Synonym
ML298; ML-298; ML 298; CID53393915;
IUPAC/Chemical Name
3,4-Difluoro-N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-8-yl]ethyl]-benzamide
InChi Key
XAPVAKKLQGLNOY-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H23F3N4O2/c23-16-2-1-3-17(13-16)29-14-27-21(31)22(29)6-9-28(10-7-22)11-8-26-20(30)15-4-5-18(24)19(25)12-15/h1-5,12-13H,6-11,14H2,(H,26,30)(H,27,31)
SMILES Code
O=C(NCCN(CC1)CCC1(N(C2=CC=CC(F)=C2)CN3)C3=O)C4=CC=C(F)C(F)=C4
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ML298 is a potent and selective inhibitor of Phospholipase D2 (PLD2) with an IC50 of 355 nM.
In vitro activity:
Comparable data was generated in the biochemical assay with purified PLD proteins, indicating that 7g acted directly on PLD2. Based on the PLD inhibitory profile, 7g (ML298) was declared an MLPCN probe and assigned as ML298. Thus, at standard in vitro concentrations and in vivo plasma exposures (above 5 μM), ML298 only inhibits PLD2.
Reference: J Med Chem. 2013 Mar 28;56(6):2695-9. https://pubmed.ncbi.nlm.nih.gov/23445448/
In vivo activity:
Thus, in vivo PK in mice (due to future oncology PD models) was dosed IP to diminish first pass effects. This route of administration provided excellent plasma levels for both probes, but while ML299 was CNS penetrant (Brain-AUC/PlasmaAUC of 0.44), ML298 was peripherally restricted (BrainAUC/PlasmaAUC of 0.05). Thus, ML298 compliments 4, which is highly CNS penetrant, providing key tools to dissect selective PLD2 in the periphery as well as in the CNS.
Reference: J Med Chem. 2013 Mar 28;56(6):2695-9. https://pubmed.ncbi.nlm.nih.gov/23445448/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
20.0 |
46.25 |
|
| Ethanol |
1.0 |
2.31 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
432.45
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
O'Reilly MC, Scott SA, Brown KA, Oguin TH 3rd, Thomas PG, Daniels JS, Morrison R, Brown HA, Lindsley CW. Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J Med Chem. 2013 Mar 28;56(6):2695-9. doi: 10.1021/jm301782e. Epub 2013 Mar 13. PMID: 23445448; PMCID: PMC3632306.
In vitro protocol:
O'Reilly MC, Scott SA, Brown KA, Oguin TH 3rd, Thomas PG, Daniels JS, Morrison R, Brown HA, Lindsley CW. Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J Med Chem. 2013 Mar 28;56(6):2695-9. doi: 10.1021/jm301782e. Epub 2013 Mar 13. PMID: 23445448; PMCID: PMC3632306.
In vivo protocol:
O'Reilly MC, Scott SA, Brown KA, Oguin TH 3rd, Thomas PG, Daniels JS, Morrison R, Brown HA, Lindsley CW. Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J Med Chem. 2013 Mar 28;56(6):2695-9. doi: 10.1021/jm301782e. Epub 2013 Mar 13. PMID: 23445448; PMCID: PMC3632306.
1: O'Reilly MC, Scott SA, Daniels JS, Morrison R, Engers JL, Oguin T, Thomas P,
Brown HA, Lindsley CW. A Next generation PLD2 inhibitor with improved
physiochemical properties and DMPK profile for translational in vivo. 2014 Apr 15
[updated 2015 Jan 16]. Probe Reports from the NIH Molecular Libraries Program
[Internet]. Bethesda (MD): National Center for Biotechnology Information (US);
2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK280050/
PubMed PMID: 25834904.
2: Scott SA, O’Reilly MC, Daniels JS, Morrison R, Ptak R, Dawson ES, Tower N,
Engers JL, Engers DW, Oguin T, Thomas P, White L, Brown HA, Lindsley CW.
Development of a Selective, Allosteric PLD2 Inhibitor. 2012 Apr 5 [updated 2013
Mar 14]. Probe Reports from the NIH Molecular Libraries Program [Internet].
Bethesda (MD): National Center for Biotechnology Information (US); 2010-.
Available from http://www.ncbi.nlm.nih.gov/books/NBK143549/
PubMed PMID: 23762931.
3: O'Reilly MC, Scott SA, Brown KA, Oguin TH 3rd, Thomas PG, Daniels JS, Morrison
R, Brown HA, Lindsley CW. Development of dual PLD1/2 and PLD2 selective
inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298
and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J Med
Chem. 2013 Mar 28;56(6):2695-9. doi: 10.1021/jm301782e. Epub 2013 Mar 13. PubMed
PMID: 23445448; PubMed Central PMCID: PMC3632306.
