Reactivity axis

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