HIT (mixture or pure compound)

• A defined position on a compound plate with a measured activity above or below a set threshold values at a single concentration

CONFIRMED HIT (mixture or pure compound)

• A HIT that has been retested under the same assay conditions and for which the bioactivity has shown to be reproducible

QUALIFIED HIT (mixture or pure compound)

• A CONFIRMED HIT in a primary assay1
• Dose response curve in primary screen (IC50/EC50)

QUALIFIED HIT COMPOUND (pure compound)

• Represents a pure chemical compound at a purity level >90%
• Biological properties as a QUALIFIED HIT were re-confirmed
• Chemical structure was independently re-confirmed by analytical means

LEAD (Candidate)

1. Chemistry

• Chemical structure confirmed
• Calculated ADME data not prohibitive
• Path forward to generate independent IP position
• Preliminary structure activity relationship (SAR) - actives and inactives within compound class - available
• Compound amenable to chemical derivatisation
• Scale up of sample provision feasible (100 mg scale)

1. Biology

• Biological rationally defined (target/mechanism)
• Level of innovation/competitive advantage given
• Proof of Principle (PoP) in a relevant model (normally ex vivo or in vivo)

DEREPLICATION means the process of HPLC/MS/UV/ELSD-analytical evaluation of HITS (positives) from Advanced Extracts or Pre-Fracs followed by comparison of obtained analytical data with IMD’s in house proprietary data collection, which comprises chemical, biological and (chemo-) taxonomical data available for said HITs. This processing aims towards the correlation of identified HITs with chemical matter known to IMD. DEREPLICATION results in a commented HIT-list allow PRIORITIZATION of the HITS for or within HIT FOLLOW UP efforts at IMD.

PRIORITISATION is the mutual determination of an order in which HITS will be operatively processed further, based on pre-defined criteria, in order to identify QUALIFIED HITS and QUALIFIED HIT COMPOUNDS. Said criteria will be potency, IMD’s proprietary experience with the utilized biological source materials (Advanced Extracts; Pre-Fracs) or chemical compound classes (Nat-Pure), i.e. knowledge about bioactivities, CLUSTERING, sourcing and other typical properties. PRIORITISATION leads towards high productivity and probability of success.

HIT FOLLOW UP services at IMD usually consist of the following steps:

• Reproduced production of biologically active source material (positives)
• Secondary DEREPLICATION
• BIOASSAY GUIDED ISOLATION
• STRUCTURE ELUCIDATION
• Delivery of (>/= 4 mg) biologically active pure compound for further biological evaluation by customer

BIOASSAY GUIDED ISOLATION is the process of identification of QUALIFIED HIT COMPOUNDS from a natural substance mixture applying chromatographic separation methodology for the fractionation of the mixture followed by biological testing of the obtained fractions in order to identify bioactive compounds. 

STRUCTURE ELUCIDATION is the elucidation of at least the constitution of QUAILIFIED HIT COMPOUNDS out of Advanced Extracts or Pre-Fracs.

CLUSTERING means the grouping of Nat-Pure CONFIRMED HITS based on structural similarity in order to identify representatives out of those groups for further evaluation. Applied as part of the PRIORITISATION, especially in case of high HIT rates. 

HIT QUALIFICATION means the HPLC/MS/UV purity check and identity confirmation of Nat-Pure CONFIRMED HITS, performed by IMD.