| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
Thrombopoietin receptor (TPO receptor/c-Mpl). TPO-Agonist-1 is a potent and selective thrombopoietin (TPO) receptor agonist that activates MPL signaling to promote megakaryocyte proliferation and platelet production.
|
|---|---|
| ln Vitro |
In vitro, TPO-Agonist-1 activates the thrombopoietin receptor (c-Mpl), mimicking the activity of endogenous thrombopoietin. This activation promotes megakaryocyte proliferation and differentiation, leading to increased platelet production. The compound is a small molecule mimetic of TPO with potent agonist activity.
|
| ln Vivo |
By interacting with TPO receptors on megakaryocytes, thrombopoietin (TPO) receptor agonists are novel therapies for patients with chronic ITP. These therapies can increase platelet counts, decrease bleeding events, and lessen the need for auxiliary or rescue treatment. Although TPO receptor agonists are well tolerated, there is still some confusion surrounding the possibility of myelofibrosis and thrombosis [2].
In vivo, TPO-Agonist-1 interacts with TPO receptors on megakaryocytes to increase platelet counts, decrease bleeding events, and reduce the need for adjunctive or rescue treatments. It is used as a promoter of platelet production and megakaryopoiesis in models of thrombocytopenia. TPO receptor agonists are novel therapies for patients with chronic immune thrombocytopenia (ITP). |
| Enzyme Assay |
Non-cell receptor binding assays are performed using membrane preparations from cells expressing the human thrombopoietin receptor (c-Mpl). Radioligand binding studies are conducted using [¹²⁵I]-labeled TPO or a suitable radiolabeled small molecule tracer. Membranes are incubated with the radioligand and varying concentrations of TPO-Agonist-1 (0.001-100 μM). Nonspecific binding is determined with excess unlabeled TPO or a reference compound. After incubation, filtration and scintillation counting are performed. Ki values are calculated from competition curves.
|
| Cell Assay |
Cellular assays are performed using cell lines expressing the TPO receptor (e.g., UT-7/TPO or Ba/F3 cells). Cells are treated with TPO-Agonist-1 at concentrations ranging from 0.01 nM to 100 μM. Proliferation is measured using MTT or CellTiter-Glo assays. STAT5 phosphorylation is assessed by Western blotting or phospho-flow cytometry as a measure of receptor activation. EC₅₀ values are calculated from dose-response curves.
|
| Animal Protocol |
In vivo studies are conducted in animal models of thrombocytopenia, including chemotherapy-induced or immune-mediated thrombocytopenia. TPO-Agonist-1 is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Platelet counts are measured in peripheral blood at various time points. Megakaryocyte numbers in bone marrow are assessed by histology. Efficacy is evaluated by monitoring bleeding time and platelet recovery.
|
| ADME/Pharmacokinetics |
TPO-Agonist-1 is orally active with good bioavailability. The compound has a molecular weight of 466.5 g/mol and a molecular formula of C25H22N8O2. It is a small molecule TPO mimetic. Further pharmacokinetic parameters such as half-life, clearance, and protein binding would be required for therapeutic development. The compound is typically used in research settings.
|
| Toxicity/Toxicokinetics |
TPO receptor agonists such as TPO-Agonist-1 are generally well tolerated, but there is some confusion surrounding the possibility of myelofibrosis and thrombosis. Comprehensive toxicology data for TPO-Agonist-1 are limited to research use. Standard safety pharmacology studies would be required for clinical development. The compound is for research use only.
|
| References |
|
| Additional Infomation |
SB-559448 is a small molecule drug that mimics the activity of thrombopoietin (TPO), a protein factor that promotes platelet growth and production. Developed by GlaxoSmithKline, this drug is used to treat thrombocytopenia. Thrombocytopenia (a low platelet count) is a common side effect of many chemotherapy drugs, leading to uncontrollable bleeding and thus a significant problem in cancer patient treatment.
Drug Indications Studied for the treatment of thrombocytopenia. TPO-Agonist-1 (SB-559448) is a small molecule drug that mimics the activity of thrombopoietin (TPO), a protein factor that promotes platelet growth and production. It was developed by GlaxoSmithKline for the treatment of thrombocytopenia. Thrombocytopenia (a low platelet count) is a common side effect of many chemotherapy drugs, leading to uncontrollable bleeding. The compound is not approved for clinical use and is available for research purposes only. |
| Molecular Formula |
C25H22N8O2
|
|---|---|
| Molecular Weight |
466.5
|
| Exact Mass |
466.186
|
| CAS # |
1033040-23-1
|
| PubChem CID |
135451068
|
| Appearance |
Pink to red solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
703.5±70.0 °C at 760 mmHg
|
| Flash Point |
379.3±35.7 °C
|
| Vapour Pressure |
0.0±2.3 mmHg at 25°C
|
| Index of Refraction |
1.735
|
| LogP |
3.28
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
834
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)N=NC3=CC=CC(=C3O)C4=CC(=CC=C4)C5=NNN=N5)C
|
| InChi Key |
YLSNQYHZCMCURB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H22N8O2/c1-14-10-11-19(12-15(14)2)33-25(35)22(16(3)30-33)27-26-21-9-5-8-20(23(21)34)17-6-4-7-18(13-17)24-28-31-32-29-24/h4-13,30,34H,1-3H3,(H,28,29,31,32)
|
| Chemical Name |
2-(3,4-dimethylphenyl)-4-[[2-hydroxy-3-[3-(2H-tetrazol-5-yl)phenyl]phenyl]diazenyl]-5-methyl-1H-pyrazol-3-one
|
| Synonyms |
TPOAgonist1; TPO Agonist 1; TPO-Agonist-1
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 36 mg/mL (~77.17 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.29 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 20.0 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 mg/mL (4.29 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1436 mL | 10.7181 mL | 21.4362 mL | |
| 5 mM | 0.4287 mL | 2.1436 mL | 4.2872 mL | |
| 10 mM | 0.2144 mL | 1.0718 mL | 2.1436 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00621894
Conditions:Immune Thrombocytopenic PurpuraProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
