CC-671 / BMS - LARVOL DELTA

Isolation, genomic characterization and biotechnological evaluation of lactobacilli strains from chicken gastrointestinal tract. (PubMed, Microb Pathog) - "In addition, the strains exhibited strong antibacterial activity against pathogenic MRSA (Meticillin-resistant Staphylococcus aureus ATCC 67101), S. aureus ATCC 25923, Listeria monocytogenes MBG16, and VRSA (Vancomycin-resistant Staphylococcus aureus MBG89), while showing moderate activity against Salmonella Typhimurium MBG15, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13833, and Pseudomonas aeruginosa ATCC 27853. monocytogenes and S. aureus, possibly due to possible bacteriocin production. In conclusion, the strains isolated from chicken gut microbiota have a high potential to be used as probiotics in agriculture and medicine."

Journal • Gastrointestinal Disorder • Infectious Disease • Pneumonia

Structure and genome editing of type I-B CRISPR-Cas. (PubMed, Nat Commun) - "PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition, and local conformational changes of the effector complex upon R-loop formation...We further characterized the genome editing profiles of this I-B Cascade-Cas3 in human CD3+ T cells using mRNA-mediated delivery, which led to unidirectional 4.5 kb deletion in TRAC locus and achieved an editing efficiency up to 41.2%. Our study provides the structural basis for understanding target DNA recognition by type I-B Cascade and lays foundation for harnessing this system for long range genome editing in human T cells."

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Genomic and phenotypic characterization of Thermosynechococcus-like strains reveals eight species within the genus Thermosynechococcus and a novel genus Parathermosynechococcus gen. nov. (PubMed, Mol Phylogenet Evol) - "Moreover, the results also suggest the presence of two putative new genera phylogenetically alongside genus Thermosynechococcus, a thermophilic genus Parathermosynechococcus represented by PCC 6715 and a non-thermophilic genus represented by PCC 6312...Interestingly, the phylogeny of 16S-23S ITS achieved a better taxonomic relationship than that of 16S rRNA and supported the genome-based classification of Thermosynechococcus spp. Finally, the pan-genome analysis indicated a conserved pattern of genomic core among known members of Thermosynechococcus."

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Combinations of Cdc-like kinase (CLK) inhibitors with targeted oncology agents or standard chemotherapy in patient-derived multi-cell type tumor spheroids (AACR 2024) - "Among the standard chemotherapeutic drugs, doxorubicin and SN-38 demonstrated additive and greater-than-additive cytotoxicity in various spheroid types when combined with either CLK inhibitor...These agents included the XPO1 inhibitor, eltanexor, the MCL-1 inhibitor, tapotoclax, the α-isoform-specific PI3K inhibitor, inavolisib, and the pan-PI3K inhibitor, copanlisib. Notably, combinations of the CLK inhibitors with the KRAS G12D variant-specific inhibitor, MRTX-1133, showed selective activity against all tumor cell lines harboring this genetic variant. Interestingly, a strong antagonistic interaction between paclitaxel and CC-671 was observed in all thirty spheroid types, while no such interaction was observed with cirtuvivint. This project was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261201500003I."

Clinical • Melanoma • Oncology • Solid Tumor • KRAS

Salt and heat stress enhances hydrogen production in cyanobacteria. (PubMed, Photosynth Res) - "PCC6714 regarding H2 formation, increasing the PAMCOD H2 productivity from 2 nmol H2 h- 1 mol Chl a- 1 to 23 nmol H2 h- 1 mol Chl a- 1. Moreover, after the dark fermentation, the cells demonstrated proliferation in both double BG-11 and BG-11 medium enriched in NaNO3, thus showing the sustainability of the procedure."

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Poly-β-hydroxybutyrate production by Synechocystis MT_a24 in a raceway pond using urban wastewater. (PubMed, Appl Microbiol Biotechnol) - "PCC6714 MT_a24 in an outdoor bioreactor using urban wastewater as a sole nutrient source...It shows a promising approach for the cost-effective and sustainable production of biodegradable carbon-negative plastics. KEY POINTS: • High PHB production by cyanobacteria in outdoor raceway pond • Urban wastewater used as a sole source of nutrients for phototrophic growth • Potential for cost-effective and sustainable production of biodegradable plastics."

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Characterization of Poly(3-hydroxybutyrate) (P3HB) from Alternative, Scalable (Waste) Feedstocks. (PubMed, Bioengineering (Basel)) - "PCC 6714) for photoautotrophic production and the other via methanotrophic bacteria (Methylocystis sp...This research evaluates the thermal and mechanical properties, including the aging effect over 21 days, demonstrating that both P3HBs are comparable, exhibiting physical properties similar to standard P3HBs. The results highlight the promising potential of P3HBs obtained through alternative routes as biomaterials, thereby contributing to the transition toward more sustainable alternatives to fossil polymers."

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Survey of Staphylococcus aureus carriage by free-living red deer (Cervus elaphus): evidence of human and domestic animal lineages. (PubMed, Transbound Emerg Dis) - "It was followed by CC2671 (15.4%) and CC350 (6.4%)...Methicillin resistance genes mecA and mecC were not found. Our results suggest that free-living red deer may be reservoir for S. aureus in Alpine habitats."

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Cashew nut shell liquids: Antimicrobial compounds in prevention and control of the oral biofilms. (PubMed, Arch Oral Biol) - "In conclusion, both substances showed effective antibacterial and antibiofilm activity against the strains used in the study, except in viability of S. parasanguinis cells treated with t-CNSL."

Journal • Dental Disorders • Periodontitis

Genome-wide identification and characterization of Fur binding sites in the cyanobacteria synechocystis sp. PCC 6803 and PCC 6714. (PubMed, DNA Res) - "Within the isiABC operon, we identified a previously neglected gene encoding a small cysteine-rich protein, which we suggest calling, IsiE. The regulation of iron uptake, storage and utilization ultimately results from the interplay between the Fur regulon, several other transcription factors, the FtsH3 protease and the sRNA IsaR1."

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Final Destination? Pinpointing Hyella disjuncta sp. nov. PCC 6712 (Cyanobacteria) Based on Taxonomic Aspects, Multicellularity, Nitrogen Fixation and Biosynthetic Gene Clusters. (PubMed, Life (Basel)) - "This is in contrast to the formation of pseudofilaments-a main feature of the genus Hyella-which is weakly expressed in H. disjuncta PCC 6712 but prominent in Hyella patelloides LEGE 07179. Thus, our study pinpoints crucial but hidden aspects of polyphasic cyanobacterial taxonomy."

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In Situ Quantification of Polyhydroxybutyrate in Photobioreactor Cultivations of Synechocystis sp. Using an Ultrasound-Enhanced ATR-FTIR Spectroscopy Probe. (PubMed, Bioengineering (Basel)) - "Spectroscopic probes supported by ultrasound particle traps provide a powerful technology for in-line, nondestructive, and real-time process analytics in photobioreactors. This work shows the great potential of using ultrasound particle manipulation to improve spectroscopic attenuated total reflection Fourier-transformed mid-infrared (ATR-FTIR) spectra as a monitoring tool for PHB production processes in photobioreactors."

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Effect of light colour and photoperiod on biomass growth and phycocyanin production by Synechococcus PCC 6715. (PubMed, Bioresour Technol) - "PCC6715 lacks genes encoding phycoerythrins what suggests T1 type of pigmentation. Although changes in biomass pigmentation were not significant, the strain was able to adapt its photosystem what can be used in the optimization of PC production by application of different light colours."

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Dual TTK/CLK2 inhibitor, CC-671, selectively antagonizes ABCG2-mediated multidrug resistance in lung cancer cells. (PubMed, Cancer Sci) - "The computational molecule docking analysis suggests CC-671 has high binding affinity to the drug-binding site of ABCG2. In conclusion, we reveal the interaction between CC-671 and ABCG2, providing a rational of potential combinational use of CC-671 with ABCG2 substrate to overcome MDR."

Journal • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ABCG2 • MPS1

Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK2 Inhibitor for Treatment of Triple-negative Breast Cancer with a Compromised G1/S Checkpoint. (PubMed, Mol Cancer Ther) - "CC-671 was discovered using a phenotypic screen for compounds that preferentially induced apoptosis in triple-negative breast cancer cell lines while sparing luminal breast cancer cell lines...These findings are the first to demonstrate the unique inhibitory combination activity of a dual TTK/CLK2 inhibitor that preferably kills TNBC cells and shows synthetic lethality with a compromised G1/S checkpoint in breast cancer cell lines. Based on these data, CC-671 was moved forward for clinical development as a potent and selective TTK/CLK2 inhibitor in a subset of TNBC patients."

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Increased carbohydrate production from carbon dioxide in randomly mutated cells of cyanobacterial strain Synechocystis sp. PCC 6714: Bioprocess understanding and evaluation of productivities. (PubMed, Bioresour Technol) - "PCC 6714 and it can be used to boost glycogen productivity. The maximum glycogen content acquired was 2.6 g L (76.2% DCW) for mutant MT_a24 using phosphate feeding and carbon dioxide as carbon source."

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SM04690, A POTENTIAL DISEASE-MODIFYING TREATMENT FOR KNEE OSTEOARTHRITIS, FUNCTIONS THROUGH INHIBITION OF CLK2 AND DYRK1A, NOVEL MOLECULAR REGULATORS OF WNT SIGNALING, CHONDROGENESIS, AND INFLAMMATION (OARSI 2019) - "Effects on the Wnt pathway, chondrogenesis, and anti-inflammatory activity were confirmed using CLK2 specific inhibitor (CC-671) and DYRK1A specific inhibitor (Harmine), compared with DMSO. SM04690 was a potent Wnt pathway inhibitor that appeared to act via inhibition of CLK2 and DYRK1A. Pharmacological and genomic studies demonstrated, for the first time, the role of CLK2 inhibition in early chondrogenesis through effects on TCF7, and of DYRK1A inhibition in maintenance of chondrocyte function through effects on Sirt1 and FoxO1, supporting potential OA disease modification with SM04690. The specificity of effects on Wnt pathway genes highlighted the importance for chondrogenesis of modulating specific proteins (e.g., TCF7) in the Wnt pathway."