CIGB-300 / Center for Genetic Engineering and Biotechnology - LARVOL DELTA

Time- and dose-dependent effects of CIGB-300 on the proteome of lung squamous cell carcinoma. (PubMed, Biol Chem) - "Likewise, we observed a consistent downregulation of different proteins that had been already reported to be inhibited by CIGB-300 in lung adenocarcinoma and acute myeloid leukemia. Overall, our proteomics-guided strategy based on time and drug dose served to uncover novel clues supporting the CIGB-300 cytotoxic effect and also to identify putative pharmacodynamic biomarkers in NSCLC."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

CIGB-300 internalizes and impairs viability of NSCLC cells lacking actionable targets by inhibiting casein kinase-2 signaling. (PubMed, Sci Rep) - "Finally, intravenous injection of CIGB-300 in a cell line-based xenograft corroborated CIGB-300's anti-tumor effects and suggested concurrent in situ reductions of CSNK2ɑ subunit and downstream RPS6s235/236 phosphorylation. Overall, CIGB-300 therapeutic hypothesis and antineoplastic effects demonstrated herein, further support the evaluation of this clinical-grade CK2 inhibitor in advanced NSCLC with limited therapeutic options."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • CDC37 • EGFR • ROS1

"Phosphoproteomic quantification based on phosphopeptide intensity or occupancy? An evaluation based on casein kinase 2 downstream effects". (PubMed, J Proteomics) - "The phosphoproteomic profile modulated in two AML cell lines after CK2 inhibition with CIGB-300 or CX-4945 is shown. A low overlap between the phosphoproteomes quantified by intensity and occupancy was obtained illustrating that new developments in proteomics techniques are needed to improve the performance of the occupancy approach. Even in such context, results indicate that occupancy quantification performs better than phosphorylation quantification based on intensity reinforcing the importance of such quantification approach to describe phosphoproteomic data."

Journal • Acute Myelogenous Leukemia

NPM promotes hepatotoxin-induced fibrosis by inhibiting ROS-induced apoptosis of hepatic stellate cells and upregulating lncMIAT-induced TGF-β2. (PubMed, Cell Death Dis) - "Inhibition of NPM or application of NPM inhibitor CIGB300 remarkably attenuated liver fibrosis. NPM serves a potential new drug target for liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • MIR16 • NPM1 • TGFB1

Gene expression profiling unveils the temporal dynamics of CIGB-300-regulated transcriptome in AML cell lines. (PubMed, BMC Genomics) - "We explored for the first time the temporal dynamics of the gene expression profile regulated by CIGB-300 which, along with the antiproliferative mechanism, can stimulate immune responses by increasing immunomodulatory cytokines. We provided fresh molecular clues concerning the antiproliferative effect of CIGB-300 in two relevant AML backgrounds."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Leukemia • Oncology • CDKN1A • CSF1 • TNFA

CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model. (PubMed, Biomedicines) - "The down-regulation of both phosphorylation and protein levels of the ribonuclear protein S6 (RPS6) was observed 48 h post treatment. Altogether, we have found that NCI-H460 cells are the most CIGB-300-sensitive solid tumor cell line described so far, and also, the findings we provide here uncover novel features linked to CK2 targeting by the CIGB-300 anticancer peptide."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RPS6

CIGB-300 Peptide Targets the CK2 Phospho-Acceptor Domain on Human Papillomavirus E7 and Disrupts the Retinoblastoma (RB) Complex in Cervical Cancer Cells. (PubMed, Viruses) - "However, the targeting of E7 phosphorylation by CIGB-300 seemed to be dispensable for the induction of cell death in HPV-18 cervical cancer-derived C4-1 cells. These findings unveil novel molecular clues to the means by which CIGB-300 triggers cell death in cervical cancer cells."

Journal • Cervical Cancer • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor

CIGB-300-Regulated Proteome Reveals Common and Tailored Response Patterns of AML Cells to CK2 Inhibition. (PubMed, Front Mol Biosci) - "Thus, oxidative stress might play a relevant role on CIGB-300-induced apoptosis in HL-60 but not in OCI-AML3 cells. Importantly, these findings provide first-hand insights concerning the CIGB-300 antileukemic effect and draw attention to the existence of both common and tailored response patterns triggered by CK2 inhibition in different AML backgrounds, a phenomenon of particular relevance with regard to the pharmacologic blockade of CK2 and personalized medicine."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach. (PubMed, Mol Med) - "Furthermore, we provided evidence of how CIGB-300 may participate in the attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders. Our computational analysis proposes putative molecular mechanisms that support the antiviral activity of CIGB-300."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300. (PubMed, Biomedicines) - "However, in vivo pull-down experiments and phosphoproteomic analysis evidenced that CIGB-300 targeted the CK2α catalytic subunit, different ribosomal proteins, and inhibited the phosphorylation of a common CK2 substrates array among both AML backgrounds. Remarkably, our results not only provide cellular and molecular insights unveiling the complexity of the CIGB-300 anti-leukemic effect in AML cells but also reinforce the rationale behind the pharmacologic blockade of protein kinase CK2 for AML-targeted therapy."

Clinical • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • NPM1

Tuning the Anti-Angiogenic Effect of the P15 Peptide Using Cyclic Trypsin Inhibitor Scaffolds. (PubMed, ACS Chem Biol) - "A novel proapoptotic peptide, CIGB-300 (P15-Tat), has been shown to be involved in the casein kinase II phosphorylation pathway, conferring it with antiangiogenic activity...Overall, the results show the value of P15 being engineered into cyclic trypsin inhibitor scaffolds for improving antiangiogenic activity and stability. More broadly, the study highlights the versatility of cyclic peptide frameworks in drug design for antiangiogenic therapies."

Journal • Oncology

Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization. (PubMed, Sci Rep) - "The present preclinical study establishes for the first time the efficacy of CIGB-300 on breast cancer. These encouraging results suggest that CIGB-300 could be used for the management of breast cancer as an adjuvant therapy after surgery, limiting tumor metastatic spread and thus protecting the patient from distant recurrence."

Journal • Preclinical • Breast Cancer • Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization (AACR-II 2020) - "We evaluated the effects of the combination of CIGB-300 and cisplatin on cell viability and apoptosis. The present preclinical study establishes for the first time the efficacy of CIGB-300 on breast cancer. These encouraging results suggest that CIGB-300 could be used for the management of breast cancer as an adjuvant therapy after surgery, limiting tumor metastatic spread and thus protecting the patient from distant recurrence."

IO Biomarker • Preclinical • Breast Cancer • Oncology • Solid Tumor • BCL2

Clinical-Grade Peptide-Based Inhibition of CK2 Blocks Viability and Proliferation of T-ALL Cells and Counteracts IL-7 Stimulation and Stromal Support. (PubMed, Cancers (Basel)) - "In the context of IL-7 stimulation, CIGB-300 blocks janus kinase / signal transducer and activator of transcription (JAK/STAT) signaling pathway in T-ALL cells. Altogether, our results strengthen the case for anti-CK2 therapeutic intervention in T-ALL, demonstrating that CIGB-300 (given its ability to circumvent the effects of pro-leukemic microenvironmental cues) may be a valid tool for clinical intervention in this aggressive malignancy."

Clinical • Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • IL7 • NPM1 • PTEN

CIGB-300 anticancer peptide regulates the protein kinase CK2-dependent phosphoproteome. (PubMed, Mol Cell Biochem) - "Altogether, we provided here the first evidence for a direct impairment of CK2 enzymatic activity by CIGB-300. Of note, both CK2-mediated inhibitory mechanisms of this anticancer peptide (i.e., substrate- and enzyme-binding mechanism) may run in parallel in tumor cells and help to explain the different anti-neoplastic effects exerted by CIGB-300 in preclinical cancer models."

Journal • Oncology