TL13-112 (TL-13112; TL13 112) is a novel and potent PROTAC degrader of Anaplastic Lymphoma Kinase (ALK) by conjugation of LDK378 with pomalidomide.
Physicochemical Properties
| 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) |
Biological Activity
| 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]. | |
| 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. |
|
| References |
[1]. Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK).J Med Chem. 2018 May 10;61(9):4249-4255. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |