PMID-sentid Pub_year Sent_text compound_name comp_offset prot_official_name organism prot_offset 35614224-7 2022 We identified a small molecule, the curaxin CBL0137, which potently activates ZBP1 by triggering Z-DNA formation in cells. CBLC137 44-51 Z-DNA binding protein 1 Homo sapiens 78-82 35605992-6 2022 CBL0137-binding proteins included glycolysis enzymes (aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, phosphoglycerate kinase), and DNA-binding proteins (UMSBP2, RPA1, RPA2). CBLC137 0-7 replication protein A1 Homo sapiens 187-191 35605992-6 2022 CBL0137-binding proteins included glycolysis enzymes (aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, phosphoglycerate kinase), and DNA-binding proteins (UMSBP2, RPA1, RPA2). CBLC137 0-7 replication protein A2 Homo sapiens 193-197 35605992-10 2022 RNAi against RPA1 inhibited both DNA synthesis and mitosis, whereas RPA2 knockdown inhibited mitosis, consistent with both proteins being physiologic targets of CBL0137. CBLC137 161-168 replication protein A2 Homo sapiens 68-72 33439292-7 2021 Anti-tumor activity of CBL0137 was abrogated in CD8+ T cell depleted mice but only partially lost when natural killer or CD4+ T cells were depleted. CBLC137 23-30 CD4 antigen Mus musculus 121-124 35323988-2 2022 The curaxin CBL0137 has demonstrated promising antitumour activities in multiple cancers such as glioblastoma, acting through p53 activation, NF-kappaB inhibition and chromatin remodelling. CBLC137 12-19 tumor protein p53 Homo sapiens 126-129 35323988-3 2022 In the present study, it was revealed using Annexin-V/7-AAD apoptosis assays that CBL0137 has efficacy across several human acute leukaemia cell lines with wild-type TP53, but sensitivity is reduced in TP53-mutated subtypes. CBLC137 82-89 tumor protein p53 Homo sapiens 166-170 35323988-3 2022 In the present study, it was revealed using Annexin-V/7-AAD apoptosis assays that CBL0137 has efficacy across several human acute leukaemia cell lines with wild-type TP53, but sensitivity is reduced in TP53-mutated subtypes. CBLC137 82-89 tumor protein p53 Homo sapiens 202-206 35323988-4 2022 A heterozygous TP53 loss-of-function mutation in the KMT2A-AFF1 human RS4;11 cell line was generated, and it was demonstrated that heterozygous TP53 loss-of-function is sufficient to cause a significant reduction in CBL0137 sensitivity. CBLC137 216-223 lysine methyltransferase 2A Homo sapiens 53-58 35323988-4 2022 A heterozygous TP53 loss-of-function mutation in the KMT2A-AFF1 human RS4;11 cell line was generated, and it was demonstrated that heterozygous TP53 loss-of-function is sufficient to cause a significant reduction in CBL0137 sensitivity. CBLC137 216-223 tumor protein p53 Homo sapiens 144-148 35323988-5 2022 To the best of our knowledge, this is the first evidence to suggest a clinically significant role for functional p53 in the efficacy of CBL0137 in acute leukaemia. CBLC137 136-143 tumor protein p53 Homo sapiens 113-116 35323988-6 2022 Future CBL0137 clinical trials should include TP53 mutation screening, to establish the clinical relevance of TP53 mutations in CBL0137 efficacy. CBLC137 128-135 tumor protein p53 Homo sapiens 110-114 33853831-7 2021 Mechanistically, CBL0137 exerted anti-hedgehog activity by targeting transcription of GLI1 and GLI2, which are core transcription factors of the hedgehog pathway. CBLC137 17-24 GLI family zinc finger 1 Homo sapiens 86-90 33853831-7 2021 Mechanistically, CBL0137 exerted anti-hedgehog activity by targeting transcription of GLI1 and GLI2, which are core transcription factors of the hedgehog pathway. CBLC137 17-24 GLI family zinc finger 2 Homo sapiens 95-99 33853831-9 2021 Moreover, CBL0137 synergized with BET or CDK7 inhibitors to antagonize aberrant hedgehog pathway and growth of hedgehog-driven cancer models. CBLC137 10-17 delta/notch like EGF repeat containing Homo sapiens 34-37 35323988-0 2022 TP53 loss-of-function mutations reduce sensitivity of acute leukaemia to the curaxin CBL0137. CBLC137 85-92 tumor protein p53 Homo sapiens 0-4 33907746-7 2021 Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). CBLC137 129-140 SPT16 homolog, facilitates chromatin remodeling subunit Homo sapiens 40-47 33907746-7 2021 Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). CBLC137 142-149 SPT16 homolog, facilitates chromatin remodeling subunit Homo sapiens 40-47 33852836-3 2021 We show that CBL0137 displays profound cytotoxic activity against a panel of patient-derived DIPG cultures by restoring tumor suppressor TP53 and Rb activity. CBLC137 13-20 tumor protein p53 Homo sapiens 137-141 33852836-5 2021 The FACT subunit SPT16 is found to directly interact with H3.3K27M, and treatment with CBL0137 restores both histone H3 acetylation and trimethylation. CBLC137 87-94 SPT16 homolog, facilitates chromatin remodeling subunit Homo sapiens 17-22 33852836-6 2021 Combined treatment of CBL0137 with the histone deacetylase inhibitor panobinostat leads to inhibition of the Rb/E2F1 pathway and induction of apoptosis. CBLC137 22-29 E2F transcription factor 1 Homo sapiens 112-116 33570402-4 2021 More importantly, we found that CBL0137 greatly impairs the binding of CTCF but facilitates trapping FACT on DNA. CBLC137 32-39 CCCTC-binding factor Homo sapiens 71-75 33570402-5 2021 We revealed that CBL0137 clamps the DNA double helix that may induce a huge barrier for DNA unzipping during replication and transcription and causes the distinct binding response of CTCF and FACT on DNA. CBLC137 17-24 CCCTC-binding factor Homo sapiens 183-187 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 0-7 chemokine (C-X-C motif) receptor 3 Mus musculus 36-41 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 0-7 chemokine (C-X-C motif) ligand 10 Mus musculus 88-125 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 0-7 chemokine (C-X-C motif) ligand 10 Mus musculus 127-132 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 0-7 chemokine (C-X-C motif) ligand 10 Mus musculus 155-160 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 0-7 chemokine (C-X-C motif) receptor 3 Mus musculus 161-166 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 176-183 chemokine (C-X-C motif) ligand 10 Mus musculus 88-125 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 176-183 chemokine (C-X-C motif) ligand 10 Mus musculus 155-160 33439292-9 2021 CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-gamma-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. CBLC137 176-183 chemokine (C-X-C motif) receptor 3 Mus musculus 161-166 29440145-0 2018 The FACT inhibitor CBL0137 Synergizes with Cisplatin in Small-Cell Lung Cancer by Increasing NOTCH1 Expression and Targeting Tumor-Initiating Cells. CBLC137 19-26 notch 1 Mus musculus 93-99 33268769-0 2020 Effective inhibition of MYC-amplified group 3 medulloblastoma by FACT-targeted curaxin drug CBL0137. CBLC137 92-99 MYC proto-oncogene, bHLH transcription factor Homo sapiens 24-27 32202904-10 2020 Results showed that the expression of p-p53, p53, Bax and PUMA was upregulated after CBL0137 administration. CBLC137 85-92 tumor protein p53 Homo sapiens 40-43 32202904-10 2020 Results showed that the expression of p-p53, p53, Bax and PUMA was upregulated after CBL0137 administration. CBLC137 85-92 tumor protein p53 Homo sapiens 45-48 32202904-13 2020 And the protein of apoptosis-related proteins including PARP, caspase-3, caspase-7, caspase-8, and caspase-9 were increased in CBL group compared with NC group (P < 0.05), while the NF-kappaB, p-NF-kappaB and p-AKT expression levels were significantly downregulated following CBL0137 treatment (P < 0.05). CBLC137 276-283 Cbl proto-oncogene Homo sapiens 127-130 30989696-3 2019 Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor-alpha-mediated reactivation of latently infected HIV-1cell lines. CBLC137 29-36 tumor necrosis factor Homo sapiens 76-103 25402820-8 2014 In mice, CBL0137 was effective against several PDA models, including orthotopic gemcitabine resistant PANC-1 model and patient derived xenografts, in which CBL0137 anti-tumor effect correlated with overexpression of FACT. CBLC137 9-16 pancreas protein 1 Mus musculus 102-108 27370399-3 2017 One such clinical-stage drug candidate, CBL0137, is a curaxin, small molecules which simultaneously downregulate nuclear factor-kappaB (NF-kB) and activate p53 by inactivating the chromatin remodeling complex, Facilitates Chromatin Transcription (FACT). CBLC137 40-47 tumor protein p53 Homo sapiens 156-159 27370399-8 2017 CBL0137 induced loss of chromatin-unbound FACT, activated p53, inhibited NF-kB-dependent transcription, and was toxic to GBM cells. CBLC137 0-7 tumor protein p53 Homo sapiens 58-61 26537256-5 2015 CBL0137 exhibited strong synergy with standard chemotherapy by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN-amplified neuroblastoma cells and suggesting a treatment strategy for MYCN-driven neuroblastoma. CBLC137 0-7 MYCN proto-oncogene, bHLH transcription factor Homo sapiens 168-172 26537256-5 2015 CBL0137 exhibited strong synergy with standard chemotherapy by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN-amplified neuroblastoma cells and suggesting a treatment strategy for MYCN-driven neuroblastoma. CBLC137 0-7 MYCN proto-oncogene, bHLH transcription factor Homo sapiens 243-247 25402820-9 2014 Moreover, we observed synergy of CBL0137 with gemcitabine which may be explained by the ability of CBL0137 to inhibit several transcriptional programs induced by gemcitabine, including NF-kappaB response and expression of ribonucleotide reductase, one of the targets of gemcitabine in cells. CBLC137 33-40 nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 Mus musculus 185-194 22689915-3 2012 In tumor cells, Curaxin-137 inhibits NF-kappaB- and HSF1-dependent transcription (prosurvival pathways) and activates p53 (a proapoptotic pathway) without inducing DNA damage. CBLC137 16-27 heat shock factor 1 Mus musculus 52-56 22689915-3 2012 In tumor cells, Curaxin-137 inhibits NF-kappaB- and HSF1-dependent transcription (prosurvival pathways) and activates p53 (a proapoptotic pathway) without inducing DNA damage. CBLC137 16-27 transformation related protein 53, pseudogene Mus musculus 118-121 22689915-6 2012 On the basis of this background, we tested whether Curaxin-137 could suppress tumorigenesis in MMTV-neu transgenic mice, which spontaneously develop mammary carcinoma due to steroid receptor-regulated expression of the Her2 proto-oncogene. CBLC137 51-62 erb-b2 receptor tyrosine kinase 2 Mus musculus 219-223 22689915-7 2012 We found that chronic administration of Curaxin-137 in a preventive regimen to MMTV-neu mice did not cause any detectable changes in normal organs and tissues, yet inhibited tumor onset, delayed tumor progression, and prolonged survival of mice in a dose-dependent manner. CBLC137 40-51 erb-b2 receptor tyrosine kinase 2 Mus musculus 84-87 22689915-8 2012 Curaxin-137 induced changes in FACT, altered NF-kappaB localization, and activated p53 in tumor cells as expected from its defined mechanism of action. CBLC137 0-11 transformation related protein 53, pseudogene Mus musculus 83-86