ArticleScientific reports2017
Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Hybrid dosing of the cyclin-dependent kinase (CDK) inhibitor flavopiridol in relapsed/refractory mantle cell lymphoma and diffuse large B-cell lymphoma.Leukemia & lymphoma · 2019Trial
- TRMT6-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HEXIM1/P-TEFb complex controls RNA polymerase II pause release and immediate early gene induction following neuronal depolarization.The Journal of biological chemistry · 2026Article
- Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Discovery of a "First-in-Class" Selective Multikinase (CDK4/6/9-AURKA/B) Inhibitor, LCI133, for Neuroblastoma.Journal of medicinal chemistry · 2025Article
- Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.Nature communications · 2025Article
- Total Synthesis of Rohitukine and Dysoline and Their Anticancer Analogues Flavopiridol and IIIM-290.ACS omega · 2025Article
- The oral CDK9 inhibitor voruciclib combined with venetoclax for patients with relapsed/refractory acute myeloid leukemia.Blood neoplasia · 2025Article
- Targeted degradation of CDK9 potently disrupts the MYC-regulated network.Cell chemical biology · 2025Article
- A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.Blood advances · 2025Article
- Redox-neutral α-functionalization of pyrrolidines: facile access to α-aryl-substituted pyrrolidines.RSC advances · 2024Article
- Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers.Journal of medicinal chemistry · 2023Article
- The novel CDK9 inhibitor, XPW1, alone and in combination with BRD4 inhibitor JQ1, for the treatment of clear cell renal cell carcinoma.British journal of cancer · 2023Article
- The Pharmacological Implications of Flavopiridol: An Updated Overview.Molecules (Basel, Switzerland) · 2023Review
- 5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) induces apoptosis in breast cancer cells through inhibiting of Mcl-1 expression.Scientific reports · 2023Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- Addressing Transcriptional Dysregulation in Cancer through CDK9 Inhibition.Biochemistry · 2023Article
- A model to predict the prognosis of diffuse large B-cell lymphoma based on ultrasound images.Scientific reports · 2023Article
- Targeting regulated cell death pathways in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
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13 authors.
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Abstract
Aberrant regulation of BCL-2 family members enables evasion of apoptosis and tumor resistance to chemotherapy. BCL-2 and functionally redundant counterpart, MCL-1, are frequently over-expressed in high-risk diffuse large B-cell lymphoma (DLBCL). While clinical inhibition of BCL-2 has been achieved with the BH3 mimetic venetoclax, anti-tumor efficacy is limited by compensatory induction of MCL-1. Voruciclib, an orally bioavailable clinical stage CDK-selective inhibitor, potently blocks CDK9, the transcriptional regulator of MCL-1. Here, we demonstrate that voruciclib represses MCL-1 protein expression in preclinical models of DLBCL. When combined with venetoclax in vivo, voruciclib leads to model-dependent tumor cell apoptosis and tumor growth inhibition. Strongest responses were observed in two models representing high-risk activated B-cell (ABC) DLBCL, while no response was observed in a third ABC model, and intermediate responses were observed in two models of germinal center B-cell like (GCB) DLBCL. Given the range of responses, we show that CIVO, a multiplexed tumor micro-dosing technology, represents a viable functional precision medicine approach for differentiating responders from non-responders to BCL-2/MCL-1 targeted therapy. These findings suggest that the combination of voruciclib and venetoclax holds promise as a novel, exclusively oral combination therapy for a subset of high-risk DLBCL patients.
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