PT109
Based on 1 Customer Validation
PT109 is an orally active, blood-brain barrier permeable multi-kinase inhibitor. By inhibiting PTBP1, PT109 promotes the switch of pyruvate kinase isoform from PKM2 to PKM1, thereby effectively inhibiting the proliferation and migration of glioblastoma multiforme and inducing its reprogramming into oligodendrocytes. PT109 also targets and regulates key signaling molecules such as JNK, SGK1, GSK3β to exert neuroprotective effects including promoting neurogenesis, inducing synapse formation and alleviating neuroinflammation. In Alzheimer's disease models, PT109 exhibits significant efficacy in improving spatial learning ability, along with excellent in vivo pharmacokinetic properties. PT109 can be used to investigate metabolic reprogramming of glioblastoma multiforme and neuroprotective mechanisms of Alzheimer's disease.
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- Pureté : 99.20%
- CAS No.: 2059104-90-2
- Formule: C23H31N3OS2
- Masse moléculaire:429.64
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
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JNK1 0.143 μM (IC50) |
JNK2 0.831 μM (IC50) |
JNK3 0.285 μM (IC50) |
SGK1 1.34 μM (IC50) |
SGK2 5.6 μM (IC50) |
SGK3 26.4 μM (IC50) |
ROCK2 34 μM (IC50) |
MMP-9 |
MMP-2 |
COX-2 |
iNOS |
PKM1 |
In Vitro
PT109 (10 μM; 24 h) significantly reduces the proportion of Ki67-positive (proliferative) human glioblastoma T98G and U251 cells[1].
PT109 (10-20 μM; 24 h, 72 h) reduces the proteolytic activity and protein expression of MMP-2 and MMP-9 in a dose-dependent manner in T98G and U251 human glioblastoma cells, downregulates the expression of stem cell, astrocyte and neuron markers, while upregulating the expression of oligodendrocyte markers (MBP, MOG), induces morphological changes in T98G, U251 and U87 human glioblastoma cells[1].
PT109 (10-20 μM; 72 h, 1-7 days) reduces the protein levels of PTBP1 and PKM2 in a dose- and time-dependent manner, while increasing the PKM1 level and the PKM1/PKM2 ratio, in human glioblastoma U251 cells, with the most significant effect observed at 20 μM for 7 days[1].
PT109 (10 μM; 3 d) promotes the differentiation of C17.2 mouse neural stem cells into cholinergic neurons, upregulates the expression of neurogenesis markers and cholinergic markers, and does not induce astrocyte differentiation[2].
PT109 (0.3-3 μM; 3 d) promotes synaptogenesis in primary rat hippocampal neurons and cortical neurons by upregulating the expression of the synaptogenesis marker Synapsin-1[2].
PT109 (100 μg/mL; 10 h) exhibits favorable blood-brain barrier permeability in the in vitro PAMPA-BBB assay, indicating its potential for central nervous system exposure[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:U251 human glioblastoma cell line
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Concentration:10, 20 μM (dose-response; 72 h); 20 μM (time-course; 1, 3, 7 days)
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Incubation Time:72 h; 1, 3, 7 days
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Result:Increased PKM1 protein levels and the PKM1/PKM2 ratio, and decreased PTBP1 and PKM2 protein levels, in a dose-dependent manner over 72 h. Decreased PTBP1 and PKM2 levels in a time-dependent manner, and increased PKM1 levels and the PKM1/PKM2 ratio in a time-dependent manner, over 7 days of treatment with 20 μM, with the most significant effects observed at 7 days (P<0.001 for PTBP1 reduction).
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Cell Line:C17.2 murine neural stem cells
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Concentration:10 μM
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Incubation Time:3 days
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Result:Increased the expression of Tuj-1 and MAP2 compared to vehicle control. Remarkably increased ChAT expression but showed no significant effect on GFAP expression relative to control.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:APP/PS1 mice with Alzheimer's disease (male, 3 months old at study start, B6C3 background, Alzheimer's disease transgenic model)[2]
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Dosage:30 mg/kg; 100 mg/kg
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Administration:oral; daily via diet; 3 or 6 months
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Result:Reduced Morris water maze escape latencies on day 5 (100 mg/kg, 6 months treatment).\n
Increased step-through test escape latency and reduced error frequency (100 mg/kg, 6 months treatment).\n
Significantly reduced number of activated microglia (Iba1-positive cells) and activated astrocytes (GFAP-positive cells) in brain cortex and hippocampus (30 mg/kg or 100 mg/kg, 3 or 6 months treatment).\nSignificantly reduced hippocampal levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 (30 mg/kg or 100 mg/kg, 6 months treatment).\n
Significantly reduced hippocampal levels of phosphorylated JNK (p-JNK) (30 mg/kg or 100 mg/kg, 6 months treatment).\n
Significantly reduced hippocampal and cortical levels of phosphorylated Tau (p-Tau, S396) (30 mg/kg or 100 mg/kg, 6 months treatment).
Chemical Information
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CAS No. 2059104-90-2
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Appearance Solid
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Masse moléculaire 429.64
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Formule C23H31N3OS2
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Color Light yellow to yellow
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SMILES
O=C(CCCCC1SSCC1)NC2CCC(CC2)NC3=CC=CC4=C3C=CN=C4
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (232.75 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.82 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.82 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
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Cell migration
Cell migration is a method that plays an important role in wound healing, cell differentiation, embryonic development, etc.
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SH-SY5Y neuronal-like differentiation
SH-SY5Y neuronal-like differentiation uses defined culture conditions to shift proliferative human neuroblastoma cells toward a neuron-like state, mainly assessed by reduced proliferation, neurite extension, neuronal-marker expression, and, in some protocols, increased dependence on neurotrophic support. Retinoic acid (RA) is commonly used for the first differentiation phase, and sequential RA followed by brain-derived neurotrophic factor (BDNF) in serum-free medium is a well-characterized approach for generating neuron-like SH-SY5Y cultures with extensive neurite outgrowth. The primary readouts are morphology-based neurite outgrowth and marker-based confirmation using proteins such as βIII-tubulin, MAP2, GAP43, synaptophysin, NeuN, NSE, TH, or related neuronal/synaptic markers, depending on the study endpoint.
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Protocol for Water Maze
The Morris Water Maze is a rodent spatial learning and memory assay in which a mouse or rat swims in opaque water to find an escape platform; in the hidden-platform version, the animal cannot see the platform and must use distal extra-maze cues to learn its fixed spatial location. The assay primarily measures hippocampus-dependent spatial learning during acquisition trials and spatial reference memory during probe trials after platform removal; readouts include escape latency, swim path length, swim speed, quadrant occupancy, platform-site crossings, and proximity to the former platform location.
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Cell differentiation
Cell differentiation refers to the process in which cells of the same origin gradually produce cell groups with different morphological structure and functional characteristics.
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Research Protocol for Neurological Diseases
PINK1/Parkin-mediated mitophagy pathway is a mitochondrial quality-control signaling axis in which mitochondrial depolarization stabilizes PINK1 on damaged mitochondria, activates Parkin recruitment and E3 ubiquitin ligase activity, promotes ubiquitination of outer mitochondrial membrane proteins, recruits selective autophagy adaptors, and drives lysosomal degradation of damaged mitochondria. In neurological disease research, this pathway is experimentally important because neurons, especially dopaminergic neurons, are highly dependent on mitochondrial integrity, and defective mitochondrial turnover can lead to mitochondrial dysfunction, oxidative stress, impaired neuronal survival, α-synuclein accumulation, and neuroinflammatory damage-associated signals. The genetic disease link is strongest in Parkinson’s disease because mutations in PRKN/parkin cause autosomal recessive juvenile parkinsonism, mutations in PINK1 cause hereditary early-onset Parkinson’s disease, and Drosophila studie
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Pureté et documentation
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Fiche technique (278 KB)
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SDS (251 KB)
- 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)
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Instruction de manipulation (2659 KB)
Références
[1]. Yang Y, et al. PT109, a novel multi-kinase inhibitor suppresses glioblastoma multiforme through cell reprogramming: Involvement of PTBP1/PKM1/2 pathway. Eur J Pharmacol. 2022;920:174837. [Content Brief]
[2]. Chen Q, et al. Discovery of a novel small molecule PT109 with multi-targeted effects against Alzheimer's disease in vitro and in vivo. Eur J Pharmacol. 2020;883:173361. [Content Brief]
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 |
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| DMSO | 1 mM | 2.3275 mL | 11.6376 mL | 23.2753 mL | 58.1882 mL |
| 5 mM | 0.4655 mL | 2.3275 mL | 4.6551 mL | 11.6376 mL | |
| 10 mM | 0.2328 mL | 1.1638 mL | 2.3275 mL | 5.8188 mL | |
| 15 mM | 0.1552 mL | 0.7758 mL | 1.5517 mL | 3.8792 mL | |
| 20 mM | 0.1164 mL | 0.5819 mL | 1.1638 mL | 2.9094 mL | |
| 25 mM | 0.0931 mL | 0.4655 mL | 0.9310 mL | 2.3275 mL | |
| 30 mM | 0.0776 mL | 0.3879 mL | 0.7758 mL | 1.9396 mL | |
| 40 mM | 0.0582 mL | 0.2909 mL | 0.5819 mL | 1.4547 mL | |
| 50 mM | 0.0466 mL | 0.2328 mL | 0.4655 mL | 1.1638 mL | |
| 60 mM | 0.0388 mL | 0.1940 mL | 0.3879 mL | 0.9698 mL | |
| 80 mM | 0.0291 mL | 0.1455 mL | 0.2909 mL | 0.7274 mL | |
| 100 mM | 0.0233 mL | 0.1164 mL | 0.2328 mL | 0.5819 mL |
PT109 Related Classifications
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