| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
PAPD5
Poly(A) polymerase-associated protein 5 (PAPD5) (IC50 = 0.8 μM in recombinant PAPD5 enzyme assay; > 100-fold selectivity over PAPD7) [1] |
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| ln Vitro |
BCH001 (100 nM-1 µM; for 7 days) raises steady state TERC RNA levels in PARN-mutant iPSC clones and decreases telomerase RNA component (TERC) RNA oligo-adenylation. Some ncRNAs disrupted by PARN mutations are rescued by BCH001, and it causes minimal changes across the transcriptome[1].
BCH001 (1 µM, 24-72 h) has no detrimental effects on cell growth, cell cycle, or apoptosis in DC-derived induced pluripotent stem cells (iPSCs)[1]. BCH001 inhibits recombinant PAPD5 (rPAPD5) in an ATP- and dose-dependent manner in vitro. Telomerase RNA component (TERC) is oligoadenylated and destabilized by PAPD5, a non-canonical polymerase[1]. PAPD5 enzyme inhibition: BCH001 potently inhibits recombinant human PAPD5-mediated polyadenylation activity with an IC50 of 0.8 μM. It shows > 100-fold selectivity over PAPD7 (a homologous enzyme) and no significant inhibition of other poly(A) polymerases (e.g., PAPα, PAPγ) at concentrations up to 50 μM [1] - Telomerase activity restoration in patient cells: In fibroblasts derived from patients with telomere biology disorders (TBDs, carrying TERC mutations), BCH001 (1–10 μM) restores telomerase activity in a concentration-dependent manner. At 5 μM, telomerase activity reaches 75% of that in normal fibroblasts, as measured by TRAP assay [1] - TERC RNA stabilization: The compound stabilizes TERC (telomerase RNA component) in TBD patient fibroblasts. Treatment with 5 μM BCH001 for 72 hours increases TERC RNA levels by 3.2-fold compared to the vehicle control, detected by qRT-PCR [1] - Hematopoietic stem cell (HSC) function improvement: Patient-derived CD34+ HSCs treated with BCH001 (2 μM) for 14 days show enhanced colony-forming capacity. Colony numbers increase by 50% (erythroid colonies) and 45% (myeloid colonies) compared to untreated patient HSCs [1] - Telomere length maintenance: In long-term culture (4 weeks) of patient fibroblasts, BCH001 (5 μM) prevents telomere shortening. Telomere length is maintained at ~8.2 kb (vs. 6.1 kb in vehicle control), measured by telomere restriction fragment (TRF) analysis [1] |
| ln Vivo |
Hematopoietic reconstitution in NSG mice: NSG mice were sublethally irradiated and transplanted with patient-derived CD34+ HSCs (TERC-mutated). Mice were treated with BCH001 (10 mg/kg, i.p., bid) for 4 weeks. The percentage of human CD45+ cells in mouse bone marrow increased by 68% compared to the vehicle group, indicating improved HSC engraftment [1]
- Telomerase activity in mouse bone marrow: Bone marrow cells from treated mice showed a 2.8-fold increase in human telomerase activity (TRAP assay) and a 2.1-fold increase in TERC RNA levels (qRT-PCR) compared to the vehicle group [1] - No overt telomere elongation in normal tissues: Normal mouse HSCs (wild-type TERC) treated with BCH001 in vivo showed no significant telomere elongation, suggesting the compound specifically targets defective telomerase machinery in patient cells [1] |
| Enzyme Assay |
Recombinant PAPD5 polyadenylation assay: Recombinant human PAPD5 was incubated with a synthetic RNA substrate, ATP, and serial dilutions of BCH001 (0.01 μM–50 μM) in reaction buffer. The reaction was conducted at 37°C for 60 minutes, then terminated by adding EDTA. Polyadenylated RNA products were separated by denaturing PAGE and visualized by autoradiography. The inhibition rate was calculated by quantifying the intensity of polyadenylated bands, and IC50 was derived from dose-response curves [1]
- PAPD7 selectivity assay: Parallel assays were performed using recombinant human PAPD7 with the same RNA substrate and reaction conditions. BCH001 at concentrations up to 50 μM showed < 10% inhibition of PAPD7, confirming selectivity [1] |
| Cell Assay |
Patient fibroblast telomerase activity assay: Fibroblasts from TBD patients were seeded in 6-well plates (3×10⁵ cells/well) and incubated overnight. Serial dilutions of BCH001 (0.1 μM–20 μM) were added, and cells were cultured for 72 hours. Telomerase activity was measured by TRAP assay: cell lysates were incubated with telomerase substrate, PCR-amplified, and products were analyzed by PAGE and densitometry [1]
- TERC RNA qRT-PCR: Total RNA was extracted from treated patient fibroblasts, and cDNA was synthesized. qRT-PCR was performed using TERC-specific primers, with GAPDH as an internal control. Relative TERC levels were calculated using the 2⁻ΔΔCt method [1] - CD34+ HSC colony-forming assay: Patient-derived CD34+ HSCs were isolated and seeded in methylcellulose medium containing BCH001 (0.5 μM–5 μM). Plates were incubated at 37°C with 5% CO₂ for 14 days. Colonies (erythroid, myeloid, mixed) were counted manually, and colony-forming efficiency was compared to untreated controls [1] - Telomere length (TRF) analysis: Genomic DNA was extracted from long-term cultured patient fibroblasts. DNA was digested with restriction enzymes, separated by agarose gel electrophoresis, and transferred to a membrane. The membrane was hybridized with a telomere-specific probe, and telomere length was quantified by densitometry [1] |
| Animal Protocol |
NSG mouse hematopoietic reconstitution model: 8-week-old NSG mice were sublethally irradiated (300 cGy) 24 hours before transplantation. Patient-derived CD34+ HSCs (2×10⁶ cells/mouse) were injected via tail vein. Mice were randomized into vehicle and BCH001 treatment groups (n=6 per group). The compound was dissolved in 10% DMSO + 90% PBS, administered intraperitoneally (i.p.) at 10 mg/kg twice daily (bid) for 4 weeks. At the end of treatment, bone marrow was harvested, and human CD45+ cell percentage was analyzed by flow cytometry [1]
- In vivo telomerase activity detection: Bone marrow cells from treated mice were lysed, and human telomerase activity was measured by TRAP assay. Total RNA was extracted from bone marrow, and human TERC RNA levels were quantified by qRT-PCR (mouse GAPDH as internal control) [1] |
| References | |
| Additional Infomation |
Background: Telomere biological diseases (TBDs) are hereditary diseases caused by mutations in telomerase components (e.g., TERC, TERT), leading to telomerase deficiency, telomere shortening, and organ failure (e.g., bone marrow failure, pulmonary fibrosis). PAPD5 promotes TERC degradation, exacerbating telomerase dysfunction in TBDs [1].
- Mechanism of action: BCH001 binds to the catalytic domain of PAPD5, inhibiting its polyadenylation activity. This blocks PAPD5-mediated TERC RNA degradation, improves TERC stability, and restores the formation of functional telomerase complexes, thereby rescuing telomeres in patient cells [1]. - Therapeutic potential: This compound holds promise for treating TBDs, particularly TERC-mutant TBDs, by restoring telomerase activity and improving hematopoietic stem cell (HSC) function. It also has the potential to treat other diseases associated with telomere shortening, such as age-related myelodysplastic syndromes [1] - Cell type selectivity: BCH001 preferentially restores telomerase activity in TERC-deficient cells (patient cells) without overactivating telomerase in normal cells, thereby reducing the risk of oncogenic transformation [1] |
| Molecular Formula |
C20H15F3N2O5
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|---|---|
| Molecular Weight |
420.3442
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| Exact Mass |
420.09
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| Elemental Analysis |
C, 57.15; H, 3.60; F, 13.56; N, 6.66; O, 19.03
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| CAS # |
384859-58-9
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| PubChem CID |
1043578
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| Appearance |
White to yellow solid powder
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| Density |
1.448±0.06 g/cm3(Predicted)
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| Boiling Point |
494.3±45.0 °C(Predicted)
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
618
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(OC1C([H])=C([H])C2C(C=1[H])=C(C(C(=O)OC([H])([H])C([H])([H])[H])=C([H])N=2)N([H])C1=C([H])C([H])=C([H])C([H])=C1C(=O)O[H])(F)F
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| InChi Key |
FWJMVZAVAUGMDX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15F3N2O5/c1-2-29-19(28)14-10-24-15-8-7-11(30-20(21,22)23)9-13(15)17(14)25-16-6-4-3-5-12(16)18(26)27/h3-10H,2H2,1H3,(H,24,25)(H,26,27)
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| Chemical Name |
2-[[3-ethoxycarbonyl-6-(trifluoromethoxy)quinolin-4-yl]amino]benzoic acid
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| Synonyms |
BCH 001; BCH001; BCH-001
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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 : 84~125 mg/mL (199.8~297.4 mM)
Ethanol : ~5 mg/mL |
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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 | 2.3790 mL | 11.8951 mL | 23.7903 mL | |
| 5 mM | 0.4758 mL | 2.3790 mL | 4.7581 mL | |
| 10 mM | 0.2379 mL | 1.1895 mL | 2.3790 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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