Medicinal Chemistry & Hit to Lead

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