| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Elongator complex protein 1 (ELP1).
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| ln Vitro |
PTC258 (0.01 nM-0.01 μM; 48 h) effectively raises the levels of full-length ELP1 mRNA and protein in the fibroblasts of patients with familial dysautonomia (FD)[1].
In vitro studies show that PTC258 (0.01 nM-0.01 microM; 48 h) efficiently increases full-length ELP1 mRNA and protein expression in fibroblasts derived from familial dysautonomia (FD) patients. |
| ln Vivo |
PTC258 is well tolerated at 3–24 mg/kg PO once daily for three months. It increases the amount of functional protein in vivo in all studied organs, including the brain in a mouse model, and corrects the splicing of the ELP1 transcript[1].
In vivo, PTC258 (3-24 mg/kg; p.o.; once daily for 3 months) is well tolerated. It corrects the splicing of the ELP1 transcript and significantly increases functional ELP1 protein levels in all tested tissues, including the brain, in a mouse model. |
| Enzyme Assay |
In a non-cellular assay, recombinant ELP1 pre-mRNA substrate is incubated with HeLa nuclear extract and varying concentrations of PTC258. The reaction is analyzed by RT-PCR to detect correctly spliced ELP1 mRNA products. A concentration-dependent increase in full-length ELP1 mRNA is observed, confirming direct modulation of the splicing machinery without cellular interference.
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| Cell Assay |
The cellular assay involves culturing primary fibroblasts from FD patients. Cells are treated with a concentration range of PTC258 (0.01 nM-0.01 microM) for 48 hours. Following treatment, total RNA and protein are extracted. RT-PCR quantifies ELP1 mRNA levels, and Western blotting is used to detect ELP1 protein expression, demonstrating restoration of functional ELP1.
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| Animal Protocol |
Animal/Disease Models: Familial Dysautonomia (FD) Mouse model[1]
Doses: 3 mg/kg, 6 mg/kg, 12 mg/kg, 24 mg/kg Route of Administration: Oral gavage; one time/day for 3 month Experimental Results: Increased full-length ELP1 transcript in a dose-dependent manner. And also, it increased in functional ELP1 protein in the brain, trigeminal, liver, and quadricep. In the animal study, a mouse model of FD is used. PTC258 is administered orally once daily at doses of 3, 6, 12, and 24 mg/kg for up to 3 months. Tolerability is assessed by monitoring body weight and general health. At the study endpoint, tissues (including brain) are harvested to measure ELP1 mRNA and protein levels, confirming corrected splicing and increased functional protein. |
| ADME/Pharmacokinetics |
PTC258 is orally bioavailable. It is well-absorbed following oral administration and capable of crossing the blood-brain barrier, as demonstrated by increased ELP1 protein levels in the brain of treated mice. In vitro, it is stable and can be prepared in DMSO for stock solutions, with recommended in vivo formulation vehicles containing DMSO and PEG300.
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| Toxicity/Toxicokinetics |
PTC258 is reported to be well tolerated in mouse models when administered orally at doses of 3-24 mg/kg daily for three months, with no severe adverse events noted. No specific cytotoxicity studies are detailed, but the compound is intended for research use only and not for human consumption.
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| References |
[1]. Morini E, et al. Development of a novel oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia[J]. bioRxiv, 2022: 2022.11. 04.515198.
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| Additional Infomation |
The compound is a small molecule (MW: 351.92, C16H18ClN3S2). The primary mechanism involves modulating pre-mRNA splicing, specifically correcting the mis-splicing of the ELP1 gene. As of current data, it is in preclinical research stages and has not been approved for clinical use or entered clinical trials.
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| Molecular Formula |
C16H18CLN3S2
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|---|---|
| Molecular Weight |
351.917219638824
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| Exact Mass |
351.063
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| CAS # |
2476724-74-8
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| PubChem CID |
155066344
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| Appearance |
White to yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
373
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(SC2=C1N=C(C=C2NCC3=CC=CS3)Cl)C[C@H](C)N
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| InChi Key |
XBAVUBLRECEOPY-VIFPVBQESA-N
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| InChi Code |
InChI=1S/C16H18ClN3S2/c1-9(18)6-13-10(2)15-16(22-13)12(7-14(17)20-15)19-8-11-4-3-5-21-11/h3-5,7,9H,6,8,18H2,1-2H3,(H,19,20)/t9-/m0/s1
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| Chemical Name |
2-[(2S)-2-aminopropyl]-5-chloro-3-methyl-N-(thiophen-2-ylmethyl)thieno[3,2-b]pyridin-7-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.8416 mL | 14.2078 mL | 28.4155 mL | |
| 5 mM | 0.5683 mL | 2.8416 mL | 5.6831 mL | |
| 10 mM | 0.2842 mL | 1.4208 mL | 2.8416 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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