Figure 1.

Drugs targeting the TFIIH transcription/DNA repair complex. TFIIH is a 10-subunit complex composed of a core (In red; XPB, p62, p52, p44, p34 and TTDA) associated to the CAK (In blue; Cdk7, CycH and MAT1) through MAT1 and the XPD subunit (In green). Four enzymatic activities are found in TFIIH; XPB and XPD are 3′ to 5′ and 5′ to 3′ helicases, Cdk7 is a kinase, and p44 has been described as an E3 ubiquitin ligase in yeast. Triptolide (TPL) is a diterpenoid epoxide that is endogenously produced by the thunder god vine, Tripterygium wilfordii and which targets the ATPase activity of XPB. Minnelide is water soluble pro-drug of TPL synthesized at the University of Minnesota (Minnesota and triptolide) by adding a phosphate ester group. Spironolactone is a potassium-sparing diuretic that induced the specific degradation of XPB through the proteasome pathway. THZ1 is phenylaminopyrimidinyl-acrylamide compound that acts as a highly potent, selective, ATP-site directed, and irreversible inhibitor of CDK7