| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
|
|
|---|---|---|
| ln Vitro |
TL13-112 binds to cereblon with an IC50 of 2.4 uM.[1]. TL13-112 (0.01 μM-1 μM; 16 hours) selectively degrades ALK, with DC50s of 10 nM and 40 nM in H3122 cells and Karpas 299, respectively. ALK degradation occurs after four hours of treatment in H3122 cells and eight hours of therapy in Karpas 299 cells. The highest breakdown occurs after 16 hours in both cell lines. [1]. TL13-112 (0.01 μM-1 μM; 16 hours) reduces PTK2, ALK, FER, RPS6KA1, and Aurora A expression in H3122, Karpas 299, and Kelly cells in a dose-dependent manner [1].
In vitro, TL13-112 inhibits ALK activity with an IC50 of 0.14 nM. It shows degradation activity against ALK with DC50 values of 10 nM in H3122 cells and 40 nM in Karpas 299 cells. It dose-dependently inhibits proliferation of ALK-positive cell lines including H3122, Karpas 299, SU-DHL-1, Kelly, Lan5, SH-SY5Y, and CHLA20 cells. The compound exhibits selectivity, degrading only a handful of kinases (ALK, Aurora A, FER, PTK2, RPS6KA1). |
|
| ln Vivo |
No specific in vivo activity data is available for TL13-112. As a PROTAC degrader, it is expected to have in vivo efficacy in xenograft models of ALK-driven cancers, but published studies have not reported detailed in vivo results. The compound is primarily used as a tool for studying ALK degradation in cellular systems.
|
|
| Enzyme Assay |
For in vitro kinase inhibition assays (ALK): Recombinant ALK kinase (5-20 ng) is incubated with varying concentrations of TL13-112 (0.001-1000 nM) in kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 2 mM DTT, 0.01% Triton X-100). Add ATP (10-100 uM) and a peptide substrate (e.g., poly(Glu, Tyr) 4:1). Incubate at 30degC for 30-60 minutes. Measure phosphorylation using an anti-phosphotyrosine antibody in an ELISA or using a radiometric assay (33P-ATP). Calculate IC50.
|
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: H3122 and Karpas 299 cells Tested Concentrations: 0.01 μM; 0.05 μM; 0.1 μM; 0.5 μM; 1 μM Incubation Duration: 16 hrs (hours) Experimental Results: Inhibited ALK and Aurora A expression completely at 1 μM. Western Blot Analysis[1] Cell Types: H3122 and Karpas 299 cells Tested Concentrations: 0.01 μM; 0.05 μM; 0.1 μM; 0.5 μM; 1 μM Incubation Duration: 16 hrs (hours) Experimental Results: diminished PTK2, ALK, FER, RPS6KA1 and Aurora A expression. For degradation assays (Western blot): Culture ALK-positive cancer cells (H3122, Karpas 299, SU-DHL-1) in appropriate media. Treat cells with TL13-112 at concentrations ranging from 1 nM to 10 uM for 4-24 hours. For DC50 determination, treat with 0.1-1000 nM for 16-24 hours. Prepare whole cell lysates in RIPA buffer containing protease and phosphatase inhibitors. Run SDS-PAGE, transfer to nitrocellulose membranes, and blot with anti-ALK antibodies. Use anti-GAPDH or anti-beta-actin as loading controls. Quantify band intensity by densitometry. The DC50 is 10 nM in H3122 cells and 40 nM in Karpas 299 cells. For cell proliferation assays: Seed ALK-positive cells in 96-well plates (5,000-10,000 cells/well). Treat with TL13-112 at 0.01-10,000 nM for 72 hours. Measure viability by CellTiter-Glo or MTT assay. Calculate GI50 values. For time-course degradation experiments, treat cells with a fixed concentration (e.g., 100 nM) and harvest at 0, 1, 2, 4, 8, 12, and 24 hours. For ubiquitination assays, immunoprecipitate ALK from treated cell lysates and blot with anti-ubiquitin antibodies. |
|
| Animal Protocol |
No in vivo protocol is available. For potential xenograft studies: Subcutaneously inoculate immunodeficient mice with ALK-positive cancer cells (e.g., H3122, Karpas 299). When tumors reach ~150 mm3, administer TL13-112 intraperitoneally or intravenously at doses of 10-50 mg/kg. Formulate in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. Monitor tumor volume and body weight. Collect tumors for ALK degradation analysis by Western blot.
|
|
| ADME/Pharmacokinetics |
No pharmacokinetic data is available. TL13-112 has a molecular weight of 1001.39 (as free base) or 1002.6 g/mol. The compound has high molecular weight and complexity, which may impact oral bioavailability. It is soluble in DMSO. Standard DMSO-based formulations are used for in vitro studies. It should be stored as a powder at -20degC, protected from light and moisture.
|
|
| Toxicity/Toxicokinetics |
No toxicity data is available. As a PROTAC that recruits the cereblon E3 ligase, it may have off-target degradation effects similar to other cereblon-modulating drugs (e.g., thalidomide analogs). Handle with caution, especially if pregnant, due to the potential teratogenicity of the pomalidomide-derived moiety. Use appropriate personal protective equipment.
|
|
| References | ||
| Additional Infomation |
TL13-112 is a research-grade PROTAC compound for laboratory use only, not for human therapeutic applications. It is a valuable tool for studying ALK biology and for validating targeted protein degradation as a therapeutic strategy for ALK-driven cancers. The compound comprises the ALK inhibitor ceritinib linked to pomalidomide. Unlike traditional kinase inhibitors, PROTACs induce degradation of the target protein, potentially overcoming resistance mutations. No clinical trials or approved status exist for this research compound.
|
| Molecular Formula |
C₄₉H₆₀CLN₉O₁₀S
|
|---|---|
| Molecular Weight |
1002.57
|
| Exact Mass |
1001.387
|
| Elemental Analysis |
C, 58.70; H, 6.03; Cl, 3.54; N, 12.57; O, 15.96; S, 3.20
|
| CAS # |
2229037-19-6
|
| Related CAS # |
2229037-19-6;
|
| PubChem CID |
138108958
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.620
|
| LogP |
3.02
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
16
|
| Rotatable Bond Count |
22
|
| Heavy Atom Count |
70
|
| Complexity |
1890
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C=NC(=NC=1NC1C=CC=CC=1S(C(C)C)(=O)=O)NC1=CC(C)=C(C=C1OC(C)C)C1CCN(CCOCCOCCNC(CNC2=CC=CC3C(N(C(C=32)=O)C2C(NC(CC2)=O)=O)=O)=O)CC1
|
| InChi Key |
XIRQUXILNXIWDI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C49H60ClN9O10S/c1-29(2)69-40-26-34(31(5)25-38(40)55-49-53-27-35(50)45(57-49)54-36-10-6-7-12-41(36)70(65,66)30(3)4)32-15-18-58(19-16-32)20-22-68-24-23-67-21-17-51-43(61)28-52-37-11-8-9-33-44(37)48(64)59(47(33)63)39-13-14-42(60)56-46(39)62/h6-12,25-27,29-30,32,39,52H,13-24,28H2,1-5H3,(H,51,61)(H,56,60,62)(H2,53,54,55,57)
|
| Chemical Name |
N-[2-[2-[2-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-methyl-5-propan-2-yloxyphenyl]piperidin-1-yl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetamide
|
| Synonyms |
TL13112 TL13 112
|
| 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 : ~100 mg/mL (~99.74 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 | 0.9974 mL | 4.9872 mL | 9.9744 mL | |
| 5 mM | 0.1995 mL | 0.9974 mL | 1.9949 mL | |
| 10 mM | 0.0997 mL | 0.4987 mL | 0.9974 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
