| Size | Price | |
|---|---|---|
| 10mg | ||
| 25mg | ||
| 50mg | ||
| 100mg | ||
| 250mg |
Purity: ≥98%
TBK1 PROTAC 1 is a novel, potent and selective TBK1 PROTAC with DC50 of 12nM that selectively degrades TBK1 with excellent selectivity against a related kinase IKKε; It is a chemical tool to assess TBK1 as a target in mutant K-Ras cancer cells. Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that recruit an E3 ligase to a target protein to facilitate ubiquitination and subsequent degradation of that protein. While the field of targeted degraders is still relatively young, the potential for this modality to become a differentiated and therapeutic reality is strong, such that both academic and pharmaceutical institutions are now entering this interesting area of research. In this article, we describe a broadly applicable process for identifying degrader hits based on the serine/threonine kinase TANK-binding kinase 1 (TBK1) and have generalized the key structural elements associated with degradation activities. TBK1 PROTAC 1 is a potent hit (TBK1 DC50 = 12 nM, Dmax = 96%) with excellent selectivity against a related kinase IKKε, which was further used as a chemical tool to assess TBK1 as a target in mutant K-Ras cancer cells.
| ln Vitro |
VHL ligand 2 (10 μM) or the proteasome inhibitor Carfilzomib (100 nM) can both block TBK1 degradation mediated by PROTAC TBK1 degrader-2 (compound 3i) [1]. With an IC50 of 1.3 nM and 8.7 nM, respectively, PROTAC TBK1 degrader-2 (0-3 μM) shows poor selectivity between TBK1 and IKKε; nevertheless, at concentrations more than 50 times higher than the DC50 for TBK1, IKKε levels show no effect[1]. In K-Ras mutant and wild-type cells, PROTAC TBK1 degrader-2 (100 nM; 300 M; 72 h) is not synthetically lethal [1].
|
|---|---|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: K-Ras mutant cell lines (H23, A549, and H1792) and K-Rras wild type cell lines (H2110 and HCC827) Tested Concentrations: 100 nM, 300 nM Incubation Duration: 72 hrs (hours) Experimental Results: Lacked synthetically lethality in K-Ras mutant versus wild type cells. |
| References |
[1]. Crew AP, et al. Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1. J Med Chem. 2018 Jan 25;61(2):583-598.
|
| Molecular Formula |
C53H74BRN9O9S
|
|---|---|
| Molecular Weight |
1093.17857122421
|
| CAS # |
2052306-13-3
|
| SMILES |
BrC1=CN=C(NC2C=CC(=CC=2)OCCCOCCCCOCCCOCC(N[C@@H](C(N2C[C@H](C[C@@H]2C(NCC2C=CC(C3=C(C)N=CS3)=CC=2)=O)O)=O)C(C)(C)C)=O)N=C1NCCCN(C)C(C1CCC1)=O
|
| Chemical Name |
(2S,4R)-1-((S)-18-(4-((5-bromo-4-((3-(N-methylcyclobutanecarboxamido)propyl)amino)pyrimidin-2-yl)amino)phenoxy)-2-(tert-butyl)-4-oxo-6,10,15-trioxa-3-azaoctadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
|
| Synonyms |
TBK1 PROTAC-1; TBK1 PROTAC1; TBK1 PROTAC 1
|
| 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 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 | 0.9148 mL | 4.5738 mL | 9.1476 mL | |
| 5 mM | 0.1830 mL | 0.9148 mL | 1.8295 mL | |
| 10 mM | 0.0915 mL | 0.4574 mL | 0.9148 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 Jan 25;61(2):583-598. |
|---|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA