Delving into the Latest Updates on CIGB-300 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

CIGB 300, CIGB-325, CIGB325

+ [3]

Target

CK2

Mechanism

CK2 inhibitors(Casein kinase II inhibitors)

Therapeutic Areas

NeoplasmsUrogenital DiseasesRespiratory Diseases

Active Indication

Uterine Cervical CancerLung Cancer

Inactive Indication

Acute Myeloid LeukemiaCervical Squamous Cell CarcinomaCondylomata Acuminata+ [4]

Originator Organization

Centro de Ingenieria Genetica y Biotecnologia

Active Organization

Centro de Ingenieria Genetica y Biotecnologia

Inactive Organization

Laboratorio Elea Phoenix SA

Drug Highest PhasePhase 2/3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC127H215N53O30S3

InChIKeyRNELHWXSRSKXRD-QNKYCTLBSA-N

CAS Registry1072877-99-6

Gene Sequence

Sequence Code 530506658

Quantitative phosphoproteomic data has mostly been reported from experiments comparing relative phosphopeptides intensities in two or more different conditions, while the ideal parameter to compare is phosphopeptides occupancies. This term is scarcely used and therefore barely implemented in phosphoproteomics studies, and this should be of concern for the scientific journals. In order to demonstrate the relevance of this issue, here we show how the method of choice affects the interpretation of the data. The phosphoproteomic profile modulated in two AML cell lines after CK2 inhibition with CIGB-300 or CX-4945 is shown. Following the downstream action of CK2 the phosphosite intensity and occupancy results were compared to validate the best approach for quantitative phosphoproteomic studies. Even when the total number of quantified phosphopeptides was higher by using the intensity calculation, in all the cases the percent of CK2 consensus sequences which were down-regulated in response to CK2 inhibition was higher using the phosphosite occupancy quantification. To note, a high number of CK2 consensus sequences was found down-regulated with at least a 10% or 15% of phosphosite occupancy variation illustrating that low thresholds of occupancy modulation might be indicative of biological effect. Additionally, several biological processes only appear significantly over-represented in the phosphoproteome quantified by occupancy. The functional enrichment analysis per ranges of occupancy variations also illustrated clear differences among AML cell lines subjected to CK2 inhibition by CX-4945. 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.

30 Aug 2023·Cell death & disease

NPM promotes hepatotoxin-induced fibrosis by inhibiting ROS-induced apoptosis of hepatic stellate cells and upregulating lncMIAT-induced TGF-β2.

Article

Author: Shi, Song-Lin ; Li, Shuang ; Ding, Xue ; Zhu, Xin-Le ; Liu, Kuan-Can ; Yang, Qiong ; Yang, Ling ; Li, Huan ; Deng, Xiao-Ling ; Zhang, Yu-Jun ; Wei, Yong-Gui ; Feng, Xian ; Xu, Dong-Hui

Liver fibrosis is caused by a variety of chronic liver injuries and has caused significant morbidity and mortality in the world with increasing tendency. Elucidation of the molecular mechanism of liver fibrosis is the basis for intervention of this pathological process and drug development. Nucleophosmin (NPM) is a widely expressed nucleolar phosphorylated protein, which is particularly important for cell proliferation, differentiation and survival. The biological role of NPM in liver fibrosis remains unknown. Here we show that NPM promotes liver fibrosis through multiple pathways. Our study found that NPM was up-regulated in cirrhosis tissues and activated in hepatic stellate cells (HSCs). NPM inhibition reduced liver fibrosis markers expression in HSCs and inhibited the HSCs proliferation and migration. In mice model, NPM knockdown in HSCs or application of specific NPM inhibitor can remarkably attenuate hepatic fibrosis. Mechanistic analysis showed that NPM promotes hepatic fibrosis by inhibiting HSCs apoptosis through Akt/ROS pathway and by upregulating TGF-β2 through Akt-induced lncMIAT. LncMIAT up-regulated TGF-β2 mRNA by competitively sponging miR-16-5p. In response to liver injury, hepatocytes, Kupffer cells and HSCs up-regulated NPM to increase TGF-β2 secretion to activate HSCs in a paracrine or autocrine manner, leading to increased liver fibrosis. Our study demonstrated that NPM regulated hepatotoxin-induced fibrosis through Akt/ROS-induced apoptosis of HSCs and via the Akt/lncMIAT-up-regulated TGF-β2. Inhibition of NPM or application of NPM inhibitor CIGB300 remarkably attenuated liver fibrosis. NPM serves a potential new drug target for liver fibrosis.

04 Jul 2023·BMC genomics

Gene expression profiling unveils the temporal dynamics of CIGB-300-regulated transcriptome in AML cell lines.

Article

Author: Rosales, Ailenis ; Vázquez-Blomquist, Dania ; Pérez, George V ; Rosales, Mauro ; Perera, Yasser ; Perea, Silvio E ; Palenzuela, Daniel ; Ramón, Ailyn C

BACKGROUND:

Protein kinase CK2 activity is implicated in the pathogenesis of various hematological malignancies like Acute Myeloid Leukemia (AML) that remains challenging concerning treatment. This kinase has emerged as an attractive molecular target in therapeutic. Antitumoral peptide CIGB-300 blocks CK2 phospho-acceptor sites on their substrates but it also binds to CK2α catalytic subunit. Previous proteomic and phosphoproteomic experiments showed molecular and cellular processes with relevance for the peptide action in diverse AML backgrounds but earlier transcriptional level events might also support the CIGB-300 anti-leukemic effect. Here we used a Clariom S HT assay for gene expression profiling to study the molecular events supporting the anti-leukemic effect of CIGB-300 peptide on HL-60 and OCI-AML3 cell lines.

RESULTS:

We found 183 and 802 genes appeared significantly modulated in HL-60 cells at 30 min and 3 h of incubation with CIGB-300 for p < 0.01 and FC > = │1.5│, respectively; while 221 and 332 genes appeared modulated in OCI-AML3 cells. Importantly, functional enrichment analysis evidenced that genes and transcription factors related to apoptosis, cell cycle, leukocyte differentiation, signaling by cytokines/interleukins, and NF-kB, TNF signaling pathways were significantly represented in AML cells transcriptomic profiles. The influence of CIGB-300 on these biological processes and pathways is dependent on the cellular background, in the first place, and treatment duration. Of note, the impact of the peptide on NF-kB signaling was corroborated by the quantification of selected NF-kB target genes, as well as the measurement of p50 binding activity and soluble TNF-α induction. Quantification of CSF1/M-CSF and CDKN1A/P21 by qPCR supports peptide effects on differentiation and cell cycle.

CONCLUSIONS:

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.

100 Deals associated with CIGB-300

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Condylomata Acuminata	Phase 3	AR	Laboratorio Elea Phoenix SA	01 Jun 2010
Uterine Cervical Cancer	Phase 3	CU	Centro de Ingenieria Genetica y Biotecnologia	-
COVID-19	Phase 2	CU	Centro de Ingenieria Genetica y Biotecnologia	01 Jun 2020
Acute Myeloid Leukemia	Phase 2	CU	Centro de Ingenieria Genetica y Biotecnologia	07 Dec 2012
Myelodysplastic Syndromes	Phase 2	CU	Centro de Ingenieria Genetica y Biotecnologia	06 Dec 2012
Cervical Squamous Cell Carcinoma	Phase 2	AR	Laboratorio Elea Phoenix SA	01 May 2011
Squamous Cell Carcinoma	Phase 2	AR	Laboratorio Elea Phoenix SA	01 May 2011
Uterine Cervix Adenocarcinoma	Phase 2	AR	Laboratorio Elea Phoenix SA	01 May 2011
Lung Cancer	Phase 1	CU	Centro de Ingenieria Genetica y Biotecnologia	-