Number three substituted (5)
I believe the answer is:
ether
'number' is the definition.
(I've seen this before)
'three substituted' is the wordplay.
'substituted' is an anagram indicator (I've seen 'substitute' mean this).
'three' is an anagram of 'ETHER'.
(Other definitions for ether that I've seen before include "Light liquid used as anaesthetic" , "It could knock you out" , "Anaesthetic; clear sky (poetic)" , "Former anaesthetic" , "Chemical solvent" .)