| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
Purity: ≥98%
TL13-12 is novel, potent and selective PROTAC degrader of anaplastic lymphoma kinase (ALK) with potential anticancer activity. It degrades ALK with DC50 values of 10 and 180 nM in H3122 and Karpas 299 cells, respectively. It comprises the cereblon E3 ligase ligand Pomalidomide conjugated to an ALK inhibitor. TL13-12 is the first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB) cell lines. TL13-12 was developed through conjugation of known pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand pomalidomide. In some cell types, the degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).
| Targets |
|
|
|---|---|---|
| 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].
|
|
| 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. |
|
| References |
| 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
|
| 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