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Last update 08 May 2025

Positive transcriptional elongation factor B

Last update 08 May 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with Positive transcriptional elongation factor B

Q205

Target

Positive transcriptional elongation factor B

Mechanism

Positive transcriptional elongation factor B agonists

Active Org.

Southern Medical University

Originator Org.

Southern Medical University

Active Indication

HIV Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

VIP-217

Target

CDK9 x Positive transcriptional elongation factor B

Mechanism

CDK9 inhibitors [+1]

Active Org.

Vincerx Pharma, Inc.

Originator Org.

Bayer AG

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MP-HE-001A

Target

Positive transcriptional elongation factor B x VHL

Mechanism

Positive transcriptional elongation factor B inhibitors [+1]

Active Org.-

Originator Org.

MediaPharma Srl

Active Indication-

Inactive Indication

Vascular Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Positive transcriptional elongation factor B

100 Translational Medicine associated with Positive transcriptional elongation factor B

0 Patents (Medical) associated with Positive transcriptional elongation factor B

Literatures (Medical) associated with Positive transcriptional elongation factor B

15 Mar 2019·Transcription

Therapeutic targeting of transcriptional cyclin-dependent kinases

Review

Author: Espinosa, Joaquín M. ; Galbraith, Matthew D. ; Bender, Heather

The fact that many cancer types display transcriptional addiction driven by dysregulation of oncogenic enhancers and transcription factors has led to increased interest in a group of protein kinases, known as transcriptional cyclin dependent kinases (tCDKs), as potential therapeutic targets. Despite early reservations about targeting a process that is essential to healthy cell types, there is now evidence that targeting tCDKs could provide enough therapeutic window to be effective in the clinic. Here, we discuss recent developments in this field, with an emphasis on highly-selective inhibitors and the challenges to be addressed before these inhibitors could be used for therapeutic purposes. Abbreviations: CAK: CDK-activating kinase;CDK: cyclin-dependent kinase;CMGC group: CDK-, MAPK-, GSK3-, and CLK-like;CTD: C-terminal repeat domain of the RPB1 subunit of RNA polymerase II;DRB: 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole;mCRPC: metastatic castration-resistant prostate cancer;NSCLC: non-small cell lung cancer;P-TEFb: positive elongation factor b;RNAPII: RNA polymerase II;S2: serine-2 of CTD repeats;S5: serine-5 of CTD repeats;S7: serine-7 of CTD repeats;SEC: super elongation complex;tCDK: transcriptional cyclin-dependent kinase;TNBC: triple-negative breast cancer.

05 Nov 2015·OncogeneQ1 · MEDICINE

Disruption of CTCF/cohesin-mediated high-order chromatin structures by DNA methylation downregulates PTGS2 expression

Q1 · MEDICINE

Article

Author: Kim, T Y ; Kang, J Y ; Kim, H P ; Han, S W ; Song, S H ; Yun, J ; Jeon, M S

The CCCTC-binding factor (CTCF)/cohesin complex regulates gene transcription via high-order chromatin organization of the genome. De novo methylation of CpG islands in the promoter region is an epigenetic hallmark of gene silencing in cancer. Although the CTCF/cohesin complex preferentially targets hypomethylated DNA, it remains unclear whether the CTCF/cohesin-mediated high-order chromatin structure is affected by DNA methylation during tumorigenesis. We found that DNA methylation downregulates the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), which is an inducible, rate-limiting enzyme for prostaglandin synthesis, by disrupting CTCF/cohesin-mediated chromatin looping. We show that the CTCF/cohesin complex is enriched near a CpG island associated with PTGS2 and that the PTGS2 locus forms chromatin loops through methylation-sensitive binding of the CTCF/cohesin complex. DNA methylation abolishes the association of the CTCF/cohesin complex with the PTGS2 CpG island. Disruption of chromatin looping by DNA methylation abrogates the enrichment of transcriptional components, such as positive elongation factor b, at the transcriptional start site of the PTGS2 locus. These alterations result in the downregulation of PTGS2. Our results provide evidence that CTCF/cohesin-mediated chromatin looping of the PTGS2 locus is dynamically influenced by the DNA methylation status.

15 Apr 2014·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Heat shock protein 90 controls HIV-1 reactivation from latency

Q1 · CROSS-FIELD

Article

Author: Weinberger, Michael ; Zhyvoloup, Alexander ; Weston, Stuart ; Labokha, Aksana A. ; Fassati, Ariberto ; Low, Jun Siong ; Corazza, Gianmarco ; Marcello, Alessandro ; Anderson, Ian ; Moody, Christopher J. ; Kitson, Russell A.

Latency allows HIV-1 to persist in long-lived cellular reservoirs, preventing virus eradication. We have previously shown that the heat shock protein 90 (Hsp90) is required for HIV-1 gene expression and mediates greater HIV-1 replication in conditions of hyperthermia. Here we report that specific inhibitors of Hsp90 such as 17-(N-allylamino)-17-demethoxygeldanamycin and AUY922 prevent HIV-1 reactivation in CD4+ T cells. A single modification at position 19 in the Hsp90 inhibitors abolished this activity, supporting the specificity of the target. We tested the impact of Hsp90 on known pathways involved in HIV-1 reactivation from latency; they include protein kinase Cs(PKCs), mitogen activated protein kinase/extracellular signal regulated kinase/positive transcriptional elongation factor-b and NF-κB. We found that Hsp90 was required downstream of PKCs and was not required for mitogen activated protein kinase activation. Inhibition of Hsp90 reduced degradation of IkBα and blocked nuclear translocation of transcription factor p65/p50, suppressing the NF-κB pathway. Coimmunoprecipitation experiments showed that Hsp90 interacts with inhibitor of nuclear factor kappa-B kinase (IKK) together with cochaperone Cdc37, which is critical for the activity of several kinases. Targeting of Hsp90 by AUY922 dissociated Cdc37 from the complex. Therefore, Hsp90 controls HIV-1 reactivation from latency by keeping the IKK complex functional and thus connects T-cell activation with HIV-1 replication. AUY922 is in phase II clinical trial and, in combination with a PKC-ϑ inhibitor in phase II clinical trial, almost completely suppressed HIV-1 reactivation at 15 nM with no cytotoxicity. Selective targeting of the Hsp90/Cdc37 interaction may provide a powerful approach to suppress HIV-1 reactivation from latency.

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Positive transcriptional elongation factor B

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