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DRUG CLASS:

RNA polymerase inhibitor

14h
In-silico identification and validation of Silibinin as a dual inhibitor for ENO1 and GLUT4 to curtail EMT signaling and TNBC progression. (PubMed, Comput Biol Chem)
Nevertheless, repression of EMT and Wnt pathway progression by Silibinin was perceived from the gene expression studies. Overall, the current study highlights the tweaking of intricate signaling crosstalk between glycolysis and the Wnt pathway in TNBC cells through inhibiting ENO1 and GLUT4.
Journal
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ENO1 (Enolase 1) • SLC2A4 (Solute Carrier Family 2 Member 4)
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Legalon (silibinin)
7d
Lurbinectedin or in Combination with Irinotecan Versus Topotecan in Patients with Relapsed SCLC (clinicaltrials.gov)
P3, N=180, Recruiting, Luye Pharma Group Ltd. | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
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irinotecan • topotecan • Zepzelca (lurbinectedin)
8d
Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer. (PubMed, Cell Rep Med)
Interestingly, our study shows that lurbinectedin treatment upregulates MHC-I/II genes and CD8 in SCLC clinical samples. We provide mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and demonstrate that lurbinectedin treatment represents a promising therapeutic strategy to potentiate the efficacy of immunotherapy in SCLC.
Journal
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CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1)
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Zepzelca (lurbinectedin)
9d
Therapeutic drug monitoring of docetaxel administered for breast cancer in a patient receiving rifampicin and clarithromycin to treat nontuberculous mycobacteriosis: A case report. (PubMed, Mol Clin Oncol)
The patient was diagnosed as having stage IV HER2-positive breast cancer, which was treated with a regimen of trastuzumab (8 mg/kg), pertuzumab (first dose: 840 mg; second dose onward: 420 mg) and docetaxel (75 mg/m2) every 3 weeks. After 4 months of chemotherapy, the patient received complete remission. In conclusion, concomitant use of rifampicin and clarithromycin may increase the blood concentration of docetaxel.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
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HER-2 positive
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Herceptin (trastuzumab) • docetaxel • Perjeta (pertuzumab) • rifampicin
20d
Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway. (PubMed, Chin Herb Med)
Its therapeutic efficacy was comparable to, if not better than, that of Silibinin when administered at a dose of 400 mg/kg. EEIB showed significant therapeutic effects on alcohol-induced liver injury in mice, and its mechanism of action was related to the SIRT1-AMPK, nuclear factor-kappa B (NF-κB), and Nrf2 signaling pathways, in which sesquiterpenes may be the potential active ingredients.
Journal
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TNFA (Tumor Necrosis Factor-Alpha)
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Legalon (silibinin)
24d
Adequacy of the New Pediatric Isoniazid/Rifampin/Pyrazinamide (HRZ) Tablet (clinicaltrials.gov)
P=N/A, N=92, Completed, University of Florida | Recruiting --> Completed
Trial completion
28d
An Adaptive Trial to Find the Safest and Shortest TB Preventive Regimens. (clinicaltrials.gov)
P2/3, N=1800, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre | Initiation date: Oct 2024 --> Feb 2025
Trial initiation date
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rifampicin
29d
Lurbinectedin + Doxorubicin In Leiomyosarcoma (clinicaltrials.gov)
P1/2, N=62, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Jul 2025
Enrollment closed • Trial primary completion date
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doxorubicin hydrochloride • Zepzelca (lurbinectedin)
1m
Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas (clinicaltrials.gov)
P1/2, N=0, Withdrawn, University of California, San Francisco | N=70 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal • Metastases
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Zepzelca (lurbinectedin)
1m
P-RIF: Precision Rifampin Trial for Personalized Dosing (clinicaltrials.gov)
P1, N=200, Not yet recruiting, University of Virginia | Phase classification: P1/2 --> P1 | Initiation date: Jul 2024 --> Jan 2025
Phase classification • Trial initiation date
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rifampicin
2ms
In Silico Discovery of a Novel PI3Kδ Inhibitor Incorporating 3,5,7-Trihydroxychroman-4-one Targeting Diffuse Large B-Cell Lymphoma. (PubMed, Int J Mol Sci)
The results of molecular dynamics indicated that Silibinin could stably bind to PI3Kδ. Silibinin was a structurally novel 3,5,7-trihydroxychroman-4-one PI3Kδ inhibitor, providing valuable information for the subsequent discovery of PI3Kδ inhibitors.
Journal
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PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
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Legalon (silibinin)
2ms
Silibinin Suppresses Inflammatory Responses Induced by Exposure to Asian Sand Dust. (PubMed, Antioxidants (Basel))
Overall, silibinin treatment reduced the expression of p-p65NF-κB, COX-2, and p-p38 in response to ASD exposure, while increasing HO-1 expression both in vitro and in vivo. These findings suggest that silibinin mitigates pulmonary inflammation caused by ASD exposure by reducing inflammatory signaling and oxidative stress, indicating its potential as a therapeutic agent for ASD-induced pulmonary inflammation.
Journal
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TNFA (Tumor Necrosis Factor-Alpha)
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Legalon (silibinin)
2ms
New P2 trial
2ms
LINC01116-dependent upregulation of RNA polymerase I transcription drives oncogenic phenotypes in lung adenocarcinoma. (PubMed, J Transl Med)
Collectively, our findings reveal, for the first time, that LINC01116 enhances Pol I transcription by scaffolding essential transcription factors to the ribosomal DNA promoter, thereby driving oncogenic activities in LUAD. We propose the c-Myc-LINC01116-Pol I axis as a critical oncogenic pathway and a potential therapeutic target for modulating Pol I transcription in LUAD.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • LINC01116 (Long Intergenic Non-Protein Coding RNA 1116)
3ms
OpTION: Optimal Treatment for Recurrent Clostridium Difficile (clinicaltrials.gov)
P4, N=308, Completed, VA Office of Research and Development | Active, not recruiting --> Completed
Trial completion
3ms
VA INTREPID: Investigation of Rifampin to Reduce Pedal Amputations for Osteomyelitis in Diabetics (clinicaltrials.gov)
P4, N=880, Recruiting, VA Office of Research and Development | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
Trial completion date • Trial primary completion date
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rifampicin
3ms
ASTERoiD: Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI (clinicaltrials.gov)
P2/3, N=3400, Recruiting, Centers for Disease Control and Prevention | Trial completion date: Dec 2028 --> Dec 2029 | Trial primary completion date: Dec 2028 --> Dec 2029
Trial completion date • Trial primary completion date
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CD4 (CD4 Molecule)
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rifampicin
3ms
New trial
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rifampicin
3ms
Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas (clinicaltrials.gov)
P1/2, N=70, Not yet recruiting, University of California, San Francisco | Trial completion date: Jul 2027 --> Oct 2027 | Initiation date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jan 2026 --> May 2026
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
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Zepzelca (lurbinectedin)
3ms
Electrochemical detection of MMP-2 with enhanced sensitivity: Utilizing T7 RNA polymerase and CRISPR-Cas12a for neuronal studies. (PubMed, Talanta)
These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.
Journal
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MMP2 (Matrix metallopeptidase 2)
4ms
Association with TFIIIC limits MYCN localisation in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA polymerase II. (PubMed, Elife)
This increase correlates with a failure of the nuclear exosome and BRCA1, both of which are involved in nascent RNA degradation, to localise to active promoters. Our data suggest that MYCN and TFIIIC exert an censoring function in early transcription that limits promoter accumulation of inactive RNAPII and facilitates promoter-proximal degradation of nascent RNA.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
4ms
Pregnane X receptor inhibits the transdifferentiation of hepatic stellate cells by downregulating periostin expression. (PubMed, Biochem J)
This induction was attenuated upon PXR activation in hPXR-LX2 cells by treatment with the destabilization domain-stabilizing chemical Shield-1 and the human PXR ligand rifampicin...Reporter assays with the POSTN promoter showed that PXR inhibited the NF-κB-mediated transcription of POSTN. Consequently, PXR activation in HSCs is expected to inhibit transdifferentiation by downregulating POSTN expression, thereby suppressing EMT of liver cancer cells.
Journal
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TGFB1 (Transforming Growth Factor Beta 1) • COL1A1 (Collagen Type I Alpha 1 Chain) • POSTN (Periostin)
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rifampicin
4ms
CONTRol-TB: French National Cohort of Patients With Rifampicin-Resistant Tuberculosis (clinicaltrials.gov)
P=N/A, N=300, Not yet recruiting, Assistance Publique - Hôpitaux de Paris
New trial
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rifampicin
4ms
OpTION: Optimal Treatment for Recurrent Clostridium Difficile (clinicaltrials.gov)
P4, N=308, Active, not recruiting, VA Office of Research and Development | Recruiting --> Active, not recruiting | N=549 --> 308
Enrollment closed • Enrollment change
4ms
Correlations of LncRNA HNF4A-AS1 Alternative Transcripts with Liver Diseases and Drug Metabolism. (PubMed, Drug Metab Dispos)
The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment...Significance Statement This study explores the alternative transcripts of HNF4A-AS1, showing how their expression changes in different biological conditions, from various liver diseases to the growth and differentiation of hepatocytes, and drug metabolism. The generated knowledge is essential for understanding the independent roles of different transcripts from the same lncRNA in different liver diseases and drug metabolism situations.
Journal
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CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) • HNF1A (HNF1 Homeobox A)
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rifampicin
4ms
LUPER: Lurbinectedin (PM01183) Combined With Pembrolizumab in Small Cell Lung Cancer. (clinicaltrials.gov)
P1/2, N=28, Active, not recruiting, Antonio Calles Blanco | Trial completion date: Feb 2024 --> Mar 2025
Trial completion date • Combination therapy
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Keytruda (pembrolizumab) • Zepzelca (lurbinectedin)
4ms
Co-SAM: An Adaptive Multi-arm Trial to Improve Clinical Outcomes Among Children Recovering From Complicated SAM (clinicaltrials.gov)
P3, N=1266, Recruiting, Queen Mary University of London | Not yet recruiting --> Recruiting
Enrollment open
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CCL2 (Chemokine (C-C motif) ligand 2)
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rifampicin
4ms
Herb-Nanoparticle Hybrid System for Improved Oral Delivery Efficiency to Alleviate Breast Cancer Lung Metastasis. (PubMed, Int J Nanomedicine)
Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin...HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.
Journal
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TGFB1 (Transforming Growth Factor Beta 1) • MMP9 (Matrix metallopeptidase 9)
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Legalon (silibinin)
4ms
RICHH: Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria (clinicaltrials.gov)
P2, N=60, Recruiting, Children's Hospital of Philadelphia | N=30 --> 60
Enrollment change
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rifampicin
5ms
Enrollment change • Trial withdrawal • Metastases
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Bavencio (avelumab) • Zepzelca (lurbinectedin) • dexamethasone injection • ondansetron intravenous
5ms
Silibinin Induces Both Apoptosis and Necroptosis with Potential Anti-tumor Efficacy in Lung Cancer. (PubMed, Anticancer Agents Med Chem)
This study helped clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in dual induction of apoptosis and necroptosis. In particular, necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL. Our work provided an experimental basis for the research on cell death induced by SiL and revealed its possible applications for improving the management of lung cancer.
Journal
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RIPK1 (Receptor Interacting Serine/Threonine Kinase 1)
|
Legalon (silibinin)
5ms
A Short Regimen for Rifampicin-resistant Isoniazid-susceptible TB (clinicaltrials.gov)
P3, N=100, Not yet recruiting, Taipei Medical University WanFang Hospital
New P3 trial
|
rifampicin
5ms
Synthesis, Characterization, and In-Vitro Evaluation of Silibinin-loaded PEGylated Niosomal Nanoparticles: Potential Anti-Cancer Effects on SW480 Colon Cancer Cells. (PubMed, Asian Pac J Cancer Prev)
The outcomes of this study indicate the high potential of PEGylated niosomal nanoparticles for encapsulation and delivery of silibinin to cancer cells, with no negative effects on normal cells.
Preclinical • Journal • IO biomarker
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • BAX (BCL2-associated X protein)
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Legalon (silibinin)
5ms
Linnovate: A phase I/II study of safety/efficacy using lurbinectedin combined with ipilimumab and nivolumab for advanced soft tissue sarcoma (NCT05876715) - Interim analysis of phase I part (ESMO 2024)
Taken together, the data shows that (1) lurbinectedin combined with ipilimumab and nivolumab is a safe regimen with a MTD of 3.2 mg/m2 for lurbinectedin and (2) there were no serious treatment related adverse events reported. The phase II part of the study is currently open for previously untreated patient enrollment.
P1/2 data • Clinical • Metastases
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Signatera™
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Zepzelca (lurbinectedin)
5ms
An Exploratory Study of Lurbinectedin With Radiotherapy in Locally-advanced SCLC After First-line Therapy (clinicaltrials.gov)
P2, N=9, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
New P2 trial • Metastases
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Zepzelca (lurbinectedin)
5ms
Rifampicin Resistance in S. Aureus During and After Treatment for Latent Tuberculosis (clinicaltrials.gov)
P=N/A, N=100, Recruiting, Region Skane | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2026
Trial completion date • Trial primary completion date
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rifampicin
5ms
An Adaptive Trial to Find the Safest And Shortest TB Preventive Regimens. (clinicaltrials.gov)
P2/3, N=1800, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre
New P2/3 trial
|
rifampicin
5ms
New P3 trial • Combination therapy
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irinotecan • topotecan • Zepzelca (lurbinectedin)
6ms
Silibinin improved the function of T cells in peripheral blood mononuclear cells (PBMCs) co-cultured with U-87 MG cell line. (PubMed, Avicenna J Phytomed)
Interestingly, silibinin protected PBMCs against the U-87-induced suppression. Altogether, these results proposed the immunomodulatory potential of silibinin on T cells of PBMCs, as well as its partially protective effects on PBMCs against the suppression induced by U-87 MG cells.
Preclinical • Journal
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IFNG (Interferon, gamma) • TGFB1 (Transforming Growth Factor Beta 1) • SOD3 (Superoxide dismutase 3)
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Legalon (silibinin)