| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
TWS119, a pyrrolopyrimidine compound, is a novel, potent and selective/specific GSK-3β (Glycogen synthase kinase-3β) inhibitor with potential usefulness for in vivo stem cell biology and therapy. It is capable of inducing neuronal differentiation and might be helpful for stem cell biology. It inhibits GSK-3β with an IC50 of 30 nM in a cell-free assay. When using mouse P19 EC cells, it is screened out of a library of pyrrolopyrimidines as a substance that selectively induces neuronal differentiation. TWS119 has a Kd value of 126 nM and strongly binds to GSK-3β. Combining TWS119 and GSK-3β modifies the complex's activity and causes subsequent transcriptional events that result in the induction of neurons. Additionally, TWS119 promotes neuronal differentiation of mESCs via a different mechanism as opposed to the conventional Wnt signaling pathway.
| Targets |
GSK-3β (IC50 = 30 nM)
|
|---|---|
| ln Vitro |
Treatment of a monolayer of P19 cells with 1 μM TWS119 causes 30–40% cells to differentiate specifically into neuronal lineages based on counting of TuJ1 positive cells with correct neuronal morphology (up to 60% neuronal differentiation occurred through the standard EB formation protocol with concomitant TWS119 treatment). Surface plasmon resonance (SPR) measurements of TWS119's strong GSK-3-binding affinity (K D = 126 nM) and IC50 of 30 nM further support this conclusion. [1] WS119 is found to potently induces neuronal differentiation in both mouse embryonal carcinoma and ES cells. [2] TWS119 treatment towards hepatic stellate cells (HSC) leads to reduced b-catenin phosphorylation, induces nuclear translocation of b-catenin, elevates glutamine synthetase production, impedes synthesis of smooth muscle actin and Wnt5a, but promotes the expression of glial fibrillary acidic protein, Wnt10b, and paired-like homeodomain transcription factor 2c.[3] TWS119 causes a sharp up-regulation of the expression of Tcf7, Lef1, and other Wnt target genes like Jun, Ezd7 (encoding Frizzled-7), and Nlk (encoding Nemo-like kinase) in addition to triggering a rapid accumulation of -catenin (mean 6.8-fold increase by densitometry). TWS119 causes a dose-dependent reduction in T cell-specific killing and IFN-g release along with the maintenance of IL-2 production.[4] In polyclonally activated human T cells, treatment with TWS119 induces Wnt signaling, according to a recent study. Unlike control-activated T cells, which develop a CD45RO(+)CD62L(-) effector phenotype in a TWS119 dose-dependent manner, these T cells maintain a native CD45RA(+)CD62L(+) phenotype. Because cell division is prevented by TWS119-induced Wnt signaling, T cell expansion is reduced. Additionally, degranulation and IFN- production in response to T cell activation—which are both indicators of T cell effector function—are impaired. The inability of TWS119-treated T cells to use autocrine IL-2 for expansion may be the cause of the block in T cell division. This is because TWS119 treatment reduces the expression of the IL-2R. [5]
|
| ln Vivo |
A cell population that expressed low levels of CD44 and high levels of CD62L on the cell surface when 30 mg/kg of TWS119 is administered.[4]
|
| Cell Assay |
All rats are divided into four groups at random as follows: Sham group rats undergo the same surgical procedure, but the filament is not inserted, and they are given 1 mL of dimethyl sulfoxide (1% DMSO in saline); After MCAO, the rats in the vehicle group receive 1 mL of DMSO. At 4 hours after MCAO, the rats in the rtPA group receive rtPA (10 mg/kg, Actilyse®). At 4 hours after MCAO, the rats in the rtPA+TWS119 group receive intraperitoneal TWS119 (30 mg/kg, dissolved in 1 mL 1% DMSO).
|
| Animal Protocol |
All rats are divided into four groups at random as follows: Sham group rats undergo the same surgical procedure, but the filament is not inserted, and they are given 1 mL of dimethyl sulfoxide (1% DMSO in saline); After MCAO, the rats in the vehicle group receive 1 mL of DMSO. At 4 hours after MCAO, the rats in the rtPA group receive rtPA (10 mg/kg, Actilyse®). At 4 hours after MCAO, the rats in the rtPA+TWS119 group receive intraperitoneal TWS119 (30 mg/kg, dissolved in 1 mL 1% DMSO).
|
| References | |
| Additional Infomation |
3-[[6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenol is a member of pyrroles.
|
| Molecular Formula |
C18H14N4O2
|
|---|---|
| Molecular Weight |
318.3294
|
| Exact Mass |
318.111
|
| Elemental Analysis |
C, 67.92; H, 4.43; N, 17.60; O, 10.05
|
| CAS # |
601514-19-6
|
| Related CAS # |
TWS119 TFA;1507095-58-0
|
| PubChem CID |
9549289
|
| Appearance |
Off-white to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
646.0±55.0 °C at 760 mmHg
|
| Flash Point |
344.5±31.5 °C
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
| Index of Refraction |
1.753
|
| LogP |
3.54
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
24
|
| Complexity |
424
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C1=C([H])C([H])=C([H])C(=C1[H])O[H])C1C2C([H])=C(C3C([H])=C([H])C([H])=C(C=3[H])N([H])[H])N([H])C=2N=C([H])N=1
|
| InChi Key |
VPVLEBIVXZSOMQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H14N4O2/c19-12-4-1-3-11(7-12)16-9-15-17(22-16)20-10-21-18(15)24-14-6-2-5-13(23)8-14/h1-10,23H,19H2,(H,20,21,22)
|
| Chemical Name |
3-((6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)phenol
|
| Synonyms |
TWS-119; TWS 119; TWS119
|
| 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: ~64 mg/mL (201.0 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.85 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 (7.85 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: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1414 mL | 15.7070 mL | 31.4139 mL | |
| 5 mM | 0.6283 mL | 3.1414 mL | 6.2828 mL | |
| 10 mM | 0.3141 mL | 1.5707 mL | 3.1414 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.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01087294 | Active Recruiting |
Procedure: Allogeneic stem cell transplant Procedure: Leukapheresis |
Leukemia, B-cell Lymphoma, Hodgkins |
National Cancer Institute (NCI) |
August 4, 2010 | Phase 1 |
TWS119 activates Wnt signaling in CD8+ T cells. Nat Med. 2009 Jul;15(7):808-13. |
Wnt signaling inhibits CD8+ T cell proliferation and effector differentiation |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
