polymerase-ii

RNA polymerase II-IN-1 (compound 19iv), an amatoxin, selectively inhibits RNA polymerase II (Pol II) with an IC50 of 36.66 nM and exhibits heightened cytotoxicity towards cancer cells while reducing toxicity in normal cells compared to α-Amanitin [1].

RNA polymerase II-IN-2 (compound 20iii), a potent inhibitor of RNA polymerase II (Pol II) with a K i value of 9.5 nM, exhibits cytotoxicity against cancer cells, demonstrating toxicity levels 2 and 5 times higher than α-amanitin in CHO and HEK293 cells, respectively [1].

AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC). It interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis. AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II, and acts synergistically with DNA damaging agents to inhibit tumor cell growth.

(S)-Enitociclib (VIP152) is a selective CDK9 inhibitor that induces complete regression of MYC+ lymphomas by inhibiting RNA polymerase II-mediated transcription of anti-apoptotic and pro-survival proteins.

A09-003 is a novel cell cycle protein-dependent kinase-9 CDK-9 inhibitor.A09-003 inhibits the proliferation of a variety of leukemia cell lines and inhibits the increase of leukemia sequence-1 protein in myeloid cells.A09-003 also induces apoptosis, decreases RNA polymerase II activity, and decreases Mcl-1 expression.

AZD-4573 is a selective and short-acting inhibitor of the serine threonine cyclin-dependent kinase 9, the catalytic subunit of the RNA polymerase II elongation factor positive transcription elongation factor b. It also has a potential antineoplastic activ

Mycophenolic acid-d3 (Mycophenolate-d3) is a derivative of Mycophenolic acid. Mycophenolic acid is a compound that reduces GTP level and impacts transcription elongation of RNA polymerase II (RNAP II), promotes proximal site use and reverses the effect of cordyceps on selective polyadenylation.

β-Amanitin, a cyclic peptide toxin found in the poisonous Amanita phalloides mushroom, inhibits eukaryotic RNA polymerase II and III, thereby disrupting protein synthesis.

Mal-C6-α-Amanitin, an ADC (antibody-drug conjugate) linker drug, incorporates the powerful antitumor agent α-Amanitin, an inhibitor of RNA polymerase II, through the Mal-C6 linker, showcasing potent antitumor activity.

5-formylcytosine (5FC) is a rare base found in mammalian DNA. It participates in active DNA demethylation, changes DNA double helix structure, and reduces the transcription rate and substrate specificity of RNA polymerase II.

TAF10 is one of many protein factors or coactivators associated with RNA polymerase II activity. One vial of this peptide may be used as a methyltransferase acceptor peptide for more than 200 reactions at 15 μM.

cDPCP is a platinum-containing DNA-crosslinking agent.1Unlike cisplatin or oxaliplatin , cDPCP forms monofunctional DNA adducts. It is transported into cells by organic cation transporter 1 (OCT1) and OCT2, inhibiting proliferation of MDCK cells expressing the human transporters with IC50values of 8.1 and 1.5 μM, respectively. cDPCP inhibits RNA polymerase II-mediated transcription in a reporter assay using HeLa cells. It increases survival in murine S180 sarcoma and P388 leukemia models when administered at doses of 40 and 80 mg/kg, respectively.2 1.Lovejoy, K.S., Todd, R.C., Zhang, S., et al.cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospectsProc. Natl. Acad. Sci. USA105(26)8902-9807(2008) 2.Hollis, L.S., Amundsen, A.R., and Stern, E.W.Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+J. Med. Chem.32128-136(1989)

γ-Amanitin, an ADC (antibody-drug conjugate) cytotoxin isolated from mushrooms, inhibits RNA polymerase II, disrupting mRNA synthesis. It exhibits effects akin to those of α-Amanitin and β-Amanitin.

ε-Amanitin is a cyclic peptide obtained from various mushroom species. It exhibits a strong affinity for RNA polymerase II and effectively inhibits its activity.

Thio-ITP, also known as 6-Thioinosine 5'-triphosphate, is a competitive inhibitor of RNA polymerase activity. It exhibits a strong apparent affinity towards the polymerases, with Ki values of 40.9 μM for RNA polymerase I and 38.0 μM for RNA polymerase II.

POL1-IN-1 (Compound 3A) can effectively inhibit the transcription of RNA polymerase I in the A375 malignant melanoma cell line but has no effect on polymerase II.

CDK-IN-9 (compound 24) is a potent inhibitor of CDK and acts on CDK2 E (IC50: 4 nM). It functions as a molecular gel that induces interaction between CDK12 and DDB1, and can dephosphorylate retinoblastoma protein and RNA polymerase II, thereby inducing apoptosis.

CDK7-IN-2 is a potent inhibitor of CDK7, which plays a role in transcription initiation via phosphorylation of the Rbpl subunit of RNA polymerase II (RNAPII). CDK7 is linked to the temporal control of the cell cycle and transcriptional activity, and has research potential for aggressive and difficult-to-treat cancers.

BSJ-01-175 is a selective and potent covalent inhibitor of CDK12 13. BSJ-01-175 is significantly selective for cancer cells, exhibits potent inhibition of phosphorylated RNA polymerase II, and significantly downregulates CDK12 target genes.

Pidnarulex HCl is the salt form of CX-5461, a first-in-class non-genotoxic small molecule targeted inhibitor of RNA polymerase I (Pol I) that activates the p53 pathway without causing DNA damage. CX-5461 selectively inhibits rRNA synthesis by Pol I in the nucleolus, but does not inhibit mRNA synthesis by RNA Polymerase II (Pol II) and does not inhibit DNA replication or protein synthesis. Inhibition of Pol I results in nucleolar stress and release of ribosomal proteins (RP) from the nucleolus. The RP bind to Mdm2 and liberate p53 to orchestrate apoptosis in cancer cells. CX-5461 demonstrates a favorable preclinical profile, potently and selectively kills cancer cells, demonstrates robust in vivo efficacy in multiple models, and has demonstrated oral bioavailability in multiple species.

MFH290 is a novel cysteine (Cys)-directed covalent inhibitor of CDK12 13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes. Importantly, these effects were demonstrated to be CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290 and restored Pol II CTD phosphorylation and DNA damage repair gene expression. Consistent with its effect on DNA damage repair gene expression, MFH290 augments the antiproliferative effect of the PARP inhibitor olaparib.

Epolactaene is a neuritogenic compound in human neuroblastoma cells which selectively inhibit the activities of mammalian DNA polymerases and human DNA topoisomerase II.

Ibulocydine is a potent CDK inhibitor. Ibulocydine has high activity against Cdk7 cyclin H Mat1 and Cdk9 cyclin T. Ibulocydine inhibited the growth of HCC cells more effectively than other Cdk inhibitors, including olomoucine and roscovitine, whereas ibulocydine as well as the other Cdk inhibitors and BMK-Y101 minimally influenced the growth of normal hepatocyte cells. Ibulocydine induced apoptosis in HCC cells, most likely by inhibiting Cdk7 and Cdk9. In vitro treatment of HCC cells with ibulocydine rapidly blocked phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II, a process mediated by Cdk7 9. Anti-apoptotic gene products such as Mcl-1, survivin, and X-linked IAP (XIAP) are crucial for the survival of many cell types, including HCC. Following the inhibition of RNA polymerase II phosphorylation, ibulocydine caused rapid down-regulation of Mcl-1, survivin, and XIAP, thus inducing apoptosis. Furthermore, ibulocydine effectively ind......

YKL-5-124 TFA, a potent and selective irreversible covalent inhibitor of CDK7, demonstrates IC50 values of 53.5 nM for CDK7 and 9.7 nM for the CDK7 Mat1 CycH complex. It exhibits over 100-fold selectivity for CDK7 over CDK9 and CDK2, while showing no activity against CDK12 and CDK13. This compound effectively induces cell-cycle arrest, inhibits E2F-driven gene expression, and has minimal impact on the phosphorylation status of RNA polymerase II.