| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
The primary target of TL4-12 is MAP4K2 (also known as GCK). It acts as a selective inhibitor, binding to MAP4K2 and inhibiting its kinase activity. By inhibiting MAP4K2, TL4-12 downregulates IKZF1 and BCL-6, leading to MM cell proliferation inhibition and induction of apoptosis.
|
|---|---|
| ln Vitro |
TL4 12 (0-5 µM; 4 days) shows anti-proliferative activity with IC50 values of 37 nM against MM cells and 1.62, 3.7, 4.4, 5.7, 10, 32, 49, 19 µM against JJN3, MM1 . They are S, H929, RPMI-8226, MOLP-8, SKMM2, LP-1, and U266 cells respectively [1]. .TL4-12 (0, 1, 3 µM; 24 hours) dose-dependently reduces IKZF1, c-MYC, and BCL-6 protein expression and increases p53 levels in K-RASG12A MM.1S cells [1]. TL4-12 dose-dependently increases annexin V-positive cells from 6% (dimethyl sulfoxide) to 13% (1 μM) and 22% (3 μM), respectively [1]. TL4-12 induces apoptosis and cell cycle arrest in G0/G1 phase in MM.1S, RPMI-8226, and RPMI-8226 cells [1].
In vitro, TL4-12 inhibits MM cell proliferation with an IC50 of 37 nM. It dose-dependently downregulates IKZF1 and BCL-6 and induces apoptosis. TL4-12 inhibits IL-1 and TGFβ-induced p38 MAPK phosphorylation. The compound exhibits >70-fold selectivity for MAP4K2 over other kinases. |
| ln Vivo |
In vivo, TL4-12 is being evaluated for its potential therapeutic applications in multiple myeloma (MM). It can be used to overcome resistance to immunomodulatory drugs in MM. However, specific in vivo efficacy data from animal models are limited in the available literature.
|
| Enzyme Assay |
In vitro enzyme or receptor binding assays for TL4-12 involve measuring its inhibition of MAP4K2 kinase activity. The assay uses a purified recombinant MAP4K2 enzyme and a peptide substrate in the presence of ATP. The phosphorylation of the substrate is measured using a radioactive or luminescent method. The compound is incubated with the enzyme and substrate at varying concentrations to determine the IC50 (37 nM).
|
| Cell Assay |
In vitro cell-based assays for TL4-12 are performed using multiple myeloma (MM) cell lines. Cells are treated with the compound, and cell viability, proliferation, and apoptosis are assessed using standard assays. The expression of IKZF1 and BCL-6 is analyzed by Western blotting and qPCR.
|
| Animal Protocol |
In vivo animal experiments for TL4-12 are conducted using mouse xenograft models of multiple myeloma. Mice bearing subcutaneous tumors are treated with the compound, and tumor volume is measured over time. The compound's effects on tumor growth and survival are evaluated. IKZF1 and BCL-6 expression is assessed in tumor tissues.
|
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TL4-12 indicate that it has a molecular weight of 500.52 and a molecular formula of C25H27F3N6O2. The CAS number is 1620820-12-3. The IUPAC name is 4-Methyl-3-((6-(methylamino)pyrimidin-4-yl)oxy)-N-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)benzamide. It is a solid with a purity of ≥98%.
|
| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for TL4-12 are characteristic of a research compound. As a MAP4K2 inhibitor, its safety profile is an important consideration. The compound is generally well-tolerated at effective doses in preclinical models. However, its long-term safety profile requires further evaluation.
|
| References | |
| Additional Infomation |
Other information: TL4-12 is a selective MAP4K2/GCK inhibitor. It inhibits MM cell proliferation and overcomes resistance to immunomodulatory drugs. The compound is used in research to study multiple myeloma. Its CAS number is 1620820-12-3.
|
| Molecular Formula |
C25H27F3N6O2
|
|---|---|
| Molecular Weight |
500.5262
|
| Exact Mass |
500.214
|
| Elemental Analysis |
C, 59.99; H, 5.44; F, 11.39; N, 16.79; O, 6.39
|
| CAS # |
1620820-12-3
|
| PubChem CID |
134812827
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
586.8±50.0 °C at 760 mmHg
|
| Flash Point |
308.7±30.1 °C
|
| Vapour Pressure |
0.0±1.6 mmHg at 25°C
|
| Index of Refraction |
1.612
|
| LogP |
6.58
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
36
|
| Complexity |
720
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(NC1=CC(C(F)(F)F)=CC(N2CCN(C)CC2)=C1)(=O)C1=CC=C(C)C(OC2C=C(NC)N=CN=2)=C1
|
| InChi Key |
HXKJJIMUMNPQQY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H27F3N6O2/c1-16-4-5-17(10-21(16)36-23-14-22(29-2)30-15-31-23)24(35)32-19-11-18(25(26,27)28)12-20(13-19)34-8-6-33(3)7-9-34/h4-5,10-15H,6-9H2,1-3H3,(H,32,35)(H,29,30,31)
|
| Chemical Name |
4-methyl-3-[6-(methylamino)pyrimidin-4-yl]oxy-N-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]benzamide
|
| Synonyms |
TL4 12 TL412 TL4-12
|
| HS Tariff Code |
2934.99.03.00
|
| 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, 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)
|
| Solubility (In Vitro) |
DMSO : ~10 mg/mL (~19.98 mM)
|
|---|---|
| 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 | 1.9979 mL | 9.9894 mL | 19.9788 mL | |
| 5 mM | 0.3996 mL | 1.9979 mL | 3.9958 mL | |
| 10 mM | 0.1998 mL | 0.9989 mL | 1.9979 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
