Reactivity axis: Difference between revisions

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


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


ZINC "clean" subsets were just A, B, C, D.
The ZINC12 subsets known as "clean" subsets were just A and C.  


== The Clean Axis ==
The "I" subset was not loaded in ZINC12, and is only available in 2D (and possibly covalent libraries)
 
== The Reactivity Axis ==
{| class="wikitable"
{| class="wikitable"
|-
|-
! Class !! Nickname !! Description || How computed
! Class !! Nickname !! Description || How computed || Examples || internal score
|-
|-
| A ||  Anodyne ||  No flags of any kind set || no pattern matches whatsoever
| 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 || Unnecessarily complex || The worst feature is the molecules are over decorated e.g. too many chlorides  || complex, requires representative in A. This is really reserved for future use, and gives us the opportunity to split "super clean" into A (representatives) and B (versions of A)  
| 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 || Chromophore || Worst problem is a chromophore that could interfere with some asays || extended conjugated system, pattern_type = 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 || Any PAINS || Any pains pattern not covered in E,F,G,H || pattern_type= 8 (call it mild PAINS, or pains we don't necessarly believe in because there is no clear MOA)
| D || Reserved2 || Future Use || no matches || example || 20
|-
|-
| E || mildly electrophilic or nucleophilic || aldhydes, thiols, michael acceptors, epoxides || pattern_type in (1,2)
| 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 || strongly electrophilic or nucleophilic || alpha halo ketones, alkyl halides.  Note includes cancer drugs. || pattern_type in (3,4)
| F || Reserved3 || Future Use || no matches || example || 40
|-
|-
| G || unstable in buffer || typically reagents, but could be used for covalent binding. e.g. boronic acids || pattern_type = 10
| G || reactive || generally electrophile, nucleophile or redox || pattern_type in (3,4) || e.g. thiocyanates, isothiocyanates || 50
|-
|-
| H || nonsensical || idea from the PAINS papers || pattern_type = 14.  This is a container, but generally we are not expecting to find any of these in ZINC.
| 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
|}
|}


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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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