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Immune System Diseases

Hemic and Lymphatic Diseases

Respiratory Diseases

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Disease Domain	Count

Neoplasms	1
Immune System Diseases	1
Hemic and Lymphatic Diseases	1

Top 5 Drug Type	Count

Small molecule drug	1

Top 5 Target	Count

CALR x CD38 x CD47 x DHODH	1

AbstractSalt marshes of the northern Gulf of Mexico provide many ecosystem services, including supporting some of the USA’s most productive fisheries. Early work identified links between salt marsh area and commercial shrimp landings, while more recent research highlighted the importance of marsh edge. Many species appear to be restricted to the outer few meters of the vegetated marsh even when large areas are flooded for extended periods. We hypothesized that low dissolved oxygen (DO), driven by high respiration rates, may limit more extensive use of flooded marsh. To evaluate this, we continuously logged DO 5 cm above the substrate along transects at 10, 5, and 1 m into open water adjacent to the marsh edge and at 1, 5, and 10 m into the flooded marsh, for 48+ h periods at 10 sites in Mississippi Sound, AL, during the summer of 2024. DO levels 10 and 5 m into the flooded marsh regularly dropped to stressful levels (< 4 mg/L), often becoming hypoxic (< 2 mg/L) for periods of several hours. In addition to predictable diurnal DO cycles, we identified precipitous drops in DO on the flooded marsh surface around midday at some sites, coinciding with the beginning of the ebb tide. This suggests that even during bright sunny conditions, respiration can exceed aquatic photosynthesis in the shallow flooded marsh. Our findings suggest that much of the flooded marsh may be physiologically stressful for many aquatic species. Increasing temperatures and nutrient loads in our coastal waters will further exacerbate poor DO conditions and may degrade the suitability of this essential fish habitat.

21 Apr 2025·Cancer Research

Abstract 6902: Promising therapeutic effects of pyrimidine synthesis inhibition by a novel dihydroorotate dehydrogenase inhibitor in small cell lung cancer

Author: Hertlein, Erin ; Coss, Christopher C. ; Bennett, Chad E. ; Vibhute, Sandip ; Elgamal, Ola A. ; Nourmohammadi, Bahareh ; Amann, Joseph M. ; Byrd, John C. ; Goodwin, Thomas E. ; Carbone, David P.

AbstractSmall-cell lung cancer is an aggressive subtype of lung cancer with poor prognosis and poor overall survival and comprises approximately 15% of all lung cancers. SCLC, unlike NSCLC, has no known targetable driver mutations and, therefore, targeted therapeutics have been lacking. The frontline therapy for SCLC is platinum-etoposide chemotherapy, a regimen that has been in use for 30 years. Although patients respond well to this combination initially, they almost always relapse shortly after the start of therapy and second line therapies typically provide only a few months of benefit. Clearly, better therapeutics are necessary for the treatment of SCLC. Cancer cells often have dysregulated metabolic pathways. These changes are often necessary to enable the continued proliferation of the cancer cells. Therefore, key metabolic enzymes can have a crucial role in tumor cells survival and can be considered targets for cancer treatment. According to some recent studies, dihydroorotate dehydrogenase (DHODH), which catalyzes the conversion of dihydroorotate to orotate in the pyrimidine de novo synthesis pathway, has a particular role in the survival of different types of cancers including leukemia and SCLC. We evaluated the effect of HOSU-53, a novel DHODH inhibitor, on SCLC tumor growth in vitro and in vivo. We measured IC50s of 18 SCLC cell lines in vitro using CellTiter-Glo® Luminescent Cell Viability Assay and most SCLC cells showed sensitivity to HOSU-53 treatment in the low nanomolar range. Additionally, to determine the role of salvage pathway in HOSU-53 sensitivity, we treated the sensitive and resistant cells in parallel with HOSU-53 alone or in combination with exogenous uridine. In the presence of uridine, cell viability was significantly rescued in resistant cells compared to HOSU-53 treatment as single agent. However, we did not observe rescued cell viability in sensitive SCLC cells. These results suggesting that in SCLC cells which are resistant to de novo pyrimidine inhibition, activation of salvage pathway may be one of the compensatory mechanisms for tumor cells to sustain their survival. To evaluate the effect of DHODH inhibition on SCLC tumor growth in vivo, we treated xenograft mice models with HOSU-53 alone or in combination with etoposide plus cisplatin as the standard chemotherapy for SCLC. We observed a significant decrease of tumor volume when HOSU-53 was used alone and in combination, without significant animal weight loss. Together, these data demonstrated the promising efficacy of HOSU-53 in different SCLC subtypes and support the strategy of targeting DHODH as a potential therapy to treat SCLC. These findings support the initiation of a phase l clinical trial to evaluate the preliminary efficacy and tolerability of HOSU-53; therefore, we have initiated a first-in-human phase I trial of this agent.Citation Format:Bahareh Nourmohammadi, Ola A. Elgamal, Sandip Vibhute, Christopher C. Coss, Thomas E. Goodwin, Erin Hertlein, Joseph M. Amann, Chad E. Bennett, John C. Byrd, David P. Carbone. Promising therapeutic effects of pyrimidine synthesis inhibition by a novel dihydroorotate dehydrogenase inhibitor in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6902.

01 Apr 2025·Seminars in Ultrasound, CT and MRI

Imaging of Shoulder Labral Injuries in Athletes: A Comprehensive Review

Review

Author: Barfoot, Garrett ; Bajaj, Mahek ; Singh, Shiva ; Bajaj, Suryansh ; Kumar, Shruti ; Bajaj, Gitanjali ; Vattoth, Aysha Lamis

100 Deals associated with Hendrix College

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100 Translational Medicine associated with Hendrix College

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Pipeline

Pipeline Snapshot as of 09 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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1

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