- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, cucurbitacin I (JSI-124) / H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: In vitro primary hyperparathyroidism model application of computationally repurposed drugs. (Pubmed Central) - Feb 19, 2024
Cucurbitacin I and IMD 0354 exhibited a slight inverse relationship between increased drug concentrations and cell viability, whereas DG 041 increased viability. Based on these results, further studies are needed on the mechanism of action of the repurposed drugs, including determining the effects of these drugs on cellular PTH synthesis and secretion and on the metabolic pathways that regulate PTH secretion.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Journal: Promotion of Myofibroblast Differentiation Through Repeated Treatment of Fibroblasts to Low Concentrations of PM. (Pubmed Central) - Jan 16, 2024
Treatment of fibroblasts with IMD0354, an inhibitor to nuclear factor ?B, but not with an antagonist to aryl hydrocarbon receptor, abolished the ability of PM to induce myofibroblast differentiation. These data demonstrate that potential impact of PM to fibroblast activation and fibrosis and support the importance of utilizing low concentrations and varying exposure protocols to toxicologic studies.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal, Biopsy: Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels. (Pubmed Central) - Sep 28, 2023
In contrast, proposed inhibitors of AQP water pores (acetazolamide, ginsenoside, KeenMind, TGN-020, IMD-0354) were not effective...In summary, AQP1 ion channels are important for motility in both low- and high-grade EC subtypes. Inhibition of AQP1 is a promising strategy to inhibit EC invasiveness and improve patient outcomes.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: CC16 augmentation reduces exaggerated COPD-like disease in Cc16-deficient mice. (Pubmed Central) - Mar 24, 2023
rhCC16 treatment reduced NF-kB activation in luciferase reporter A549 cells. Thus, rhCC16 treatment limits COPD progression in CS-exposed Cc16-/- mice partly by inhibiting NF-kB activation and represents a novel therapeutic approach for COPD.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Journal: Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants. (Pubmed Central) - Sep 14, 2022
IMD-0354 stimulated type I interferon antiviral response, inhibited viral entry, and down-regulated hijacked proteins. This study demonstrates that the conserved coronavirus signatures and the transcriptomic reversal approach that leverages polypharmacological effects could guide new variant therapeutic discovery.
- |||||||||| dimethylamino micheliolide (ACT001) / Tianjin Suntech Pharma
Preclinical, Journal: ACT001 suppressing M1 polarization against inflammation via NF-κB and STAT1 signaling pathways alleviates acute lung injury in mice. (Pubmed Central) - Aug 22, 2022
Our data clearly showed that ACT001-induced decrease of the M1 polarization was blocked by IMD and Flud treatment, and reversed by IKKβ and STAT1 overexpression in RAW264.7 cells. In conclusion, we discovered that ACT001 significantly alleviates inflammation and limits M1 phenotype of pulmonary macrophages via suppressing NF-κB and STAT1 signaling pathways, providing new insights for the development of drugs to treat ALI/ARDS.
- |||||||||| Journal: Integrative Analysis for Identification of Therapeutic Targets and Prognostic Signatures in Non-Small Cell Lung Cancer. (Pubmed Central) - Apr 19, 2022
On the contrary, high mRNA expressions of CBL, FYN, LRKK2, and SOCS2 were associated with a significantly better prognosis. Furthermore, our drug target analysis for these hub genes suggests a potential use of Trichostatin A, Pracinostat, TGX-221, PHA-793887, AG-879, and IMD0354 antineoplastic agents to reverse the expression of these DEGs in NSCLC patients.
- |||||||||| enzalutamide capsule / Generic mfg., abiraterone acetate / Generic mfg.
Journal, IO biomarker: Emergence of Enzalutamide resistance in prostate cancer is associated with BCL-2 and IKKB dependencies. (Pubmed Central) - Mar 15, 2022
Inhibition of MIF alleviated LPS-induced inflammation in HEI-OC1 cells via inactivating the NF-κB signaling, which might provide a better understanding for SSNHL development. Our findings identify BCL-2 and IKKB dependencies in clinically relevant ENZ-resistant prostate cancer cells in vitro and in vivo but indicate that IKKB upregulation appears to have greater relevance to the progression of human castrate resistant prostate cancer.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: Lidocaine relieves murine allergic rhinitis by regulating the NF-κB and p38 MAPK pathways. (Pubmed Central) - Feb 8, 2022
The results indicated that these two compounds exhibited similar inhibitory effects on AR mice as those noted with the use of lidocaine. These findings suggested that lidocaine represented a novel therapeutic agent for AR.
- |||||||||| colistin sulphate / Generic mfg.
Benzimidazole Isosteres of Salicylanilides are Highly Active Colistin Adjuvants (In-Person Room (Virtual Room)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_3375;
Herein, we report the activity of a second-generation library of IMD-0354 analogues incorporating a benzimidazole moiety as an amide isostere. We identified several analogues that show increased colistin potentiation activity against the Gram-negative bacteria: Klebsiella pneumoniae and Acinetobacter baumannii.
- |||||||||| colistin sulphate / Generic mfg.
Clinical, Journal: Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants. (Pubmed Central) - Dec 18, 2021
Herein, we report the activity of a second-generation library of IMD-0354 analogues incorporating a benzimidazole moiety as an amide isostere. We identified several analogues that show increased colistin potentiation activity against Gram-negative bacteria.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Journal: Cardiomyocytes' prolonged IL-2 incubation induces enhancement in L-type Ca channels mediated by IKK/NF-κB signalling. (Pubmed Central) - Jul 29, 2021
The cardiomyocytes incubated in a Kraftbrühe solution containing IL-2 plus PDTC as a specific inhibitor of inducible nitric oxide synthase (iNOS) for 2 hours had a similar I increase compared to the cells incubated only in IL-2. IL-2-induced enhancement in L-type Ca channels was mediated by IKK/NF-κB signalling, but not via iNOS mRNA signalling.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: Development and characterisation of a novel, megakaryocyte NF-κB reporter cell line for investigating inflammatory responses. (Pubmed Central) - May 15, 2021
Notably, Meg-01R cells were able to respond to LPS (non-ultrapure) although it was not able to react to ultrapure LPS due to the lack of sufficient TLR4 molecules on their surface. For the first time, we report the development and characterisation of a novel megakaryocyte NF-κB reporter cell line (Meg-01R) as a robust tool to study the inflammatory responses/signalling of megakaryocytes upon stimulation with a broad range of inflammatory molecules that can affect NF-κB activity.
- |||||||||| Journal: Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria. (Pubmed Central) - Apr 7, 2021
Enhanced mortality was independent of direct effects of IKK16 on P. entomophila growth in vitro but was associated with higher bacterial loads in vivo (i.e., reduced resistance). Together, these results provide new insight into the regulation of the bed bug immune system and suggest that administration of entomopathogens in combination with inhibition of immune signaling pathways to reduce infection resistance may be effective for biological control of bed bugs.
- |||||||||| TriptoSar (triptolide) / Pierre Fabre, IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Journal: MiR-200b suppresses TNF-α-induced AMTN production in human gingival epithelial cells. (Pubmed Central) - Mar 17, 2021
Furthermore, both inhibitors reduced AMTN mRNA levels in the presence or absence of TNF-α. These results suggest that miR-200b suppresses AMTN expression by targeting to AMTN and IKKβ mRNAs in the human gingival epithelial cells.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Clinical, Journal: Structure Function Studies on IMD 0354 Identifies Highly Active Colistin Adjuvants. (Pubmed Central) - Jan 23, 2021
We recently disclosed that the known IKK-β inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-negative strains. In this report, we explore the structure-activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae .
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: Attenuation of experimental autoimmune uveoretinitis in mice by IKKβ inhibitor IMD-0354. (Pubmed Central) - Nov 6, 2020
Furthermore, IMD-0354 treatment significantly inhibited the levels of several Th1/Th17-mediated pro-inflammatory cytokines in vitro. Our current data demonstrate that inhibition of IKKβ with IMD-0354 ameliorates inflammatory responses in the mouse EAU model, suggesting that IMD-0354 may be a promising therapeutic agent for human endogenous uveitis.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design
Journal: New Antimicrobial Bioactivity against Multidrug-Resistant Gram-Positive Bacteria of Kinase Inhibitor IMD0354. (Pubmed Central) - Oct 8, 2020
Lastly, we found that IMD0354 is able to inhibit vancomycin-resistant Staphylococcus aureus (VRSA) initial cell attachment and biofilm formation at sub-MIC levels and above. Our work highlights that the NF-κB inhibitor IMD0354 has promising potential as a lead compound and an antimicrobial therapeutic candidate capable of combating multidrug-resistant bacteria.
- |||||||||| IMD 0354 / Institute of Medicinal Molecular Design, IMD-0354 / Institute of Medicinal Molecular Design, Verzenio (abemaciclib) / Eli Lilly
Journal, Combination therapy: Charge and Size Dual Switchable Nanocage for Novel Triple-Interlocked Combination Therapy Pattern. (Pubmed Central) - Oct 3, 2020
Furthermore, PA/PI-ND has improved anti-tumor efficiency resulting from the third synergistic effect provided by chemoimmunotherapy. Taken together, PA/PI-ND is a promising strategy to guide the design of future drug delivery carriers and cancer combination therapy.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design, mycophenolate sodium / Generic mfg.
Journal: Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2. (Pubmed Central) - Sep 25, 2020
Although MPA reduced the viral RNA level by only ~100-fold, its EC was as low as 0.87µM, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets coronaviral papain-like protease and its study would be useful in the development of novel anti-SARS-CoV-2 drugs.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design, AR-12 / Arno Therap
Clinical, Journal: Repurposing Eukaryotic Kinase Inhibitors as Colistin Adjuvants in Gram-negative Bacteria. (Pubmed Central) - Jul 7, 2020
We report IMD-0354, an inhibitor of IKK-β, as a markedly effective adjuvant in colistin-resistant bacteria, and also describe AR-12 (OSU-03012), an inhibitor of PDK-1, as a potentiator in colistin-sensitive strains. This report comprises the first description of the novel cross-reactivity of these molecules.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: IKKβ Inhibitor IMD-0354 Attenuates Radiation Damage in Whole-body X-Irradiated Mice. (Pubmed Central) - Jun 28, 2020
IMD-0354 administration significantly suppressed the lethality induced by whole-body X-irradiation, and the survival rate increased by 83%. The NF-κB p65 and IκBα in bone marrow and spleen cells were significantly lower in IMD-0354-treated mice than in irradiated mice, suggesting that the IKKβ inhibitor IMD-0354 exerts a radiomitigative effect by suppressing the NF-κB.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Journal: Role of NF-κB in cytochrome P450 epoxygenases down-regulation during an inflammatory process in astrocytes. (Pubmed Central) - May 13, 2020
Therefore, in order to explore the effects of inflammation and NF-κB activation in CYP2J3 and CYP2C11 regulation, rat primary astrocytes cultures were treated with LPS with and without IMD-0354 (selective NF-κB inhibitor)...Results shown that LPS treatment is able to down-regulate astrocyte CYP2J3 and CYP2C11 mRNA, protein and activity. Additionally, we have identified NK-κB as the transcription factor involved in this regulation.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design, Nexavar (sorafenib) / Bayer, Amgen
Journal: Selective targeting of tumor cells and tumor associated macrophages separately by twin-like core-shell nanoparticles for enhanced tumor-localized chemoimmunotherapy. (Pubmed Central) - Dec 28, 2019
The combination of TAM-based immunotherapy with sorafenib (SF) could be conceivably quite more effective in hepatocellular carcinoma (HCC) treatment...In this study, twin-like core-shell nanoparticles (TCN) were developed for synchronous biodistribution and separated cell targeting delivery of SF and TAM re-polarization agents IMD-0354 to cancer cells and TAM to enhance tumor-localized chemoimmunotherapy, respectively...What's more, the results of antitumor efficiency in vivo and phenotype analysis of TAM in tumor tissues proved that CMCS/SF-CLN and CMCS/M-IMD-CLN exhibited superior synergistic antitumor efficacy and M2-type TAM polarization ability compared with SF treatment in Hepa1-6 tumor bearing mice. Consequently, TCN which was the combination of co-administration and nano-drug delivery systems has great potential to be used in tumor-localized chemoimmunotherapy in clinics.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Journal: Ceria nanoparticles promoted the cytotoxic activity of CD8 T cells by activating NF-κB signaling. (Pubmed Central) - Dec 23, 2019
Importantly, while the P14 cells were simultaneously treated by IMD-0354, a specific inhibitor of NF-κB signaling, the increases of IL-2 and TNF-α productions and granzyme B and perforin releases were remedied, and the P14 cells eventually exhibited the natural killing activity in vitro. Thus, our results demonstrated that CNP treatment promoted the cytotoxic activity of CTL cells and provide new ideas in the usage of CNPs and fascinating pharmacological potentials for clinical application, especially cancer immunotherapy.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Inhibition of glutamine uptake by small molecular SLC1A5 inhibitor IMD-0354 inhibits melanoma () - Nov 21, 2019 - Abstract #SMR2019SMR_309;
In addition to glutamine uptake inhibition, IMD0354 attenuated fatty acid synthesis, via its inhibition of its ratelimiting enzyme, Acetyl-CoA carboxylase. The combined inhibition of glutamine uptake and fatty acid synthesis by IMD-0354 support its further development for preclinical assessment.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Journal: Selective IKK2 inhibitor IMD0354 disrupts NF-κB signaling to suppress corneal inflammation and angiogenesis. (Pubmed Central) - Oct 27, 2019
In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-α expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-κB by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-κB signaling in the development of pathologic corneal neovascularization.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: A novel IkB kinase inhibitor attenuates ligature-induced periodontal disease in mice. (Pubmed Central) - Jul 13, 2019
Further, it is believed the FA-Dex-LA can potentially applied in cancer treatment. IMD-0354 regulated bone resorption by ligature-induced periodontitis, and it is suggested that the inhibition of IKK via down-regulation of NF kappa-B may provide periodontal patients with an effective approach to prevent or suppress the disease.
- |||||||||| IMD-0354 / Institute of Medicinal Molecular Design
Preclinical, Journal: Central IKK2 inhibition ameliorates air pollution mediated hepatic glucose and lipid metabolism dysfunction in mice with type II diabetes. (Pubmed Central) - May 29, 2019
...KKAy mice, a genetically susceptible model of type II diabetes mellitus, were administered intra-cerebroventricularly with IKK2 inhibitor (IMD-0354) and were exposed to either concentrated PM2.5 or filtered air (FA) for 4 weeks simultaneously via a versatile aerosol concentration exposure system...Although the treatment did not affect hepatic inflammation or endoplasmic reticulum stress, it inhibited the expression of the enzymes for gluconeogenesis and lipogenesis in the liver. Therefore, our current finding indicates an important role of hypothalamic inflammation in PM2.5 exposure-mediated hepatic glucose and lipid metabolism disorder.
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