| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
DC50 for degrading ALK: 10 and 180 nM[1]
TL13-12 targets anaplastic lymphoma kinase (ALK) for degradation via the ubiquitin-proteasome pathway. It inhibits ALK activity with an IC50 of 0.69 nM. In addition to ALK, TL13-12 also prompts the degradation of additional kinases including Aurora A (IC50 = 13.5 nM), FER (IC50 = 5.74 nM), PTK2 (IC50 = 18.4 nM), and RPS6KA1 (IC50 = 65 nM). |
|---|---|
| ln Vitro |
ALK can be selectively degraded by TL13-12 (0-200 nM; 16 hours), with DC50s of 10 nM and 180 nM in H3122 cell and Karpas 299, respectively[1]. In Kelly and CHLA20 cells, TL13-12 (0-160 nM; 16 hours) decreases the expression of the ALK and aurora A proteins in a dose-dependent manner[1]. In CHLA20 cells, TL13-12 (100 nM; 16 hours) dramatically suppresses Tariqudan-induced ALK and Aurora A protein expression[1].
TL13-12 is a potent ALK-PROTAC degrader with an IC50 of 0.69 nM for ALK inhibition. It degrades ALK in cells with DC50 values of 10 nM in H3122 cells and 180 nM in Karpas 299 cells. TL13-12 (0-200 nM; 16 hours) is selective for degradation of ALK. It also degrades ALK and Aurora A protein expression in a dose-dependent manner in Kelly and CHLA20 cells. |
| ln Vivo |
Specific in vivo activity data for TL13-12 are not detailed in the available sources. As a potent and selective ALK-PROTAC degrader with demonstrated cellular activity, the compound is expected to have in vivo efficacy in ALK-driven tumor models. PROTAC degraders offer the potential for sustained target inhibition and improved therapeutic outcomes. Further in vivo studies are warranted to confirm its anti-tumor activity.
|
| Enzyme Assay |
The ALK binding and degradation assay for TL13-12 involves measuring the compound's ability to inhibit ALK kinase activity and induce ALK protein degradation. Kinase inhibition is assessed using a recombinant ALK kinase assay with ATP and a peptide substrate. Degradation is evaluated by treating cells with TL13-12 and measuring ALK protein levels by Western blot. DC50 values (concentration for 50% degradation) are calculated from dose-response curves.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: Kelly and CHLA20 cells Tested Concentrations: 0 nM; 20 nM; 40 nM; 60 nM; 80 nM; 100 nM; 140 nM; 160 nM Incubation Duration: 16 hrs (hours) Experimental Results: demonstrated degrader behavior in cells. Western Blot Analysis[1] Cell Types: CHLA20 cells Tested Concentrations: 100 nM Incubation Duration: 16 hrs (hours) Experimental Results: diminished ALK and Aurora A protein expression. To evaluate the cellular activity of TL13-12, ALK-dependent cancer cell lines (such as H3122 and Karpas 299 cells) are seeded in 96-well plates and treated with varying concentrations of TL13-12 for 16 hours. ALK protein levels are assessed by Western blot analysis to determine the DC50 for degradation. Cell proliferation and viability are measured using MTT or CellTiter-Glo assays. The compound's effect on downstream signaling (such as STAT3 and ERK phosphorylation) can also be assessed. |
| Animal Protocol |
Specific in vivo animal experiment protocols for TL13-12 are not detailed in the available sources. As a PROTAC degrader, the compound would typically be evaluated in xenograft models using ALK-driven human cancer cell lines implanted subcutaneously into immunodeficient mice. TL13-12 would be administered intraperitoneally or intravenously, and tumor growth inhibition and ALK degradation in tumor tissue would be measured.
|
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for TL13-12 are not provided in the available sources. The compound has a molecular weight of 961.48 and a molecular formula of C45H53ClN10O10S. It is supplied as a solid powder with a purity of ≥98%. It should be stored dry, in the dark, at -20°C for up to 1 year. Stock solutions can be stored at 0-4°C for up to 1 month.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for TL13-12 are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent PROTAC degrader targeting ALK and other kinases, and its toxicity profile would be expected to reflect its mechanism of action. Standard safety precautions should be followed when handling this compound.
|
| References | |
| Additional Infomation |
TL13-12 is a potent and selective ALK-PROTAC degrader. It consists of the conjugation of TAE684 (an ALK inhibitor) and the cereblon ligand Pomalidomide. The compound inhibits ALK activity with an IC50 of 0.69 nM and degrades ALK with DC50 values of 10 nM and 180 nM in H3122 and Karpas 299 cells, respectively. It is supplied for research purposes.
|
| Molecular Formula |
C45H53CLN10O10S
|
|---|---|
| Molecular Weight |
961.481327772141
|
| Exact Mass |
960.335
|
| CAS # |
2229037-04-9
|
| PubChem CID |
138108740
|
| Appearance |
Yellow to brown solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.639
|
| LogP |
1.06
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
17
|
| Rotatable Bond Count |
21
|
| Heavy Atom Count |
67
|
| Complexity |
1810
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCN(CC4)CCOCCOCCNC(=O)CNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)OC
|
| InChi Key |
WXNUIPVZMJMPNM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C45H53ClN10O10S/c1-28(2)67(62,63)37-10-5-4-8-33(37)50-41-31(46)26-49-45(53-41)51-32-12-11-29(25-36(32)64-3)55-18-16-54(17-19-55)20-22-66-24-23-65-21-15-47-39(58)27-48-34-9-6-7-30-40(34)44(61)56(43(30)60)35-13-14-38(57)52-42(35)59/h4-12,25-26,28,35,48H,13-24,27H2,1-3H3,(H,47,58)(H,52,57,59)(H2,49,50,51,53)
|
| Chemical Name |
N-[2-[2-[2-[4-[4-[[5-Chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperazin-1-yl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetamide
|
| Synonyms |
TL-1312; TL13-12; TL1312; TL13 12;
|
| 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 (~104.01 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 | 1.0401 mL | 5.2003 mL | 10.4006 mL | |
| 5 mM | 0.2080 mL | 1.0401 mL | 2.0801 mL | |
| 10 mM | 0.1040 mL | 0.5200 mL | 1.0401 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.
 J Med Chem.2018 May 10;61(9):4249-4255. |
|---|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA