| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
TCEP[1][2]
PB1 acts as a reducing agent that targets and reduces intracellular disulfide bonds within proteins. By reducing these bonds, it activates the pro-survival ERK1/2 signaling pathway via activation of the BDNF effector. This pathway is critical for neuronal survival, particularly for retinal ganglion cells (RGCs). |
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| ln Vitro |
Strong activation of the BDNF effector ERK1/2 is produced by PB1. RGC survival is enhanced by PB1[1].
In vitro, PB1 produces a robust activation of the BDNF effector ERK1/2, promoting RGC survival. It increases retinal ganglion cell survival after axotomy (nerve cut) at extremely low concentrations, with efficacy observed in the nanomolar and picomolar concentration range (0.001-100 microM). |
| ln Vivo |
In experimental glaucoma, PB1 (150 μM; intraocular injection; 1 week) attenuates the loss of both RGC (retinal ganglion cells) soma and axons[1]. In experimental glaucoma, PB1 shields the RGC soma. The biological activity in vivo is limited by a single dose of PB1. In experimental glaucoma, PB1 attenuates the loss of RGC axons as well as soma. It takes 72 hours for PB1 (0.001~100 μM) to start saving acutely axotomized retinal ganglion cells[1][2].
In vivo, PB1 (150 microM; intraocular injection) attenuates the loss of both RGC soma and axons in an experimental glaucoma model over one week. It protects RGC soma and limits biological activity after a single dose, rescuing acutely axotomized retinal ganglion cells. |
| Enzyme Assay |
A non-cellular biochemical assay for PB1 involves measuring its reducing activity. Ellman's reagent (DTNB, 5,5′-dithio-bis-(2-nitrobenzoic acid)) is used. PB1 is added to a solution containing DTNB in a buffer (pH 8.0). The reduction of DTNB results in the formation of 2-nitro-5-thiobenzoate (TNB), which yields a yellow color. The absorbance is measured at 412 nm, and the concentration of free thiols is calculated using the Beer-Lambert law.
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| Cell Assay |
The primary in vitro cellular assay assesses neuronal survival. Primary retinal ganglion cell (RGC) cultures or RGC-5 cell lines are subjected to axotomy (simulated by cutting the cell‘s processes) or glutamate excitotoxicity to mimic glaucoma. Varying concentrations of PB1 (0.001 pM to 100 microM) are added to the culture media for 72 hours. Cell survival is quantified by counting live cells using fluorescent dyes (e.g., Calcein-AM) or an MTT assay for metabolic activity.
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| Animal Protocol |
Animal/Disease Models: SD (Sprague-Dawley) rats (180~ 200 g)[1]
Doses: 150 μM Route of Administration: Intraocular injection Experimental Results: PB1-treated eyes, 66% of RGCs survived at 1 week after axotomy. A well-established animal model for glaucoma is used. An experimental glaucoma model is induced in adult Sprague-Dawley rats, typically by injecting hypertonic saline into the episcleral veins to increase intraocular pressure (IOP) or by laser photocoagulation of the trabecular meshwork. PB1 (150 microM) is administered via a single intraocular injection (intravitreal injection, 5 microL). After 1 week, the rats are euthanized, and the retinas are dissected. RGC survival is measured by counting RGCs in retinal flat mounts labeled with a retrograde tracer (e.g., FluoroGold) or by using an RGC-specific antibody (e.g., Brn3a). |
| ADME/Pharmacokinetics |
PB1 is a borane-protected phosphine (C14H22BO4P, MW: 296.11). The borane protection is designed to enhance cell permeability. Once inside the cell, the borane group is likely removed, releasing the active TCEP analog. It is a liquid at room temperature. Its PK profile is not extensively characterized, but as a small molecule, it is expected to be rapidly distributed and excreted. A single intraocular dose provided effects lasting at least 1 week, suggesting a prolonged presence in the vitreous humor.
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| Toxicity/Toxicokinetics |
PB1 has been tested in preclinical models and shows no overt signs of general toxicity at effective doses. It is specifically designed to be neuroprotective. In vitro, it has a wide safety window, promoting cell survival at picomolar-nanomolar doses without cytotoxic effects up to 100 microM. No systemic toxicity or adverse events have been reported following intraocular injection in animal studies.
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| References |
[1]. Almasieh M, et al. A cell-permeable phosphine-borane complex delays retinal ganglion cell death after axonal injury through activation of the pro-survival extracellular signal-regulated kinases 1/2 pathway. J Neurochem. 2011;118(6):1075-1086.
[2]. Schlieve CR, et al. Synthesis and characterization of a novel class of reducing agents that are highly neuroprotective for retinal ganglion cells. Exp Eye Res. 2006;83(5):1252-1259. [3]. Niemuth NJ, et al. Intracellular disulfide reduction by phosphine-borane complexes: Mechanism of action for neuroprotection. Neurochem Int. 2016;99:24-32. |
| Additional Infomation |
PB1 is a borane-protected TCEP analog offering high cell permeability, stability, and the ability to form a high intracellular concentration gradient. It was developed by researchers at the Medical College of Wisconsin as a novel class of neuroprotective agents. It is a research-grade chemical and is not FDA-approved for any clinical indication.
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| Molecular Formula |
C14H22BO4P
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|---|---|
| Molecular Weight |
296.11
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| CAS # |
188714-28-5
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| Appearance |
Colorless to light yellow liquid
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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 (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (337.71 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.44 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.44 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3771 mL | 16.8856 mL | 33.7712 mL | |
| 5 mM | 0.6754 mL | 3.3771 mL | 6.7542 mL | |
| 10 mM | 0.3377 mL | 1.6886 mL | 3.3771 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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