alvocidib) action in part by inhibiting Cdk9 a kinase involved in RNA polymerase II (Pol II)-mediated transcription elongation13. (researchatlanta.org)
also known as flavopiridol) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development by Tolero Pharmaceuticals for the treatment of acute myeloid leukemia. (wikipedia.org)
Clinical1
CYC202 SCH727965) which also target Cdk9 have came into clinical tests13. (researchatlanta.org)
Target1
The target of alvocidib is the positive transcription elongation factor P-TEFb. (wikipedia.org)
Positive transcription elongation2
Eukaryotic protein-coding gene transcription can be governed at multiple amounts, including by the experience from the p-TEFb (positive transcription elongation aspect b) CDK9/cyclinT complicated, which phosphorylates the carboxy-terminal site (CTD) of RNA Polymerase II (RNAPII) on serine residues 2 and 5 of RNA Epigallocatechin gallate Pol II. (bioinf.org)
The target of alvocidib is the positive transcription elongation factor P-TEFb. (wikipedia.org)
Flavopiridol2
Flavopiridol (alvocidib), a pan-CDK inhibitor and powerful inhibitor of p-TEFb [9], was the 1st CDK inhibitor to enter the medical industry. (bioinf.org)
also known as flavopiridol) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development by Tolero Pharmaceuticals for the treatment of acute myeloid leukemia. (wikipedia.org)
Proliferation1
Investigators demonstrated that miR-140-5p was frequently downregulated in breast cancer stem cells (BCSCs), and miR-140-5p mimics could inhibit the proliferation of BCSCs. (stemcellsciencenews.com)
Vitro1
C-type lectin domain family 12 member A (CLL1)-antibody-drug conjugate (CLT030) inhibited in vitro leukemic stem cell colony formation and demonstrated robust in vivo efficacy in acute myeloid leukemia (AML) cell tumor models and tumor growth inhibition in the AML patient-derived xenograft model. (stemcellsciencenews.com)
Transcription1
Pro-longevity protein SIRT1 deacetylated and stabilized the epithelial-to-mesenchymal-transition inducer PRRX1, which inhibited the transcription of core stemness factor KLF4. (stemcellsciencenews.com)
Cells5
Furthermore, CRISPR-Cas CDK9 knock-out activated apoptosis in MM cells and significantly diminished cell development. (bioinf.org)
CDK9 shRNA or CDK9 inhibitors considerably potentiated the susceptibility of MM cells, including bortezomib-resistant cells, to proteasome inhibitors. (bioinf.org)
Analogously, CDK9 or cyclin T1 knock-down or CDK9 inhibitors markedly elevated BH3-mimetic lethality in bortezomib-resistant cells. (bioinf.org)
In preclinical research, alvocidib demonstrated designated activity against MM cells, partly linked to its capability to down-regulate Mcl-1 [9]. (bioinf.org)
Treatment of cells with alvocidib leads to inhibition of P-TEFb and the loss of mRNA production. (wikipedia.org)
Development1
Though it was assumed that this antitumor ramifications of these brokers stemmed from obstructing cell cycle development, it has consequently been shown a sub-set of CDK inhibitors (e.g., the ones that inhibit CDK9) may also take action through a transcriptional system by down-regulating the manifestation of varied short-lived proteins such as for example Mcl-1 and p21CIP1 [10, 11]. (bioinf.org)