Medicinal Chemistry & Hit to Lead
Sirius offer fast, high quality Plate-Based assays for Medicinal Chemistry and Hit to Lead stages of drug development. We also offer consultancy where we will work with your chemists to provide context for the physicochemical data and training in the understanding of the parameters.
This service is ideally suited for start-ups who don't have in-house PhysChem capabilities and for analytical support departments in major Pharma that need to fully understand the value of the data they are acquiring.
Objectives:
- Assays designed for 10mM DMSO stocks
- Analysis of large batches of compounds
- Fast turnaround
- Straightforward, standardised assay conditions
Assays Available:
Detailed Assay Information:
Plate Based pKa
Available under aqueous or cosolvent conditions.
pKas are screened using a fast pH/UV hybrid method. Any UV active pKas between 2 and 12 are detected.
Turbidity detection can identify compounds which precipitate.
Requires:
- 150ul of 10mM DMSO stock, or enough solid to create the stock ourselves.
- Client to select required condition (aqueous or cosolvent) in advance.
Delivers:
- Table of pKa results (failures due to precipitation or no UV absorption are indicated)
- Method overview
- Distribution of Species plots for all successful samples
- Molar absorption plots for UV active species of successful samples
Plate Based logD
LogD screening at a fixed pH's of 2.5, 4.5 and 7.4, with a HPLC approach using octanol coated columns.
Requires:
- 150ul of 10mM DMSO stock, or enough solid to create the stock ourselves.
Delivers:
- Table of logD results at specified pH values
- Chromatograms
- Method overview
Plate Based Solubility
Plate based solubility assay. Kinetic or thermodynamic. Assay can be performed at pH2.0 (stomach), pH4.5 (intestinal) and pH7.4 (blood). Compounds added to buffer, left for a set time period, then filtered and the concentration assayed by UV.
Requires:
- 150ul of 10mM DMSO stock, or enough solid to create the stock ourselves.
Delivers:
- Table of solubility results (where no precipitate is observed, it will be stated that the solubility is greater than the experimental concentration).
- UV spectra
- pH vs solubility profile (if more than one pH point is measured).
Plate Based Stability
Compounds are screened for stability at low pH (2.0) and high pH (12.0).
Requires
- 150ul of 10mM DMSO stock, or enough solid to create the stock ourselves.
- Client to select required conditions in advance (i.e. low pH, high pH, and timeframe)
Delivers
- Table of observations (i.e. compound is unstable or not under the specified conditions)
- UV spectra of any species detected
Plate Based PAMPA
Measures rate of passage of a compound through a lipid/alkane membrane. Uses 96 well plates of compound stocks. pH can be adjusted between pH 3 and pH 10. Compound concentration in both Acceptor and Donor layers assayed using UV absorbance.
Requires:
- 150ul of 10mM DMSO stock, or enough solid to create the stock ourselves.
- Client to choose pH conditions and membrane type
Delivers:
- Table of Permeability results
- Membrane retention
- pH vs Permeability plot (if more than one pH studied)
Plate Based PhysChem Bundle
pKa, logD, Solubility, stability and PAMPA analysis at a reduced bundle rate.
Requires:
- 500ul of 10mM DMSO stock, or enough solid to create the stock ourselves.
Delivers:
- Screening pKa results
- Screening LogD results
- Screening Solubility results
- Screening Stability results
- Screening PAMPA results
To use the service, simply fill in a sample submital form:
Click here for plate based assay submital formSirius appointed as distributors for Kibron Delta-8
24.7.08
Sirius are now the exclusive distributors in UK, USA and Canada for the Kibron Delta-8 system for measurement of surface tension and phospholipidosis.
Cambridge scientists set solubility challenge
11.8.08
A new paper from scientists using Sirius solubility techniques at the University of Cambridge asks "can you predict solubilities of 32 molecules using a database of 100 reliable measurements?".
AAPS Annual Meeting
16.11.08
Sirius will have a booth (#1460) at this years AAPS Annual Meeting in Atlanta, Georgia.