| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Ki: 190 pM (MERTK) IC50: 0.9 nM (MERTK)[1]
UNC5293 targets MERTK (MER receptor tyrosine kinase), a member of the TAM receptor family (MERTK, AXL, TYRO3). It is highly selective for MERTK over Axl, Tyro3, and Flt3. With an IC50 of 0.9 nM and Ki of 190 pM, it is among the most potent MERTK inhibitors reported. |
|---|---|
| ln Vitro |
UNC5293 offers targeted inhibition that is selective in cell-based experiments. UNC5293 inhibits MERTK phosphorylation in human B-cell acute lymphoblastic leukemia (B-ALL) cell line cultures, with an IC50 of 9.4 nM. UNC5293 has an IC50 of 170 nM, making it less effective against FLT3 in the SEM B-ALL cell line[1].
UNC5293 (compound 1) inhibits MERTK (IC50 = 0.9 nM, Ki = 190 pM) and is highly selective for Axl, Tyro3, and Flt3. In the human B-cell acute lymphoblastic leukemia (B-ALL) cell line, UNC5293 inhibits phosphorylation of MERTK with an IC50 of 9.4 nM. In the SEM B-ALL cell line, it also demonstrates cellular target engagement. |
| ln Vivo |
In orthotopic 697 B-ALL mouse xenografts, UNC5293 (oral administration; 120 mg/kg; single dosage) efficiently suppresses MERTK in vivo[1]. With a 7.8-hour half-life and 58% oral bioavailability, UNC5293 (oral gavage; 3 mg/kg; single dose) exhibits excellent mouse PK characteristics. Its Cmax and AUClast are 9.2 μM and 2.5 h*μM, respectively[1].
No in vivo efficacy data is detailed in the provided references, though UNC5293 exhibits excellent mouse pharmacokinetic properties and is reported for bone marrow leukemia research. Based on its potent MERTK inhibition and favorable PK profile, it is expected to show efficacy in mouse models of acute myeloid leukemia (AML) or B-ALL. |
| Enzyme Assay |
A biochemical MERTK inhibition assay is performed using purified recombinant MERTK kinase domain. Increasing concentrations of UNC5293 (0.01 nM to 1 uM) are incubated with the enzyme, ATP, and a peptide substrate. A time-resolved fluorescence resonance energy transfer (TR-FRET) or radiometric detection method is used to calculate the IC50 of 0.9 nM and Ki of 190 pM. Selectivity is assessed using a panel of 30+ additional kinases.
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| Cell Assay |
For cellular MERTK phosphorylation assays, B-ALL cell lines (e.g., SEM, RS4;11) are seeded and treated with increasing concentrations of UNC5293 (0.1-1000 nM) for 1-2 hours. Cells are lysed, and MERTK autophosphorylation is detected by Western blot using a phospho-MERTK-specific antibody. The IC50 for inhibiting cellular MERTK phosphorylation is determined (e.g., 9.4 nM in SEM cells). Cell viability is assessed after 72 hours of treatment using CellTiter-Glo.
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| Animal Protocol |
UNC5293 exhibits excellent mouse pharmacokinetic properties with good oral bioavailability. It is typically administered to mice via oral gavage at doses determined from PK studies. In bone marrow leukemia mouse models (e.g., xenografts of B-ALL cells), tumor burden and leukemia progression are monitored.
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| ADME/Pharmacokinetics |
UNC5293 exhibits excellent mouse pharmacokinetic properties, including good oral bioavailability and a favorable half-life. Detailed PK parameters (Cmax, AUC, T1/2) are not specified in the provided references.
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| Toxicity/Toxicokinetics |
No specific toxicology data is reported for UNC5293. The high selectivity of UNC5293 for MERTK over other kinases (Axl, Tyro3, Flt3) suggests a potentially favorable safety profile with fewer off-target liabilities.
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| References | |
| Additional Infomation |
UNC5293 (CAS: 2226789-82-6) is a potent, highly selective, orally available inhibitor of MER receptor tyrosine kinase (MERTK) with IC50 = 0.9 nM and Ki = 190 pM. It inhibits MERTK phosphorylation in B-ALL cells (IC50 = 9.4 nM). UNC5293 exhibits excellent mouse PK properties and is used for bone marrow leukemia research. Molecular formula: C30H42N6O2; molecular weight: 518.69. High selectivity is maintained over Axl, Tyro3, and Flt3.
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| Molecular Formula |
C30H42N6O2
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|---|---|
| Molecular Weight |
518.69
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| Exact Mass |
518.336
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| CAS # |
2226789-82-6
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| PubChem CID |
146403042
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| Appearance |
Colorless to light yellow viscous liquid
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
758
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC[C@H](C)NC1=NC=C2C(=CN(C2=N1)C3CCC(CC3)O)C4CCN(CC4)C(=O)C5=CC(=NC(=C5)C)C
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| InChi Key |
MSWOWUREQODTRO-CCYWVKEMSA-N
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| InChi Code |
InChI=1S/C30H42N6O2/c1-5-6-19(2)33-30-31-17-26-27(18-36(28(26)34-30)24-7-9-25(37)10-8-24)22-11-13-35(14-12-22)29(38)23-15-20(3)32-21(4)16-23/h15-19,22,24-25,37H,5-14H2,1-4H3,(H,31,33,34)/t19-,24?,25?/m0/s1
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| Chemical Name |
(2,6-dimethylpyridin-4-yl)-[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methanone
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 100 mg/mL (192.79 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9279 mL | 9.6397 mL | 19.2793 mL | |
| 5 mM | 0.3856 mL | 1.9279 mL | 3.8559 mL | |
| 10 mM | 0.1928 mL | 0.9640 mL | 1.9279 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.
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