polymerase-II

FIT-039 is a selective and ATP-competitive, orally active inhibitor of CDK9( IC50 : 5.8 μM;CDK9/cyclin T1). FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses.

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].

Ibezapolstat (ACX-362E) is an orally active DNA polymerase IIIC inhibitor, an antibiotic with antibacterial activity that inhibits Clostridioides difficile (C. difficile) and can be used for studying Clostridioides difficile infections.

ML-60218 is an inhibitor of broad-spectrum RNA pol III with IC50s of 32 and 27 μM for Saccharomyces cerevisiae and human. ML-60218 disrupts already assembled viroplasms and hampers the formation of new viroplasms.

AOH1996 belongs to small molecule inhibitors and is a PCNA ligand targeting transcription-replication conflicts, with oral activity, metabolic stability, and tumor selectivity. This compound induces transcription-dependent DNA double-strand breaks and apoptosis, and is used for antitumor therapy.

(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.

CBL 0100 free base is an HIV-1 transcription inhibitor that blocks HIV-1 replication and reactivation in vitro and in ex vivo models. It targets the chromatin-associated transcription (FACT) complex, reducing the occupancy of RNA Polymerase II and FACT in the HIV-1 promoter region, and can be used as a latency-reversing agent (LRA) in cART therapy.

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 is a derivative of Mycophenolic acid. Mycophenolic acid (T1335) 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.

(+)-Enitociclib ((+)-BAY-1251152) is the isomer of Enitociclib, a selective CDK9 inhibitor and apoptosis inducer that suppresses CDK9 activity, reduces Ser2 phosphorylation of the RNA polymerase II C-terminal domain.

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.

CDK12/13-IN-3 (Compound 12b) is an orally active CDK inhibitor targeting CDK12 and CDK13, with IC50 values of 107.4 nM and 79.4 nM, respectively. This compound inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression involved in the DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative effects against various cancer cells with nanomolar IC50 values. In mouse models, it demonstrates antitumor activity, favorable pharmacokinetic properties, and an oral bioavailability of 53.6%.

CDK12-IN-8 (Compound Cpd143) is an orally active, highly selective inhibitor of cyclin-dependent kinase 12 (CDK12). It blocks the phosphorylation of serine 2 in the C-terminal domain (CTD) of RNA polymerase II, thereby interfering with gene transcription elongation and DNA damage repair pathways. CDK12-IN-8 holds potential for research in cancers with high CDK12 expression, such as small cell lung cancer and triple-negative breast cancer.

YX0597 is a potent and selective CDK9 PROTAC degrader that reduces RNA polymerase II S2 phosphorylation and MCL1 expression in GA0518 and AGS cells. It effectively inhibits the growth of GEAC cells (including radioresistant tumors) and suppresses tumor proliferation, metastasis, and cancer stem cells.

LPPM-8 is a ligand for Med25 and acts as an inhibitor of Med25 protein-protein interactions (PPI). It engages with Med25 via the H2 surface of its activator-interaction domain, thereby stabilizing full-length proteins in the cellular proteome. LPPM-8 is an orthosteric inhibitor of H2-binding transcription activators (e.g., ATF6a). Med25 plays a role in the transcriptional regulation of RNA polymerase II-dependent genes and can form a transcription complex with ATF6α. LPPM-8 is valuable for studying the complex biology of Med25 and its Mediator complex.

CDK9-IN-39 (1-7a-B1) is an orally active inhibitor of cyclin-dependent kinase 9 (CDK9), with an IC50 value of 6.51 nM. By inhibiting the phosphorylation of RNA polymerase II at the Ser2 site, CDK9-IN-39 induces cell (apoptosis) and can be used for colorectal cancer research.

KI-DX-014 is a DDX21 inhibitor with an IC50 of 3.31 μM. It effectively disrupts the interaction between DDX21 and RNA, modulates ATPase activity, and influences the formation of biomolecular condensates. This compound reduces the release of DDX21-dependent P-TEFb from the 7SK snRNP complex, inhibits RNA polymerase II CTD phosphorylation, and induces developmental defects in zebrafish embryos. KI-DX-014 is applicable in research related to cancer and neurodegenerative diseases.

ZLMT-72 is an orally active dual inhibitor of CDK2 and CDK9, with IC50 values of 0.741 nM and 1.03 nM, respectively. It shows excellent selectivity in kinase profiling and cholinesterase inhibition activity assays. ZLMT-72 exhibits significant antiproliferative effects on colorectal cancer (CRC) cell line HCT116 (GI50 < 0.1 nM). This compound induces apoptosis by inhibiting the phosphorylation of retinoblastoma protein and RNA polymerase II, leading to the downregulation of anti-apoptotic proteins (Mcl-1 and XIAP). ZLMT-72 is suitable for colorectal cancer (CRC) research.

SY-5102 is a potent, selective, orally active cyclin-dependent kinase (CDK7) inhibitor with a Kd of 0.03 nM. It exhibits antiproliferative activity against HCC70 cells with an EC50 of 9 nM. SY-5102 inhibits CDK7-mediated CAK function [downregulating CDK2Thr160 phosphorylation] and TFIIH transcription function [downregulating RNA polymerase II Ser5 phosphorylation]. The compound induces G2/M cell cycle arrest, downregulates the expression of the oncogene c-Myc, and ultimately triggers apoptosis in cancer cells. SY-5102 is applicable for research in triple-negative breast cancer (TNBC).

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.