Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C25H15ClF2N4O2 |
| Molecular Weight | 476.862 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)C1=CC=C(NC2=NC3=C(CN=C(C4=CC(Cl)=CC=C34)C5=C(F)C=CC=C5F)C=N2)C=C1
InChI
InChIKey=HHFBDROWDBDFBR-UHFFFAOYSA-N
InChI=1S/C25H15ClF2N4O2/c26-15-6-9-17-18(10-15)23(21-19(27)2-1-3-20(21)28)29-11-14-12-30-25(32-22(14)17)31-16-7-4-13(5-8-16)24(33)34/h1-10,12H,11H2,(H,33,34)(H,30,31,32)
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20607239
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20607239
MLN8054 is a reversible, ATP competitive inhibitor of recombinant Aurora A, developed by Millennium Pharmaceuticals. MLN8054 was tested in phase I clinical trials against advanced solid tumors. Reversible somnolence probably due to off-target inhibition of alpha-1 subunit of GABA-A receptor was dose limiting and prevented achievement of plasma concentrations predicted necessary for target modulation.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL4722 |
4.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2129 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239 |
20 mg 4 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MLN8054 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2642 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239 |
15 mg 4 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MLN8054 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10109 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239 |
20 mg 4 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MLN8054 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
13203 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239 |
15 mg 4 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MLN8054 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. | 2007 Mar 6 |
|
| A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B. | 2009 May 28 |
|
| Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
| Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase. | 2011 Jan 13 |
|
| Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
Patents
Sample Use Guides
In clinical trials against advanced solid tumors MLN8054 was administered orally in multiple divided daily doses for 7 days to 21 consecutive days. A 14-day recovery period followed each dosing period, regardless of its duration. MLN8054 was supplied in capsules of 5 mg or 25 mg. MLN8054 will be given on an empty stomach. Patients were instructed to take nothing by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose.
Route of Administration:
Oral
Recombinant murine Aurora A protein was expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A was conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) was assayed in 50 mM Hepes (pH 7.5)/10 mM MgCl2/5 mM DTT/0.05% Tween 20/2 μM peptide substrate/3.3 μCi/ml [γ-33P]ATP at 2 μM by using Image FlashPlates (Perkin–Elmer).
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DB13061
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C518940
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869363-13-3
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11712649
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100000175308
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BX854EHD63
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C61075
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DTXSID10235987
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CHEMBL259084
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
