Inhibiting eukaryotic transcription. Which compound to choose? How to evaluate its activity?

Figures & data

Table 1 Overview of widely used inhibitors of transcription

	Actinomycin D	α–amanitin	DRB	Flavopiridol	Triptolide
Concentration	>0.01 µgml^−1 for class I genes >1 µgml^−1 for class II genes	>2 µgml^−1	100 µM	>0.5 µM	1 µM
Stock solution in	DMSO	aqueous	DMSO	aqueous	DMSO
Target	DNA intercalation	RNAPII >> RNAPIII	CDK9 in P-TEFb	CDK9 in P-TEFb	XPB in TFIIH
	RNA polymerase elongation inhibited	RNA synthesis inhibited	RNAP II elongation inhibited rRNA processing impaired	RNAP II elongation inhibited, rRNA processing impaired	RNAP I and RNAP II initiation inhibited
Target Selectivity	GC-rich DNA sequences	RNAPII & RNAPIII only known targets	Other kinases inhibited	Other kinases inhibited	Other potential target: Polycystin-2 calcium channel
Inhibition Selectivity	Class I >> Class II >> Class III transcription	Class II >> Class III transcription	Class II transcription Class I processing	Class II transcription, Class I processing	Class II & Class I transcription
Consequence on RNA polymerase II	CTD hyperphosphorylation	RNAPII degradation	CTD serine 2 dephosphorylation	CTD serine 2 dephosphorylation	Proteasome-dependent RNAPII degradation
Reversibility	Weak	No	Yes	?	No
Rate	Fast, minutes	Slow, hours	Fast, minutes	Fast, minutes	Fast, minutes