 μM
Incubation Time: 24 h (LIPA, MLH1, MAPT cells); 5 days (CFTR minigene cells)
Result: Increased LIPA exon 8 inclusion from 54.2% (DMSO) to 66.1% in LIPA patient fibroblasts.
Increased CFTR exon 18 inclusion from 4.4% (DMSO) to 13.2% in CFTR minigene cells.
Increased MLH1 exon 17 inclusion from 5.1% (DMSO) to 11.1% in MLH1 minigene cells.
Decreased MAPT exon 10 inclusion from 90.9% (DMSO) to 87.0% in MAPT minigene cells.

Western Blot Analysis[1]

Cell Line: LIPA patient fibroblasts carrying the c.894G>A mutation; Flp-In-293 cells stably expressing c.2988G>A CFTR expression minigene
Concentration: 60 μM
Incubation Time: 7 days (LIPA fibroblasts); 5 days (CFTR minigene cells)
Result: Increased functional LIPA protein levels to ~10% of wild-type levels, compared to near-undetectable levels with DMSO in LIPA patient fibroblasts.
Increased mature CFTR protein levels to ~20% of wild-type levels, compared to ~3% with DMSO in CFTR minigene cells.
In Vivo

BPN-15477 (10-100 mg/kg; p.o.; daily; 7 days) increases full-length ELP1 transcript in a dose-dependent manner and achieves at least a two-fold increase in functional ELP1 protein across multiple tissues, including brain, in TgFD9 transgenic mice[1].
BPN-15477 (70 mg/kg/day; p.o.; daily; 5 weeks) achieves near-complete correction of ELP1 exon 20 splicing in the retina of humanized FD transgenic mice, with mean exon 20 inclusion reaching ~95%[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: TgFD9 transgenic mice (adult)[1]
Dosage: 10 mg/kg; 30 mg/kg; 60 mg/kg; 100 mg/kg
Administration: p.o.; daily; 7 days
Result: Increased full-length ELP1 transcript in a dose-dependent manner across all tissues.
Achieved at least a two-fold increase in functional ELP1 protein in brain, liver, kidney, heart, and skin at all tested doses.
Showed good tolerability, with no weight loss or adverse effects observed in treated groups.
Animal Model: mixed C57BL/6J and C57BL/6N background (both sexes, humanized transgenic carrying ELP1 transgene with FD splice mutation, TgFD9)[2]
Dosage: 70 mg/kg/day
Administration: p.o.; daily; 5 weeks
Result: Increased ELP1 exon 20 inclusion in the retina from a mean of 52% in untreated mice to a mean of 95% in treated mice, representing near-complete correction of the splicing defect.
Molecular Weight

259.69

Formula

C12H10ClN5
CAS No.
Appearance

Solid

Color

White to light yellow

SMILES

ClC1=NC2=C(C=CN2)C(NCC3=CC=NC=C3)=N1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (96.27 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.8507 mL 19.2537 mL 38.5075 mL 96.2686 mL
5 mM 0.7701 mL 3.8507 mL 7.7015 mL 19.2537 mL
10 mM 0.3851 mL 1.9254 mL 3.8507 mL 9.6269 mL
15 mM 0.2567 mL 1.2836 mL 2.5672 mL 6.4179 mL
20 mM 0.1925 mL 0.9627 mL 1.9254 mL 4.8134 mL
25 mM 0.1540 mL 0.7701 mL 1.5403 mL 3.8507 mL
30 mM 0.1284 mL 0.6418 mL 1.2836 mL 3.2090 mL
40 mM 0.0963 mL 0.4813 mL 0.9627 mL 2.4067 mL
50 mM 0.0770 mL 0.3851 mL 0.7701 mL 1.9254 mL
60 mM 0.0642 mL 0.3209 mL 0.6418 mL 1.6045 mL
80 mM 0.0481 mL 0.2407 mL 0.4813 mL 1.2034 mL
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

BPN-15477 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

BPN-154771971086-99-3BPN15477BPN 15477DNA/RNA Synthesispre-mRNA splicingMLH1LIPAHEK293T cellsELP1 exon 20MAPTCFTRTgFD9 transgenic micefamilial dysautonomiaELP1 proteinInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Requested Quantity *

Applicant Name *

 

Salutation

Email Address *

 

Phone Number *

Department

 

Organization Name *

City

State

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
BPN-15477
Cat. No.:
HY-147149
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

SAFETY DATA SHEET (SDS)

English - EN (251 KB) Français - FR (251 KB) Deutsch - DE (251 KB) Norwegian - NO (251 KB) Español - ES (251 KB) Swedish - SV (251 KB) Italian - IT (251 KB) Korean - KR (251 KB) Portuguese - PT (251 KB)

Request for HNMR Report

We have received your request and will respond to you as soon as possible.