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Table 1 Drugs targeting proteins involved in transcription

From: The basal transcription machinery as a target for cancer therapy

Drug Target Mechanism of action Class gene inhibited Other targets Cancer treatment References
H-7 CDK7, CDK8, CDK9 Reduce levels of phosphorylated RNP lII inhibiting elongation I, II PKC Only research [3538]
H-8 CDK7, CDK9, CDK8 Reduce levels of phosphorylated RNP II inhibiting elongation I, II PKA, PKC, PKG, MLCK Only research [29, 30]
AT8319 CDK9 Inhibits RNP II phosphorylation on Ser 2 disrupting transcription elongation II ND MM, advanced solid tumors, and refractory non-Hodgkin’s lymphoma [34]
Dinaciclib/ SCH-727965 CDK9 Inhibits RNP II phosphorylation on Ser 2 disrupting transcription elongation. Impaired rRNA processing I, II CDK1, CDK2, CDK4, CDK5, CDK7 Solid tumors, hematologicalmalignancies, MM, melanoma, plasma cell neoplasia [33, 34]
RGB-286638 CDK9 Inhibits Ser 2 phosphorylation of RNP II disrupting transcription elongation II CDK1, CDK2, CDK4, CDK5, CDK6, CDK7 Hematological malignancies [34]
R547 CDK9 Inhibits Ser 2 phosphorylation of RNP II disrupting transcription elongation II CDK1, CDK2, CDK4, CDK5, CDK7 Solid tumors [34, 39]
P276-00 CDK9 Inhibits transcription elongation II CDK1, CDK4 MM, breast, pancreas, melanoma, MCL, HNSCC [34]
DRB CDK9 Inhibits RNP II phosphorylation on Ser 2. Impaired rRNA processing I, II CDK2, CDK4, CDK7, CDK8, casein kinase I and II Only Research [33, 34, 40]
Roscovitine/ Seliciclib CDK7 and CDK9 Acts as a competitor for ATP binding inhibiting kinase activity and Ser 5 phosphorylation or RNP II Inhibits rRNA processing I, II Cdc2, CDK2, CDK5, Erk1, Erk2, Dyrk, piridoxal kinase Breast, solid tumors, B-cell malignancies, non-small cell lung cancer, and nasopharyngeal cancer [33, 4143]
ARC CDK9 Inhibits phosphorylation Ser 2 and Ser 5 of RNP II inhibiting transcription elongation II PKC CLL, ALL, hairy cell leukaemia [5, 44]
ZK 304709 CDK7, CDK9 Inhibits RNP II phosphorylation on Ser 2. II CDK1, CDK2, CDK4, VEGFR1-3, PDGFR-β, Flt-3 Relapsed and/or refractory tumors [45]
Wogonin CDK9 Inhibits RNP II phosphorylation on Ser 2. II CDK7 Xenografts [46]
CDKI-71 CDK9 Inhibits RNP II phosphorylation on Ser 2. II CDK1, CDK2, CDK7, CDK6 Under evaluation in cancer cell lines [47]
Flavopiridol CDK9, CDK8 Inhibits phosphorylation of Ser 2 in CTD of RNPII and interrupts RNA elongation; impaired rRNA processing I, II CDK1, CDK2, CDK4, CDK6, CDK7, PKC, Src, EGFR, ERK1 CLL, MM, MCL, indolent B-cell non-Hodgkin’s lymphomas, germ line tumor, melanoma, ALM [3335, 48]
SNS-032 CDK9 Inhibits Ser 2 phosphorylation of RNP II disrupting transcription elongation II CDK2, CDK7, GSK3 CLL, ALL, MM [34, 45]
AT7519 CDK9 Inhibit RNP II phosphorylation of Ser 2 and 5 II CDK2, CDK4, CDK5, GSK-3 MM, solid tumor [34, 45, 49]
CX-5461 SL1 complex Disrupts formation of SL1-rDNA complex I ND Lymphoma and leukemia human cancer xenograft model [3, 671]
α-amatinin RNP II and III Binds to the largest subunit of RNP II and RNP III II, III ND None due to hepatotoxicity [33, 50]
TAS-106 RNA polymerases Ribonucleoside Inhibits RNA polymerases I, II and III ND Solid tumors [51, 52]
Triptolide XPB subunit of TFIIH Inhibits RNP I and II by inhibiting XPB ATPase activity. It triggers RNP II degradation I, II Polycystin-2 calcium channel, ADAM10. Leukemia, myeloma, lymphoma, cholangiosarcoma, hepatocelular, cervical, pancreatic, gastric and oral cancer, anaplastic thyroid carcinoma [33, 39, 5355]
BMH-21 RNA polymerase I Degradation of the RPA194 subunit of the RNA polymerase I I Induce p53 Melanoma [56]
  XPB subunit of TFIIH Promotes XPB degradation II Antagonist of aldosterone Sensitizes carcinoma cells to cis- platinium [57]
JQ1 and I-BET151 BRD3 and BRD4 Displace BRD3 and BRD4 from chromatin II ND Multiple myeloma, leukaemia, lymphoma and lung adenocarcinoma in animal models [5763]
  1. Abbreviations: ND, non detected; CLL, chronic lymphocytic leukemia; ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia, CML, chronic myelogenousleukemia; HNSCC, head and neck squamous cell carcinoma; MCL, mantle cell lymphoma; MM, multiple myeloma.