AC001 / Allied Health, University of Haifa - LARVOL DELTA

Duddingtonia flagrans and its crude proteolytic extract: concomitant action in sheep coprocultures. (PubMed, Vet Res Commun) - "The treatments with active proteolytic crude extract (G2) and active proteolytic crude extract + AC001 conidia (G3) were significantly different (p < 0.01) from the control group with denatured proteolytic crude extract (G1). AC001 and its proteolytic crude extract acted concomitantly on helminths directly in the fecal environment, suggesting potential future applications in the field."

Journal • Gastrointestinal Disorder • Infectious Disease

Gain and loss‐of‐function screens identify targets with improved AAV production (ESGCT 2023) - "Engineering of clonal suspension-adapted HEK293 cells: A proprietary clonal suspension-adapted HEK293 cell line (AC001.230) was developed that shows improved productivity for 7 out of 10 tested serotypes compared to 293F cells...Two independent suspension-adapted knockout cell lines (AC003 and AC010) were developed that show greater than 2-fold improvement in AAV9 production capacity. The findings from these approaches have the potential to significantly reduce the cost of rAAV gene therapy, making it more widely accessible to patients."

Gene Therapies

Efficacy evaluation of a commercial formulation with Duddingtonia flagrans in equine gastrointestinal nematodes. (PubMed, J Equine Vet Sci) - "In this context, this study aimed to evaluate the in vitro efficacy of the commercial formulation Bioverm, composed of the fungus Duddingtonia flagrans strain AC001, in the reduction of gastrointestinal nematode larvae in equine feces...in tests. The recommended dose of 0.4 grams, containing 10 chlamydospores per gram of product, reduced larvae by 44.23%, while the extrapolated dose of 1.0 grams with the same concentrations of chlamydospores (10/g) resulted in a reduction of 57.20%, indicating the effectiveness of the product in controlling infective larvae."

Journal • Gastrointestinal Disorder

Compatibility study of Duddingtonia flagrans conidia and its crude proteolytic extract. (PubMed, Vet Parasitol) - "This study aimed to evaluate the concomitant use of the nematophagous fungus Duddingtonia flagrans (AC001) and its protease-rich crude extract for the in vitro control of Panagrellus sp., Haemonchus spp., and Trichostrongylus spp...In turn, there was a difference (p < 0.01) between (G5) and (G2). The results this study indicate a positive effect from the compatible use of the D. flagrans fungus and its enzymatic crude extract (protease), which has been demonstrated here for the first time and with potential field applications for further designs."

Journal • Gastrointestinal Disorder

A High-Throughput Small Molecule Screen Identifies Targets That Increase AAV9 Production in Suspension HEK293 Cells (ASGCT 2023) - "The top 70 performing compounds were re-evaluated in a dose-response manner on our proprietary HEK293 cell line (AC001.230)...We have confirmed these findings using capsid titer and vector genome quantification using two reporter constructs. Evaluation of SM-016 is ongoing to apply these findings for production of FDA-approved therapeutic transgenes with multiple AAV serotypes and in a large-scale bioreactor system."

Gene Therapies

Targeted CRISPR/Cas9 Screen Identifies Superior HEK293 Cell Lines for AAV9 Production (ASGCT 2023) - "To address this, we used clonal isolation and high-throughput screening to develop a proprietary clonal suspension-adapted HEK293 cell line (AC001.230) that produces AAV9 with increased potency compared to HEK 293F cells...We have confirmed these findings using capsid titer and vector genome quantification using a reporter construct. Studies are underway to evaluate the potency of these cell lines for production of FDA-approved therapeutic transgenes using multiple AAV serotypes and in a large-scale bioreactor system."

Preclinical • Infectious Disease

Association between Duddingtonia flagrans, dimethylsulfoxide and ivermectin for the control of Rhabditis spp. in cattle. (PubMed, Trop Anim Health Prod) - "The objective was to evaluate the combined use of Duddingtonia flagrans (AC001), 10% dimethylsulfoxide (DMSO), and 1.9% ivermectin for the in vivo control of Rhabditis spp., in naturally infected Gyr cattle...It was concluded that the combination of chemical compounds and D. flagrans in a single application was effective for the in vivo control of Rhabditis spp. in naturally infected cattle."

Journal • Infectious Disease • Otorhinolaryngology

"Also thanks to my external #mentors, #coaches and sponsors including @roberthiggins32 @JFreischlag @DouglasEWood1 @ACC001 @TomVargheseJr @cllaucll2y @carriesims20 and countless others 6/" (@DavidCookeMD)

Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling. (PubMed, Theranostics) - "ACT001 exhibits antitumor activity either as a single agent or in combination with SHP099, which provides significant survival benefits for GSC tumor xenograft-bearing animals. Our data demonstrate AEBP1 as a new druggable target in GBM and ACT001 as a potential therapeutic option for improving the clinical treatment of GBM in combination with SHP099."

Journal • Glioblastoma • Glioma • Oncology • Solid Tumor • AEBP1

Computational-aided design: minimal peptide sequence to block dengue virus transmission into cells. (PubMed, J Biomol Struct Dyn) - "One of the peptides, AC 001, was able to reduce about 40% of DV plaque formation...This work identifies the minimal peptide sequence required to inhibit DV replication and explains the behavior observed on an atomic level using computational study. Communicated by Ramaswamy H. Sarma."

Journal • Dengue Fever

"Registration link on tweet below! #whyumichCTsurgery #whyumichsurgery @UMichSCRUBS @UMichMedAdmiss @UMichSurgery @ThoracicStudent @GAilawadiMD @ACC001 @jdimick1 @DLikosky @MikeTPhD @CBATS1 @UMichCHOPFellow" (@UMichCTSurgery)

"Ping @GAilawadiMD @ACC001 @KarenMKimMD1 @ShinFukuharaMD @BoYangMD @UMichSurgery @umichCVC @kiranlagisetty @ewakeam @JulesLin99 @DLikosky @MikeTPhD @jdimick1 @DavidCookeMD @TomVargheseJr @UMichCHOPFellow @UM_IHPI @UMichMedAdmiss @SocietyofBAS @AraVaporciyan @UMichCardiology" (@UMichCTSurgery)

Cardiovascular

ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma. (PubMed, Cell Death Dis) - "Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway."

Combination therapy • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Anticancer Effects of ACT001 via NF-κB Suppression in Murine Triple-Negative Breast Cancer Cell Line 4T1. (PubMed, Cancer Manag Res) - "ACT001 is a novel sesquiterpene lactone derivative with anticancer effects, including the reversal of tamoxifen resistance in estrogen receptor-positive breast cancer cells. Our results suggest that ACT001 exerts its anticancer effects by inducing apoptosis in murine TNBC cell line 4T1 and regulates the tumor microenvironment by attenuating angiogenesis and accumulation of MDSCs in 4T1 tumors. The underlying mechanism may involve the suppression of NF-κB activity."

Journal • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CSF2 • ER

ACT001 reduces the expression of PD-L1 by inhibiting the phosphorylation of STAT3 in glioblastoma. (PubMed, Theranostics) - "ACT001 inhibits PD-L1 transcription and modulates anti-tumor immune response in glioma bearing mice. These findings will help us to understand the mechanism of ACT001 in GBM therapy."

IO Biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD 163 • STAT3

Map-based cloning of genes encoding key enzymes for pigment synthesis in Auricularia cornea. (PubMed, Fungal Biol) - "In this study, the white strain ACW001 and the purple strain ACP004 of A. cornea were used as dikaryotic parents...We discuss the deficiencies and advantages of map-based cloning in fungi vs. plants, and summarize the steps and requirements of the map-based cloning method for fungi. This study has provided novel ideas and methods for locating functional genes in fungi."

Journal • Ophthalmology

"Ping @JessicaLuc1 @womeninsurgery @abribriesco43 @DavidCookeMD @ACC001 @ctsnetorg @UVA_TCV_Surgery @Hirji1987 @JasonHanMD @JordanBloomMD @CoyanGarrett @abmozer @claudenlouis @BrighamWomens @ABTS17 @EACTS @URMCSurgery @StanfordCTSurg @MarylandSurg @ColumbiaSurgery @WashUSurgery" (@TSRA_official)

Clinical

Combined use of ivermectin, dimethyl sulfoxide, mineral oil and nematophagous fungi to control Rhabditis spp. (PubMed, Vet Parasitol) - "The objective of this study was to assess the combined use of ivermectin 1%, dimethyl sulfoxide 1% and mineral oil 100% containing nematophagous fungi of both Duddingtonia flagrans (AC001) and Monacrosporium thaumasium (NF34) species to control in vitro Rhabditis spp...The results demonstrated that all experimentally treated groups differed statistically (p < 0.01) from the control group. In the present study, the use of dimethyl sulfoxide 1% and mineral oil 100% in conjunction with conidia fungi portrayed noteworthy outcomes, which represents a future premise for the combined use of nematophagous fungi within these vehicles in both controlling Rhabditis spp."

Journal

"We might be interested in this Bin! Can you send some details? @ACC001" (@ewakeam)

An Extended-Spectrum Beta-Lactamase-Producing Hybrid Shiga-Toxigenic and Enterotoxigenic Escherichia coli Strain Isolated from a Piglet with Diarrheal Disease in Northeast China. (PubMed, Foodborne Pathog Dis) - "Phylogenetic analysis showed that STEC/ETEC S17-13, STEC S17-20, avian pathogenic E. coli (APEC) O78, and APEC ACN001 are located in the same evolutionary branch, indicating that they may originate from a common ancestor...The emergence of novel hybrid E. coli strains presents a new public health risk. More attention must be paid to these hybrid pathogens during typing and epidemiological surveillance of E. coli infections, which challenges the traditional diagnostics of E. coli infections."

Journal

Efficiency of the Bioverm (Duddingtonia flagrans) fungal formulation to control in vivo and in vitro of Haemonchus contortus and Strongyloides papillosus in sheep. (PubMed, 3 Biotech) - "flagrans-AC001) was efficient in reducing the population of H. contortus and S. papillosus under laboratory conditions in sheep feces. However, further studies are needed under natural conditions of ruminant grazing to prove the efficiency of this product."

Journal • Preclinical

Anti-neuroinflammatory effects of dimethylaminomylide (DMAMCL, i.e., ACT001) are associated with attenuating the NLRP3 inflammasome in MPTP-induced Parkinson disease in mice. (PubMed, Behav Brain Res) - "Moreover, it attenuates microglial activation in the nigrostriatal pathway. Overall, our study showed that ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by MPTP."

Journal • Preclinical

"And thank you to the @UMichCTSurgery community for their robust support!! @DLikosky @MikeTPhD @BoYangMD @ACC001 @kiranlagisetty @K_Kleeman @JulesLin99 @curtisbars" (@AlexBresciaMD)

ACT001 modulates the NF-κB/MnSOD/ROS axis by targeting IKKβ to inhibit glioblastoma cell growth. (PubMed, J Mol Med (Berl)) - "The inhibition of p-IKKβ induced the generation of ROS. ACT001 promoted the generation of ROS by regulating MnSOD expression to induce G/M phase arrest."

Journal • BAX • CCNB1 • CDK1