1. MAPK/ERK Pathway
    Autophagy
  2. Mixed Lineage Kinase
    Autophagy
  3. URMC-099

URMC-099 

Cat. No.: HY-12599 Purity: 99.90%
Handling Instructions

URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 (MLK3) (IC50=14 nM) inhibitor with with excellent blood-brain barrier penetration properties.

For research use only. We do not sell to patients.

URMC-099 Chemical Structure

URMC-099 Chemical Structure

CAS No. : 1229582-33-5

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 66 In-stock
Estimated Time of Arrival: December 31
5 mg USD 60 In-stock
Estimated Time of Arrival: December 31
10 mg USD 90 In-stock
Estimated Time of Arrival: December 31
50 mg USD 270 In-stock
Estimated Time of Arrival: December 31
100 mg USD 450 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 1 publication(s) in Google Scholar

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Description

URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 (MLK3) (IC50=14 nM) inhibitor with with excellent blood-brain barrier penetration properties.

IC50 & Target

MLK3

14 nM (IC50)

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)

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].

In Vivo

URMC-099 has moderate terminal elimination half-life (t1/2=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].

Molecular Weight

421.54

Formula

C₂₇H₂₇N₅

CAS No.

1229582-33-5

SMILES

CN(CC1)CCN1CC(C=C2)=CC=C2C3=CN=C4C(C(C5=CC=C(NC=C6)C6=C5)=CN4)=C3

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
In Vitro: 

DMSO : ≥ 33 mg/mL (78.28 mM)

H2O : < 0.1 mg/mL (insoluble)

*"≥" means soluble, but saturation unknown.

Preparing
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
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.17 mg/mL (5.15 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.17 mg/mL (5.15 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.17 mg/mL (5.15 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Cell Assay
[2]

MDA-MB-231, MCF10A, HS578t and MDA-MB-231 EGFP8.4 cells are seeded in a 24 well plate at an initial density of 5.0×104 cells/mL in 0.5 mL of media. The cells are treated with either 200 µM of URMC-099 or vehicle (0.002% DMSO). Cell number in each well is measured by trypsinizing the cells and counting them with a hematocytometer. The viability is tested by trypan blue dye exclusion. Each condition is tested in triplicate[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Mice[2]
6 to 8 week old female nu/nu mice are injected intraperitoneally with URMC-099 at a dose of 10 mg/kg, or vehicle, twice daily for 20 days. On day 21 mice are sacrificed by CO2 suffocation. Brains are removed and fixed with 4% formaldehyde in PBS overnight, then transferred to 30% sucrose in PBS. The brains are then quickly frozen by immersing into isopentane cooled on dry ice. The frozen brains are sectioned coronally every 30 micrometers. Eight sections starting at bregma 2.0 and separated by 360 µm are mounted on glass slides for tumor evaluation under the microscope. The number of brain metastasis (BM) is counted by examining eGFP signals under a fluorescence microscope at 20× magnification[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Purity: 99.90%

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Keywords:

URMC-099URMC099URMC 099Mixed Lineage KinaseAutophagyMLKsInhibitorinhibitorinhibit

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URMC-099
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