[CAS NO. 1229582-33-5] URMC-099
PRODUCTS SPECIFICATIONS [1229582-33-5]
DESCRIPTION [1229582-33-5]
Overview
| MDL | MFCD28168077 |
|---|---|
| Molecular Weight | 421.54 |
| Molecular Formula | C27H27N5 |
| SMILES | CN(CC1)CCN1CC(C=C2)=CC=C2C3=CN=C4C(C(C5=CC=C(NC=C6)C6=C5)=CN4)=C3 |
5 Publications Citing Use of MCE
Summary
URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 ( MLK3 ) ( IC 50 =14 nM) inhibitor with with excellent blood-brain barrier penetration properties.
IC50 & Target
|
LRRK2 11 nM (IC 50 ) |
FLT3 4 nM (IC 50 ) |
FLT1 39 nM (IC 50 ) |
ABL1 (T315I) 3 nM (IC 50 ) |
ABL1 6.8 nM (IC 50 ) |
SGK 67 nM (IC 50 ) |
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SGK1 201 nM (IC 50 ) |
AurA 108 nM (IC 50 ) |
AurB 123 nM (IC 50 ) |
AurC 290 nM (IC 50 ) |
IKKβ 257 nM (IC 50 ) |
IKKα 591 nM (IC 50 ) |
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TNFα 460 nM (IC 50 ) |
ROCK1 1030 nM (IC 50 ) |
ROCK2 111 nM (IC 50 ) |
CDK1 1125 nM (IC 50 ) |
CDK2 1180 nM (IC 50 ) |
TRKA 85 nM (IC 50 ) |
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c-MET 177 nM (IC 50 ) |
TRKB 217 nM (IC 50 ) |
IGF1R 307 nM (IC 50 ) |
LCK 333 nM (IC 50 ) |
MEKK2 661 nM (IC 50 ) |
SYK 731 nM (IC 50 ) |
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AMPK 1512 nM (IC 50 ) |
JNK1 3280 nM (IC 50 ) |
SRC 4330 nM (IC 50 ) |
ZAP70 5050 nM (IC 50 ) |
ERK2 6290 nM (IC 50 ) |
P38α 12050 nM (IC 50 ) |
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CYP3A4 16.2 μM (IC 50 ) |
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In Vitro
The effect of URMC-099 (URMC099) on the in vitro growth of the “brain homing” MDA-MB-231 BR cells expressing eGFP (eGFP8.4) and their parental cell line, MDA-MB-231 is tested. The cells are treated with either 200 nM URMC-099 or vehicle alone. Cells treated with URMC-099 grow at a similar rate to those treated with vehicle. Cell viability is >99% in all cases [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
URMC-099 has moderate terminal elimination half-life (t 1/2 =1.92 h, 2.14 h and 2.72 h for C57 BL/6 mice (10 mg/kg, oral dosing), C57 BL/6 mice (2.5 mg/kg, iv), C57 BL/6 mice (10 mg/kg, iv)) [1] . The effect of URMC-099 (URMC099) on tumor formation in vivo is analyzed using a well characterized mouse xenograft model of breast cancer brain metastasis. For these experiments, eGFP8.4 cells are inoculated into the left ventricle of immunodeficient nu / nu mice; animals are then treated with either URMC-099 (10 mg/kg) or vehicle alone, every 12 hours for 20 days. This dose of URMC-099 is chosen because it has been shown to be sufficient to effectively inhibit MLK3 in mice, with good penetration of the blood-brain barrier and potent inhibition of the phosphorylation of Jun N-terminal kinase (JNK) in brain tissue. On day 21 the mice are sacrificed and number of BM is assessed. Fifteen mice are used for each treatment group. BM are detected in 60% of mice, which is consistent with previous studies using this xenograft model by other investigators. URMC-099 treatment significantly (p<0.05, two-tailed t-test) increases the total number of brain metastasis (BM) in mice. For micrometastases, the pattern is similar to that observed for total BM. The number of macrometastases is statistically indistinguishable between mice treated with URMC-099 or vehicle [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 33 mg/mL ( 78.28 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3723 mL | 11.8613 mL | 23.7225 mL |
| 5 mM | 0.4745 mL | 2.3723 mL | 4.7445 mL |
| 10 mM | 0.2372 mL | 1.1861 mL | 2.3723 mL |
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1.
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2.
Add each solvent one by one: 5% DMSO >> 95% (20% SBE-β-CD in saline)
Solubility: ≥ 2.87 mg/mL (6.81 mM); Clear solution
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3.
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4.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (4.93 mM); Clear solution
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5.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.93 mM); Clear solution
References
- [1] Goodfellow VS, et al. Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem. 2013 Oct 24;56(20):8032-48.
- [2] Rhoo KH, et al. Pharmacologic inhibition of MLK3 kinase activity blocks the in vitro migratory capacity of breast cancer cells but has no effect on breast cancer brain metastasis in a mouse xenograft model. PLoS One. 2014 Sep 29;9(9):e108487.