NELF Inhibitors
NELF inhibitors constitute a diverse class of compounds that modulate the activity of NELF, a key regulator of RNA polymerase II (Pol II) pausing. These inhibitors can be categorized into direct and indirect inhibitors based on their mechanisms of action. Direct inhibitors, such as Triptolide, Flavopiridol, DRB, and THZ1, act by targeting components of the positive transcription elongation factor b (P-TEFb) complex, specifically CDK9. Triptolide, for instance, disrupts RNA polymerase II pausing by binding to the catalytic subunit of P-TEFb, releasing Pol II from promoter-proximal pausing and promoting transcriptional elongation. Similarly, Flavopiridol inhibits NELF by blocking CDK9 activity, preventing phosphorylation of Pol II and enhancing transcriptional elongation.
Indirect inhibitors, such as Actinomycin D, Alpha-Amanitin, JQ1, and C646, exert their effects by influencing various cellular processes related to transcription. Actinomycin D and Alpha-Amanitin disrupt transcription initiation by binding to DNA or RNA polymerase II, respectively, leading to reduced Pol II recruitment and preventing NELF-mediated pausing. JQ1, on the other hand, indirectly inhibits NELF by targeting BRD4, disrupting the formation of the Super Elongation Complex (SEC) and preventing SEC recruitment to chromatin. Lastly, C646 indirectly inhibits NELF by targeting the histone acetyltransferase (HAT) activity of p300/CBP, altering chromatin accessibility and reducing the formation of pausing complexes on target genes. Furthermore, compounds like Camptothecin and I-BET151 demonstrate indirect inhibition through DNA damage response pathways or disruption of SEC formation, respectively, influencing NELF-mediated pausing. In summary, the chemical class of NELF inhibitors encompasses a range of compounds with distinct mechanisms of action, directly or indirectly modulating the pausing and elongation dynamics of RNA polymerase II. Understanding the intricate regulatory network involving NELF and its inhibitors provides valuable insights into potential strategies for conditions where transcriptional dysregulation is implicated.
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Triptolide | 38748-32-2 | sc-200122 sc-200122A | 1 mg 5 mg | $90.00 $204.00 | 13 | |
Triptolide inhibits NELF directly by disrupting RNA polymerase II (Pol II) pausing. It binds to the catalytic subunit of the P-TEFb complex, releasing Pol II from promoter-proximal pausing. This direct inhibition allows for enhanced transcriptional elongation and prevents NELF-mediated pausing of Pol II. | ||||||
Flavopiridol | 146426-40-6 | sc-202157 sc-202157A | 5 mg 25 mg | $78.00 $259.00 | 41 | |
Flavopiridol inhibits NELF directly by targeting CDK9 within the P-TEFb complex. By blocking CDK9 activity, Flavopiridol prevents the phosphorylation of Pol II and inhibits NELF-mediated pausing. This direct inhibition promotes efficient transcriptional elongation by facilitating the release of Pol II from paused complexes. | ||||||
DRB | 53-85-0 | sc-200581 sc-200581A sc-200581B sc-200581C | 10 mg 50 mg 100 mg 250 mg | $43.00 $189.00 $316.00 $663.00 | 6 | |
DRB inhibits NELF directly by interfering with the function of CDK9 in the P-TEFb complex. Through the inhibition of CDK9, DRB disrupts the phosphorylation of Pol II and impedes NELF-mediated pausing. This direct inhibition promotes the transition from paused to elongating Pol II, facilitating transcriptional activity. | ||||||
THZ1 | 1604810-83-4 | sc-507542 | 1 mg | $95.00 | ||
THZ1 inhibits NELF directly by targeting CDK7, a component of the P-TEFb complex. By inhibiting CDK7, THZ1 disrupts the phosphorylation of Pol II and prevents NELF-mediated pausing. This direct inhibition facilitates the release of Pol II from promoter-proximal regions, promoting transcriptional elongation and preventing pausing. | ||||||
Actinomycin D | 50-76-0 | sc-200906 sc-200906A sc-200906B sc-200906C sc-200906D | 5 mg 25 mg 100 mg 1 g 10 g | $74.00 $243.00 $731.00 $2572.00 $21848.00 | 53 | |
Actinomycin D inhibits NELF indirectly by intercalating into DNA and preventing transcription initiation. By binding to the DNA template, Actinomycin D hinders the assembly of the transcriptional machinery, leading to reduced Pol II recruitment. This indirect inhibition results in the prevention of NELF-mediated pausing by limiting transcription initiation. | ||||||
α-Amanitin | 23109-05-9 | sc-202440 sc-202440A | 1 mg 5 mg | $269.00 $1050.00 | 26 | |
Alpha-Amanitin inhibits NELF indirectly by selectively inhibiting RNA polymerase II (Pol II) during transcription elongation. By binding to the Pol II enzyme, Alpha-Amanitin halts the elongation process, preventing NELF-mediated pausing. This indirect inhibition disrupts the normal transcriptional cycle, leading to decreased pausing and enhanced elongation. | ||||||
(±)-JQ1 | 1268524-69-1 | sc-472932 sc-472932A | 5 mg 25 mg | $231.00 $863.00 | 1 | |
JQ1 inhibits NELF indirectly by targeting BRD4 and disrupting the formation of the Super Elongation Complex (SEC). By inhibiting BRD4, JQ1 prevents SEC recruitment to chromatin, inhibiting NELF-mediated pausing. This indirect inhibition promotes transcriptional elongation by preventing the formation of pausing complexes on target genes. | ||||||
Camptothecin | 7689-03-4 | sc-200871 sc-200871A sc-200871B | 50 mg 250 mg 100 mg | $58.00 $186.00 $94.00 | 21 | |
Camptothecin inhibits NELF indirectly by inducing DNA damage and activating DNA damage response pathways. The activation of these pathways leads to the inhibition of transcription initiation, preventing NELF-mediated pausing. This indirect inhibition disrupts the normal transcriptional cycle, reducing the formation of pausing complexes on target genes. | ||||||
C646 | 328968-36-1 | sc-364452 sc-364452A | 10 mg 50 mg | $265.00 $944.00 | 5 | |
C646 inhibits NELF indirectly by targeting the histone acetyltransferase (HAT) activity of p300/CBP. By inhibiting p300/CBP, C646 alters chromatin accessibility, preventing NELF-mediated pausing. This indirect inhibition promotes transcriptional elongation by influencing the epigenetic landscape and reducing the formation of pausing complexes on target genes. | ||||||
I-BET 151 Hydrochloride | 1300031-49-5 (non HCl Salt) | sc-391115 | 10 mg | $450.00 | 2 | |
I-BET151 inhibits NELF indirectly by targeting BRD4 and disrupting the formation of the Super Elongation Complex (SEC). By inhibiting BRD4, I-BET151 prevents SEC recruitment to chromatin, inhibiting NELF-mediated pausing. This indirect inhibition promotes transcriptional elongation by preventing the formation of pausing complexes on target genes. | ||||||