| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C27H27N5 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
URMC-099 is an orally bioavailable, potent inhibitor of mixed lineage kinase type 3 (MLK3) with an IC50 of 14 nM, and it shows excellent blood-brain barrier penetration properties. It is supplied as an off-white to yellow solid (C27H27N5, MW 421.54) at 98.69% purity.
Physical & Chemical Properties
| CAS Number | 1229582-33-5 |
|---|---|
| Molecular Formula | C27H27N5 |
| Molecular Weight | 421.54 g/mol |
| Purity | 98.69% |
| Appearance | Solid |
| Color | Off-white to yellow |
| SMILES | CN(CC1)CCN1CC(C=C2)=CC=C2C3=CN=C4C(C(C5=CC=C(NC=C6)C6=C5)=CN4)=C3 |
| Target | LRRK2, FLT3, FLT1, ABL1 (T315I), ABL1, SGK, SGK1, AurA, AurB, AurC, IKKβ, IKKα, TNFα, ROCK1, ROCK2, CDK1, CDK2, TRKA, c-MET, TRKB, IGF1R, LCK, MEKK2, SYK, AMPK, JNK1, SRC, ZAP70, ERK2, P38α, CYP3A4 |
| Signaling Pathway | MAPK/ERK Pathway; Autophagy |
| Solubility | In Vitro: DMSO: ≥ 33 mg/mL (78.28 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) * "≥" means soluble, but saturation unknown. |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 2 years; -20°C, 1 year. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
LRRK2 11 nM (IC50) |
FLT3 4 nM (IC50) |
FLT1 39 nM (IC50) |
ABL1 (T315I) 3 nM (IC50) |
ABL1 6.8 nM (IC50) |
SGK 67 nM (IC50) |
SGK1 201 nM (IC50) |
AurA 108 nM (IC50) |
AurB 123 nM (IC50) |
AurC 290 nM (IC50) |
IKKβ 257 nM (IC50) |
IKKα 591 nM (IC50) |
TNFα 460 nM (IC50) |
ROCK1 1030 nM (IC50) |
ROCK2 111 nM (IC50) |
CDK1 1125 nM (IC50) |
CDK2 1180 nM (IC50) |
TRKA 85 nM (IC50) |
c-MET 177 nM (IC50) |
TRKB 217 nM (IC50) |
IGF1R 307 nM (IC50) |
LCK 333 nM (IC50) |
MEKK2 661 nM (IC50) |
SYK 731 nM (IC50) |
AMPK 1512 nM (IC50) |
JNK1 3280 nM (IC50) |
SRC 4330 nM (IC50) |
ZAP70 5050 nM (IC50) |
ERK2 6290 nM (IC50) |
P38α 12050 nM (IC50) |
CYP3A4 16.2 μM (IC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | ≥ 33 mg/mL (78.28 mM) | use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 2 years) or -20°C (up to 1 year); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 5% DMSO + 40% PEG300 + 5% Tween-80 + 50% saline |
|---|---|
| Result | ≥ 2.87 mg/mL (6.81 mM); clear solution |
Protocol 2
| Composition | 5% DMSO + 95% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 2.87 mg/mL (6.81 mM); clear solution |
Protocol 3
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 2.08 mg/mL (4.93 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.08 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (20.8 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 4
| Composition | 10% DMSO + 90% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 2.08 mg/mL (4.93 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.08 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (20.8 mg/mL) to 900 μL 20% SBE-β-CD in saline. 20% SBE-β-CD in saline: dissolve 2 g SBE-β-CD powder in 10 mL saline until clear (4°C, store up to one week). |
Protocol 5
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 2.08 mg/mL (4.93 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.08 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (20.8 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
URMC-099 (URMC099) is tested for its effect on the in vitro growth of "brain homing" MDA-MB-231 BR cells expressing eGFP (eGFP8.4) and of the parental MDA-MB-231 cell line. Cells receive either 200 nM URMC-099 or vehicle alone. Growth rates of URMC-099-treated and vehicle-treated cells are similar. In all cases, cell viability is >99%[2].
In Vivo
URMC-099 has a moderate terminal elimination half-life (t1/2=1.92 h in C57 BL/6 mice at 10 mg/kg oral dosing, 2.14 h in C57 BL/6 mice at 2.5 mg/kg iv, and 2.72 h in C57 BL/6 mice at 10 mg/kg iv)[1]. The in vivo effect of URMC-099 (URMC099) on tumor formation is analyzed in a well characterized mouse xenograft model of breast cancer brain metastasis. In these experiments, immunodeficient nu/nu mice receive eGFP8.4 cells by inoculation into the left ventricle, and the animals are then treated with URMC-099 (10 mg/kg) or vehicle alone every 12 hours for 20 days. This dose is chosen because URMC-099 at this level has been shown to be sufficient for effective MLK3 inhibition in mice, along with good blood-brain barrier penetration and potent inhibition of Jun N-terminal kinase (JNK) phosphorylation in brain tissue. On day 21, the mice are sacrificed and the number of BM is assessed. Each treatment group consists of fifteen mice. BM are detected in 60% of mice, in line with previous studies of this xenograft model by other investigators. The total number of brain metastasis (BM) in mice is significantly increased by URMC-099 treatment (p<0.05, two-tailed t-test). Micrometastases show a pattern similar to that of total BM. Macrometastasis numbers do not differ statistically between URMC-099-treated and vehicle-treated mice[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
Cell Assay[2]
Seed MDA-MB-231, MCF10A, HS578t and MDA-MB-231 EGFP8.4 cells at an initial density of 5.0×104 cells/mL in a 24 well plate, using 0.5 mL of media. Treat the cells with either 200 μM of URMC-099 or vehicle (0.002% DMSO). Determine the cell number in each well by trypsinizing the cells and counting them with a hematocytometer. Test viability by trypan blue dye exclusion. Test each condition in triplicate[2].
Animal Administration[2]
Mice[2] Inject 6 to 8 week old female nu/nu mice intraperitoneally with URMC-099 at 10 mg/kg, or vehicle, twice daily for 20 days. On day 21, sacrifice the mice by CO2 suffocation. Remove the brains, fix them in 4% formaldehyde in PBS overnight, and transfer them to 30% sucrose in PBS. Quickly freeze the brains by immersion in isopentane cooled on dry ice. Section the frozen brains coronally every 30 micrometers. Mount eight sections starting at bregma 2.0 and separated by 360 μm on glass slides for tumor evaluation under the microscope. Count the number of brain metastasis (BM) by examining eGFP signals under a fluorescence microscope at 20× magnification[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload. Cell Death Dis 2020 Jul 24;11(7):574. PMID: 32710001
Xinyang Tablet inhibits MLK3-mediated pyroptosis to attenuate inflammation and cardiac dysfunction in pressure overload. J Ethnopharmacol 2021 Jun 28:274:114078. PMID: 33798659
Opposing USP19 splice variants in TGF-β signaling and TGF-β-induced epithelial-mesenchymal transition of breast cancer cells. Cell Mol Life Sci 2023 Jan 17;80(2):43. PMID: 36646950
Phosphorylation of mixed lineage kinase MLK3 by cyclin-dependent kinases CDK1 and CDK2 controls ovarian cancer cell division. J Biol Chem 2022 Aug;298(8):102263. PMID: 35843311
Murine cytomegalovirus employs the mixed lineage kinases family to regulate the spiral ganglion neuron cell death and hearing loss. Neurosci Lett 2023 Jan 10:793:136990. PMID: 36455693
University of Minnesota. 2025.
Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma. bioRxiv 2023 Sep 12:2023.09.09.557001. PMID: 37745469
