Reactivity axis: Difference between revisions

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Here we describe the reactivity axis in the ZINC15, particularly in the exported subsets available via the [[tranche browser]].
Here we describe the reactivity axis in the ZINC15, particularly in the exported subsets available via the [[tranche browser]].


In the discussion below, ZINC12 standard subsets included: A, B, C, D, E.  
In the discussion below, ZINC12 standard subsets included: A, C, E.  


The ZINC12 subsets known as "clean" subsets were just A, B, C, D.
The ZINC12 subsets known as "clean" subsets were just A and C.
 
The "I" subset was not loaded in ZINC12, and is only available in 2D (and possibly covalent libraries)


== The Reactivity Axis ==
== The Reactivity Axis ==
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! Class !! Nickname !! Description || How computed || Examples || internal score
! Class !! Nickname !! Description || How computed || Examples || internal score
|-
|-
| A ||  Anodyne ||  No flags of any kind set || pattern_origin_fk is null || example || 0
| A ||  Anodyne aka no-PAINS ||  No flags of any kind set || pattern_origin_fk is null || very unlikely to react or cause trouble in any way  || 0
|-
|-
| B || Reserved1 || Future Use || no matches || example || 5
| B || Chromophore || little things people complain about: nitros, chromophores, hydroxamates || not sure || chromophores (assay interference), heptanes (entropy), quarts (not permeable), nitros, hydroxamates. last chance to complain before anodyne  || 5
|-
|-
| C || PAINS sans mechanism || Worst problem is, PAINS without a clear mechanism matches || pattern_origin_fk =2 || example || 10
| C || ZINC clean aka PAINS-ok || Worst problem is a match with a PAINS with not clear mechanism || pattern_origin_fk =2 || many PAINS are simply frequent hitters, and many legitimate bioactives include PAINS.  you may well wish to screen them and use PAINS as an annotation, not a filter || 10
|-
|-
| D || Reserved2 || Future Use || no matches || example || 20
| D || Reserved2 || Future Use || no matches || example || 20
|-
|-
| E || mildly reactive || mildly electrophilic or nucleophilic group, including PAINS where these mechanisms have been assigned. ||  pattern_type_fk in (1,2) || aldhydes, thiols, michael acceptors, epoxides || 30
| E || mildly reactive || mildly electrophilic, nucleophilic group or redox ||  pattern_type_fk in (1,2) || e.g. aldhydes, imines, thiols, michael acceptors, epoxides || 30
|-
|-
| F || Reserved3 || Future Use || no matches || example || 40  
| F || Reserved3 || Future Use || no matches || example || 40  
|-
|-
| G || reactive || electrophile or nucleophile, including PAINS where these mechanisms have been assigned || pattern_type in (3,4) || alpha halo ketones, alkyl halides.  Note includes cancer drugs. || 50
| G || reactive || generally electrophile, nucleophile or redox || pattern_type in (3,4) || e.g.  thiocyanates, isothiocyanates || 50
|-
|-
| H || Reserved4 || Future use || no matches || example || 60
| H || Reserved4 || Future use || no matches || example || 60
|-
|-
| I || Unstable || Highly reactive || pattern_origin=7 || typically reagents, but could be used for covalent binding. e.g. boronic acids || 70
| I || Highly reactive || Too reactive to be considered as non-covalent ligands || pattern_origin=7 || typically reagents; could be used for covalent binding. e.g. boronic acids.  alpha halo ketones, alkyl halides.  Note includes cancer drugs.  || 70
|}
|}


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we need to classify pains by assumed mechanism
we need to classify pains by assumed mechanism
397 pains never hit any compound in zinc




[[Category:ZINC15]]
[[Category:ZINC15]]
[[Category:PAINS]]
[[Category:PAINS]]

Latest revision as of 19:45, 24 March 2018

Here we describe the reactivity axis in the ZINC15, particularly in the exported subsets available via the tranche browser.

In the discussion below, ZINC12 standard subsets included: A, C, E.

The ZINC12 subsets known as "clean" subsets were just A and C.

The "I" subset was not loaded in ZINC12, and is only available in 2D (and possibly covalent libraries)

The Reactivity Axis

Class Nickname Description How computed Examples internal score
A Anodyne aka no-PAINS No flags of any kind set pattern_origin_fk is null very unlikely to react or cause trouble in any way 0
B Chromophore little things people complain about: nitros, chromophores, hydroxamates not sure chromophores (assay interference), heptanes (entropy), quarts (not permeable), nitros, hydroxamates. last chance to complain before anodyne 5
C ZINC clean aka PAINS-ok Worst problem is a match with a PAINS with not clear mechanism pattern_origin_fk =2 many PAINS are simply frequent hitters, and many legitimate bioactives include PAINS. you may well wish to screen them and use PAINS as an annotation, not a filter 10
D Reserved2 Future Use no matches example 20
E mildly reactive mildly electrophilic, nucleophilic group or redox pattern_type_fk in (1,2) e.g. aldhydes, imines, thiols, michael acceptors, epoxides 30
F Reserved3 Future Use no matches example 40
G reactive generally electrophile, nucleophile or redox pattern_type in (3,4) e.g. thiocyanates, isothiocyanates 50
H Reserved4 Future use no matches example 60
I Highly reactive Too reactive to be considered as non-covalent ligands pattern_origin=7 typically reagents; could be used for covalent binding. e.g. boronic acids. alpha halo ketones, alkyl halides. Note includes cancer drugs. 70

other concepts mentioned, must be fit in: chelation, redox, covalent, amphiphilicity

poor derivatizability, optimizability

we never build protomers of H, G, F.

we need to classify pains by assumed mechanism

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