Table 1 Drugs targeting proteins involved in transcription

H-7

CDK7, CDK8, CDK9

Reduce levels of phosphorylated RNP lII inhibiting elongation

I, II

PKC

Only research

[35–38]

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, 41–43]

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

[33–35, 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, 53–55]

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

[57–63]