| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
UNC2541 is a novel, potent and selective Mer tyrosine kinase (MerTK) inhibitor which binds in the MerTK ATP pocket with an IC50 of 4.4 nM, and it is more selective over Axl, Tyro3 and Flt3. UNC2541 suppresses phosphorylated MerTK (pMerTK; 510 nM EC50). The cell-based ELISA demonstrates sub-micromolar inhibitory activity for UNC2541. Furthermore, it was demonstrated that these macrocycles bind in the MerTK ATP pocket by resolving the X-ray structure of the MerTK protein in complex with UNC2541. According to UNC2541, the IC50 values for MerTH, AXL, TYRO3, and FLT3 were 4.4 nM, 120 nM, and 320 nM, respectively.
| Targets |
MERTK (IC50 = 4.4 nM)
UNC2541 is a potent and specific inhibitor of Mer tyrosine kinase (MerTK). In a microfluidic capillary electrophoresis (MCE) enzymatic assay, its IC50 against MerTK is 4.4 ± 0.5 nM. It shows high selectivity over other TAM family kinases (Axl IC50 = 120 ± 60 nM, Tyro3 IC50 = 220 ± 8 nM) and FMS-like tyrosine kinase 3 (Flt3 IC50 = 2320 ± 110 nM), yielding a >500-fold selectivity window against Flt3. In a broader kinase panel of 30 kinases, at a concentration of 430 nM (100-fold above its MerTK IC50), UNC2541 inhibited five additional tyrosine kinases and three serine/threonine kinases by more than 50%. |
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| ln Vitro |
UNC2541 is an effective and highly selective inhibitor of Mer tyrosine kinase (MerTK), with an IC50 of 4.4 nM. It binds in the MerTK ATP pocket and is more selective than Axl (IC50, 120 nM), Tyro3 (IC50, 220 nM), and Flt3 (IC50, 320 nM). Phosphorylated MerTK (pMerTK; EC50, 510 nM) is inhibited by UNC2541[1]. UNC2541 inhibits MerTK that has been phosphorylated (pMerTK; EC50, 510 nM)[1].
UNC2541 demonstrated potent inhibitory activity in a cell-based ELISA assay measuring tyrosine phosphorylation of a chimeric EGFR-MerTK protein (pMerTK). The reported EC50 in this assay was 510 nM. Its inhibitory activity and selectivity profile were characterized through structure-activity relationship (SAR) studies focusing on macrocycle ring size and linker modifications. The binding mode was confirmed by X-ray crystallography, showing that UNC2541 binds to the ATP pocket of MerTK. |
| Enzyme Assay |
Enzymatic activity against MerTK, Axl, Tyro3, and Flt3 was assessed using an in-house microfluidic capillary electrophoresis (MCE) assay. The assay was performed at the respective Km ATP concentration for each kinase. Inhibitory concentrations (IC50) were determined from dose-response curves.
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| Cell Assay |
A cell-based enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inhibition of MerTK tyrosine phosphorylation in HEK293 cells. The cells were transfected with a cDNA encoding a chimeric protein consisting of the extracellular and transmembrane domains of the epidermal growth factor receptor (EGFR) fused to the intracellular kinase domain of MerTK. Kinase activity was stimulated by the addition of EGF. Compound activity was measured by quantifying the level of phosphorylated MerTK (pMerTK) using ELISA. The half-maximal effective concentration (EC50) was calculated from the dose-response curve.
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| References | |
| Additional Infomation |
UNC2541 (Compound 11) is a macrocyclic pyrimidine compound discovered using a structure-based drug design approach, with the aim of developing a MerTK-specific inhibitor. Its design objective was to improve selectivity for Flt3 compared to previous inhibitors, such as UNC2025. The X-ray co-crystal structure of MerTK with UNC2541 (PDB: 5K0X) confirmed the predicted ATP pocket binding mode, but also revealed that the orientation of the primary amine and carbonyl groups of the macrocycle relative to the R727, N728, and D741 residues was not as expected. The authors note that while UNC2541 exhibits good MerTK specificity in the TAM family and Flt3, its selectivity for other kinase families and cellular activity require further optimization before it can be used as a lead compound for subsequent studies.
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| Molecular Formula |
C24H34FN7O2
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|---|---|
| Molecular Weight |
471.570868015289
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| Exact Mass |
471.581
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| Elemental Analysis |
C, 61.13; H, 7.27; F, 4.03; N, 20.79; O, 6.79
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| CAS # |
1612782-86-1
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| Related CAS # |
1612782-86-1
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| PubChem CID |
74538669
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
34
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| Complexity |
618
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CCCNC2=NC=C(C(=N2)NCCCC[C@@H](C(=O)NCC1)N)C(=O)NCC3=CC=C(C=C3)F
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| InChi Key |
ONIHBIZGUJZDHG-FQEVSTJZSA-N
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| InChi Code |
InChI=1S/C24H34FN7O2/c25-18-10-8-17(9-11-18)15-30-22(33)19-16-31-24-29-14-5-2-1-4-13-28-23(34)20(26)7-3-6-12-27-21(19)32-24/h8-11,16,20H,1-7,12-15,26H2,(H,28,34)(H,30,33)(H2,27,29,31,32)/t20-/m0/s1
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| Chemical Name |
(7S)-7-amino-N-[(4-fluorophenyl)methyl]-8-oxo-2,9,16,18,21-pentazabicyclo[15.3.1]henicosa-1(21),17,19-triene-20-carboxamide
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| Synonyms |
UNC2541; UNC-2541; UNC 2541
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 10~94 mg/mL (21.2~199.3 mM)
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| 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 | 2.1206 mL | 10.6029 mL | 21.2058 mL | |
| 5 mM | 0.4241 mL | 2.1206 mL | 4.2412 mL | |
| 10 mM | 0.2121 mL | 1.0603 mL | 2.1206 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.
 a. Structure of1; b. X-ray crystal structure of1in complex with MerTK (kinase domain) (PDB ID code 4MHA); c. Structure of2; d. Docking model of macrocyclic pyrimidine2.ChemMedChem.2017 Feb 3;12(3):207-213. |
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 Kinase tree.ChemMedChem.2017 Feb 3;12(3):207-213. |
 a. Structure of11; b&C. X-ray crystal structure of11in complex with Mer (kinase domain) (PDB ID code 5K0X).ChemMedChem.2017 Feb 3;12(3):207-213. |
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