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DRUG:

BIBR1532

i
Other names: BIBR1532, BIBR 1532
Company:
Boehringer Ingelheim
Drug class:
Telomerase inhibitor
27d
The mechanism of NF-κB-TERT feedback regulation of granulosa cell apoptosis in PCOS rats. (PubMed, PLoS One)
Using letrozole and a high-fat diet, a PCOS rat model was established, along with a Lipopolysaccharide (LPS) -treated KGN cell inflammation model was established. NF-κB and TERT inhibitors (BAY 11-7082 and BIBR1532) were then administered to LPS-induced KGN cells...LPS-treated KGN cells demonstrated increased expression of inflammatory and pro-apoptotic factors, later restored post-treatment with NF-κB and TERT inhibitors (P are all less than 0.05). In conclusion, TERT may induce granulosa cell apoptosis by participating in the regulation of the NF-κB signaling pathway, thereby mediating the chronic inflammatory response of PCOS through downstream inflammatory factors IL-6 and TNF-α.
Preclinical • Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • TERT (Telomerase Reverse Transcriptase) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3)
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letrozole • BIBR1532 • Bay11-7082
2ms
Muti-target rationale design of novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates as telomerase/JAK1/STAT3/TLR4 inhibitors: In vitro and in vivo investigations. (PubMed, Bioorg Chem)
In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem...Compound 4l represented a very promising JAK1 inhibitory potential with a 0.46-fold change, compared to that of pacritinib reference standard (0.33-fold change). Besides, it showed a superior STAT3-inhibitory potential with a 0.22-fold change compared to sorafenib (0.33-fold change). Additionally, compound 4l downregulated TLR4 protein expression by 0.81-fold change compared to that of resatorvid (0.29-fold change)...Remarkably, compound 4l led to prominent reductions in tumor size and mass. Concurrent enhancements in biochemical, hematologic, histopathologic, and immunohistochemical parameters further confirmed the suppression of angiogenesis and inflammation, elucidating additional mechanisms by which compound 4l exerts its anticancer effects.
Preclinical • Journal
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JAK1 (Janus Kinase 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TLR4 (Toll Like Receptor 4)
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sorafenib • Vonjo (pacritinib) • BIBR1532
4ms
Telomerase and mitochondria inhibition promote apoptosis and TET2 and ANMT3a expression in triple negative breast cancer cell lines. (PubMed, Bioimpacts)
In addition, combination treatment was better than BIBR1532 and tigecycline alone. The inhibition of telomerase and mitochondria respiration caused intrinsic- and extrinsic- apoptosis and increased DNMT3a and TET2 expression and it could be utilized in breast cancer treatment.
Preclinical • Journal
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TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • TERT (Telomerase Reverse Transcriptase) • TET2 (Tet Methylcytosine Dioxygenase 2)
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BIBR1532
6ms
LKB1 inhibits telomerase activity resulting in cellular senescence through histone lactylation in lung adenocarcinoma. (PubMed, Cancer Lett)
The telomerase inhibitor BIBR1532 was beneficial for achieving the optimum curative effect of traditional chemotherapeutic drugs accompanied by the glycolysis inhibitor 2DG. These data reveal a new mechanism by which LKB1 regulates telomerase activity through lactylation-dependent transcriptional inhibition, and therefore, provide new insights into the effects of LKB1-mediated senescence in lung adenocarcinoma. Our research has opened up new possibilities for the creation of new cancer treatments.
Journal
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STK11 (Serine/threonine kinase 11) • TERT (Telomerase Reverse Transcriptase)
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BIBR1532
8ms
Therapeutic targeting of telomerase ameliorates experimental choroidal neovascularization. (PubMed, Biochim Biophys Acta Mol Basis Dis)
Telomerase inhibition with BIBR 1532 suppressed induction of multiple cytokines and growth factors critical for neovascularization. In conclusion, our study identifies telomerase as a promising therapeutic target for treating neovascular disease of the eye and thus provides a proof of principle for further exploration of telomerase inhibition as a novel treatment strategy for nvAMD.
Journal
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TERT (Telomerase Reverse Transcriptase)
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BIBR1532
10ms
Role of p53 transcription factor in determining the efficacy of telomerase inhibitors in cancer treatment. (PubMed, Life Sci)
In summary, we demonstrate that acute anti-cancer effects of MST-312 are dependent on p53 expression. Hence, it is important to consider the p53 expression status in cancer cells when selecting and administering telomerase inhibitors.
Journal
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CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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TP53 expression
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BIBR1532
1year
BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity. (PubMed, PeerJ)
Further experiments were conducted to evaluate the synergistic effects of BIBR1532 and doxorubicin (Dox) or bortezomib (Bor). BIBR1532 inhibits proliferation and promotes apoptosis in MM cells by inhibiting telomerase activity. Additionally, BIBR1532 combined with Dox or Bor exhibited synergistic effects, indicating that BIBR1532 may be a novel medicine for the treatment of MM.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BCL2L1 (BCL2-like 1) • BIRC5 (Baculoviral IAP repeat containing 5)
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MYC expression • BIRC5 expression
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bortezomib • doxorubicin hydrochloride • BIBR1532
1year
Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure. (PubMed, J Environ Sci Health C Toxicol Carcinog)
BIBR 1532, an inhibitor targeting TERT, partially reduced colony formation and TL for chronical Cro-Met-5A, while BIBR 1532 reduced TL but had no effect on colony formation for chronical Cro-Met-5A. Therefore, SETD2 deficient mesothelial cells are susceptible to malignant transformation during chronical crocidolite exposure, and TERT-dependent TL modification likely partially drives SETD2 loss-mediated early onset of mesothelial malignant transformation.
Journal
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TERT (Telomerase Reverse Transcriptase) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
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BIBR1532
over1year
Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach. (PubMed, Cancers (Basel))
The combination of BIBR1532 with antineoplastic drugs (cyclophosphamide or fludarabine) significantly reduced xenografted cells' proliferation rate compared to monotherapy in the zebrafish xenograft model. Overall, these findings indicate that short-term inhibition of TERT impairs cell growth through the downregulation of MYC via NF-κB signalling and supports the use of TERT inhibitors in combination with antineoplastic drugs as an efficient anticancer strategy.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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BRAF wild-type
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cyclophosphamide • fludarabine IV • BIBR1532
over1year
Evaluation of the anticancer effect of telomerase inhibitor BIBR1532 in anaplastic thyroid cancer in terms of apoptosis, migration and cell cycle. (PubMed, Med Oncol)
BIBR1532 treatment resulted in an increase in BAX and p16 proteins, and a decrease in concentration of BCL-2 protein compared to untreated group. Targeting TERT with BIBR1532 as a mono drug or using of BIBR1532 at "priming stage" prior to chemotherapy treatment in ATC may present a novel and promising treatment strategy.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BCL2L11 (BCL2 Like 11) • CASP8 (Caspase 8) • CCND2 (Cyclin D2) • XIAP (X-Linked Inhibitor Of Apoptosis) • TNFSF10 (TNF Superfamily Member 10) • ANXA5 (Annexin A5)
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BIBR1532
almost2years
The Effect of Telomerase Inhibition on NK Cell Activity in Acute Myeloid Leukemia. (PubMed, Adv Pharm Bull)
According to these findings, BIBR1532 affected the final differentiation of NK cells. The results revealed that telomerase inhibitor drugs suppress cancer cell progression in a NK cells-independent process.
Journal
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CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • ENG (Endoglin) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
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BIBR1532
almost2years
A combination of telomerase inhibition and NK cell therapy increased breast cancer cell line apoptosis. (PubMed, Biochem Biophys Res Commun)
In this study, we inhibited telomerase (hTERT) with BIBR1532, in stimulating NK cell cytotoxicity against breast cancer cells...In conclusion, telomerase suppression makes breast cancer cells more sensitive to NK cell therapy. Consequently, the combination of telomerase inhibition and NK cells can be useful in the treatment of breast cancer cells.
Preclinical • Journal
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TERT (Telomerase Reverse Transcriptase) • BAX (BCL2-associated X protein)
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BAX expression
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BIBR1532
2years
Consecutive Inhibition of Telomerase and Alternative Lengthening Pathway Promotes Hodgkin's Lymphoma Cell Death. (PubMed, Biomedicines)
We report that the inhibition of telomerase using BIBR1532 followed by ALT inhibition, using trabectedin, caused a decrease of greater than 90% in cell viability in three patient-derived HL cell lines. Our results suggest that HL cells are most vulnerable to the consecutive inhibition of telomerase followed by ALT inhibition.
Journal
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TERF1 (Telomeric Repeat Binding Factor 1)
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Yondelis (trabectedin) • BIBR1532
over2years
Telomerase inhibition on acute myeloid leukemia stem cell induced apoptosis with both intrinsic and extrinsic pathways. (PubMed, Life Sci)
In total, it was revealed that TI induced apoptosis through intrinsic, extrinsic, and p53 pathways and increased the expression of DNMT3a and TET2 epigenetic markers.
Journal
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DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule)
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BIBR1532
3years
Combination of resveratrol and BIBR1532 inhibits proliferation of colon cancer cells by repressing expression of LncRNAs. (PubMed, Med Oncol)
In silico analysis revealed that LncRNAs whose expression levels were decreased after treatments were associated with CRC. Resveratrol, BIBR1532, or their combination may have anti-proliferative effect on colorectal cancer cells through repressing expression of LncRNAs that are involved in progression of CRC.
Journal
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HOTAIR (HOX Transcript Antisense RNA) • PVT1 (Pvt1 Oncogene)
|
BIBR1532
over3years
Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells. (PubMed, Cancers (Basel))
Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo...In the present study, we demonstrate that telomerase regulation is critical for the "stemness" maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.
Journal
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KLF4 (Kruppel-like factor 4) • SOX2 • NANOG (Nanog Homeobox)
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BIBR1532
almost4years
The Small Molecule BIBR1532 Exerts Potential Anti-cancer Activities in Preclinical Models of Feline Oral Squamous Cell Carcinoma Through Inhibition of Telomerase Activity and Down-Regulation of TERT. (PubMed, Front Vet Sci)
Moreover, BIBR1532 diminished the expression of TERT and its transcriptional activator cMyc, resulting in the down-regulation of epidermal growth factor receptor (EGFR), phospho-ERK/ERK ratio, and matrix metalloproteinases (MMPs)-1/-2 and-9, likely as a consequence of an impairment of TERT extra-telomeric functions. Taken together, our data suggest that BIBR1532 exerts multiple anti-cancer activities in FOSCC by inhibiting telomerase pathway and interfering with signaling routes involved in cell proliferation, cell survival, and invasion, paving the way for future translational studies aimed at evaluating its possible employment in the treatment of this severe tumor of cats.
Preclinical • Journal • IO biomarker
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EGFR (Epidermal growth factor receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • TERT (Telomerase Reverse Transcriptase) • BIRC5 (Baculoviral IAP repeat containing 5)
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BIBR1532