Results and prospects of development of new polyphenolic drugs for cancer patients

Anisimov, Vladimir N.; Larsen, Stig; Lofberg, Stig; Балдуева, Ирина; Malek, Anastasia; Nielsen, Tea Kirkegaard; Fedoros, Elena I.; Perminova, Irina V.; Drobyshev, Evgenii; Быков, В. Н.; Panchenko, Andrey; Scherbakov, Alexander M.; Belyaеv, Alexey M.

doi:10.18632/oncotarget.22307

Cited by 9 publications

(6 citation statements)

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“…The majority of the identified targets belong to neurotransmitters receptors, ligand-gated ion channels and transporters, which are expressed in central and peripheral nervous systems. Given that drugs, which contain BP-Cx-1 ligand, are developed for antitumor therapy or as supportive care for cancer patients [ 35 ], of particular interest was to identify molecular targets, which are involved in modulation of inflammation and immune response.…”

Section: Resultsmentioning

confidence: 99%

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Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro

et al. 2018

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Identification of molecular targets and mechanism of action is always a challenge, in particular – for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties. The results of diversity assay demonstrate that BP-Cx-1 has multiple biological effects on neurotransmitters receptors, ligand-gated ion channels and transporters. Of particular importance is that the major part of identified molecular targets are involved in modulation of inflammation and immune response and might be related to tumorigenesis. Characterization of molecular composition of BP-Cx-1 with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and subsequent identification of possible active components by searching for molecular matches in silico in ChEMBL indicated polyphenolic components, nominally, flavonoids, sapogenins, phenanthrenes, as the major carriers of biological activity of BP-Cx-1. In vitro and in silico target screening yielded overlapping lists of proteins: adenosine receptors, dopamine receptor DRD4, glucocorticoid receptor, serotonin receptor 5-HT1, prostaglandin receptors, muscarinic cholinergic receptor, GABAA receptor. The pleiotropic molecular activities of polyphenolic components are beneficial in treatment of multifactorial disorders such as diseases associated with chronic inflammation and cancer.

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Section: Resultsmentioning

confidence: 99%

“…Earlier reports demonstrated that BP-Cx-1, when administered intravenously, was able to traverse the blood brain barrier [ 35 ]. Activity of BP-Cx-1 towards GABAA/BZD receptors and a lack of effect towards opioid receptors ( Supplementary File 1 ) are demonstrated by the results of the present study.…”

Section: Resultsmentioning

confidence: 99%

Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro

et al. 2018

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“…BP-C1 was developed for the treatment of MBC and pancreatic cancer. The safety and efficacy of cisplatin, carboplatin, and BP-C1 have been compared in mice with Ehrlich tumors 32. The three drugs stimulated apoptosis in tumor tissue, and the specific activity of BP-C1 was similar to that of an equimolar dose of carboplatin but with lower toxicity.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of BP-C1 in metastatic breast cancer: a Phase II, randomized, double-blind, and placebo-controlled Thai multi-center study

Butthongkomvong

Raunroadroong

Sorrarichingchai

et al. 2019

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AimsThe aim of this study was to compare the efficacy and tolerability of BP-C1 vs equal-looking placebo in metastatic breast cancer.Materials and methodsA randomized, double-blind, placebo-controlled multi-center study with a semicross-over design was performed. Sixteen patients received daily intramuscular injection of 0.035 mg/kg bodyweight of BP-C1 and 15 patients received equal-looking placebo for 32 days. After 32 days, the placebo patients crossed to BP-C1 with the last observation in the placebo period as baseline. The status of receptors including estrogen receptor (ER), progesterone receptor (PtR), and human EGF receptor 2 (HER2) was analyzed prior to inclusion in the study. Thoracoabdominal CT scan was blindly analyzed by the same independent radiologist in accordance with the RECIST criteria 1.1. Toxicity was assessed according to the NCI Bethesda Version 2.0 (CTC-NCI), and the quality of life (QOL) was assessed according to European Organization for the Research and Treatment of Cancer QOL-C30 and QOL-BR23.ResultsThe sum of target lesion diameters (sum lesions) after 32 days of treatment increased by 8.9% (P=0.08) in the BP-C1 arm compared to 37.6% (P<0.001) in placebo patients. Twelve of the 15 placebo patients subsequently had BP-C1 treatment. The increase in sum lesions was 3.5% in these patients. The sum of CTC-NCI was increased 18.7% in the BP-C1 arm (P=0.38) compared to 50.9% (P=0.04) in placebo patients. Four mild/moderate adverse events (AEs) present in BP-C1. Two mild/moderate AEs and one severe AE present in placebo. The QOL benchmarks “breast cancer problems last week”, “sexual interest and activity last 4 weeks”, and “breast cancer-related pain and discomfort last week” were stable in the BP-C1 arm but deteriorated in placebo patients. The sum lesions increased significantly in ER+ (P=0.02) and PtR+ (P=0.03) but not in HER2+. The increase in sum lesions significantly decreased (P=0.02) with an increasing number of negative receptors.ConclusionA total of 32 days of BP-C1 treatment inhibited cancer growth and was well tolerated with few and mainly mild AEs. The efficacy of BP-C1 was superior in receptor-negative patients.ClinicalTrials.gov IdentifierNCT03603197.

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“…BP-Cx-1, novel polyphenolic ligand, is a water-soluble fraction of wood lignin and is the platform for a portfolio of innovative pharmacological products such as antineoplastic agent BP-C1, radiomitigator BP-C2 and geroprotective composition BP-C3 [1]. In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenathrenes etc.)…”

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Novel polyphenolic ligand of BP-Cx family drugs: cell distribution and mechanism of action

Fedoros¹,

Badun²,

Grozdova³

et al. 2019

Book of Abstracts. Fifth International Conference of CIS IHSS on Humic Innovative Technologies «Humic Substances and Living Sys

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Results and prospects of development of new polyphenolic drugs for cancer patients

Cited by 9 publications

References 0 publications

Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro

Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro

Efficacy and tolerability of BP-C1 in metastatic breast cancer: a Phase II, randomized, double-blind, and placebo-controlled Thai multi-center study

Novel polyphenolic ligand of BP-Cx family drugs: cell distribution and mechanism of action

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