P1, N=1, Terminated, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Completed --> Terminated; Drug company discontinuing study.

P1, N=1, Completed, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Recruiting --> Completed | N=60 --> 1 | Trial completion date: Oct 2028 --> Jan 2025 | Trial primary completion date: Dec 2027 --> Jan 2025

P1, N=12, Active, not recruiting, Northwestern University | Completed --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2028

The most common grade ≥3 treatment-emergent adverse events were asymptomatic amylase elevation (23.1%), anemia (20.0%), and asymptomatic lipase elevation (18.5%). These data suggest clinical activity and acceptable tolerability for cerdulatinib in patients with relapsed/refractory PTCL.

P1, N=25, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Enrolling by invitation --> Recruiting

P1, N=12, Completed, Northwestern University | Active, not recruiting --> Completed | Trial completion date: Aug 2022 --> Dec 2024

P=N/A, N=149, Recruiting, Kissei Pharmaceutical Co., Ltd.

P1, N=36, Recruiting, University of California, San Diego | Not yet recruiting --> Recruiting

P1/2, N=240, Recruiting, Aptose Biosciences Inc. | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: May 2026 --> Nov 2026

P1, N=60, Recruiting, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Not yet recruiting --> Recruiting

Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3 mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax or 5-azacytidine...Cells selected for stable acquired resistance to TUS exhibited increased BAX and hypersensitivity to venetoclax (1900-fold), navitoclax and MCL1 inhibitors. MV-4-11 FLT3-ITD clones expressing NRASG12D revealed that high-level expression of NRASG12D generated modest resistance to TUS and greater resistance to venetoclax (VEN), yet the TUS/VEN combination exhibited synergy in NRASG12D AML model. Favorable preclinical safety and pharmacology properties, the efficacy of the TUS/VEN combination in a murine model, and the synthetic lethal vulnerability to VEN that accompanies TUS resistance provide the basis for exploration of the TUS/VEN combination in patients with relapsed or refractory AML.

Currently there are five selective SMIs available in the United States with demonstrated efficacy for HS in clinical studies including apremilast, topical ruxolitinib, upadacitinib, fostamatinib, and sirolimus. These selective SMIs target four pathways hypothesized to be important to HS pathogenesis including phosphodiestase 4, Janus kinases, spleen tyrosine kinase, and mammalian target of rapamycin. Several new SMIs are currently in the clinical trial pipeline targeting Bruton's tyrosine kinase, aryl hydrocarbon receptors, heat shock protein 90 as well as interleukin-1 and -17 signaling pathways.

P1/2, N=8, Active, not recruiting, Imperial College London | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Oct 2025

These findings not only pinpoint the oncogenic metabolite cholesterol as a hidden culprit in AB-HCC subtype, but also enlighten a novel combination strategy to rejuvenate tumor metabolism.

Overall, by integrating network and structural pharmacology with molecular modeling, we determined two complementary strategies with the potential to annihilate the AML network, one in the form of repurposable drug combinations and the other as a de novo synthesized triple-targeting agent. These target-drug interactions could be prioritized for preclinical and clinical testing toward precision medicine for AML.

Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.

P1, N=35, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed

P1, N=25, Enrolling by invitation, National Heart, Lung, and Blood Institute (NHLBI) | Not yet recruiting --> Enrolling by invitation

P1, N=36, Not yet recruiting, University of California, San Diego

Exploration of the IMPATT database led to the discovery of a lead compound similar to Fostamatinib, currently used for AurKB. Initial molecular docking and MMGBSA-based binding energy analysis were followed by molecular dynamics simulation (MDS) and free energy landscape (FEL) analysis to validate the ligand's binding efficacy and understand dynamic processes within the biological system. The identified potential biomarkers and lead molecule provide novel insights into the correlation between blood cell transcripts and ALS pathology, paving the way for blood-based diagnostic tools for early ALS detection and ongoing disease monitoring.

P2, N=40, Terminated, Iacta Pharmaceuticals | In an over abundance of caution the study was terminated. All adverse events resolved with no sequelae.

Moreover, Spleen Tyrosine Kinase (SYK) inhibition with R406, the active metabolite of the drug Fostamatinib, previously demonstrated to suppress NETs in primary neutrophils, effectively reduced NETs release in dHL-60 cells. dHL-60 cells, offering easier manipulation, consistent availability, and no donor variability in functional responses, possess characteristics suitable for high-throughput studies evaluating NETosis. Overall, dHL-60 cells may be a valuable in vitro model for deciphering the molecular mechanisms of NETosis in response to LPS, contributing to our available tools for understanding this complex immune process.

Human neuroblastoma M1C cells harboring wild-type tau (4R0N) were used with the tetracycline off (TetOff) induction system. In this model of neuronal tauopathy, the effects of the Syk inhibitors-BAY 61-3606 and R406-on tau phosphorylation and oligomerization were explored using several phosphorylated tau-specific antibodies and an oligomeric tau antibody, and the effects of these Syk inhibitors on autophagy were examined using western blot analyses...In vivo, the Syk inhibitor R406 decreased phosphorylated tau levels in wild-type mice. These findings suggest that Syk inhibitors offer novel therapeutic strategies for tauopathies, including AD.

P1/2, N=260, Recruiting, Aptose Biosciences Inc. | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Feb 2024 --> May 2026

Transforming growth factor-β receptor kinase inhibitor (TRKI), Src family kinase inhibitor (PP2) and Syk inhibitor (R406) were used to identify the molecules influencing these interactions...In vivo analyses revealed that PLT-enhanced peritoneal dissemination was suppressed by PP2. Overall, the present study revealed the important role of the Srk family in the interactions between PLTs and GC cells, suggesting kinase inhibitors as promising therapeutic agents to mitigate the progression of peritoneal metastasis in patients with GC.

P1, N=20, Not yet recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial primary completion date: Aug 2024 --> Aug 2025

P2, N=40, Not yet recruiting, Inova Health Care Services

P2, N=156, Not yet recruiting, CSPC Ouyi Pharmaceutical Co., Ltd.

P1, N=11, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Aug 2024 | Trial primary completion date: Apr 2025 --> Aug 2024

Together, this study offers preclinical evidence supporting dual inhibition of SYK and EGFR as a promising treatment for chemoresistant ovarian cancer that disrupts DNA synthesis by impairing formation of the prereplication complex. These findings warrant further clinical investigation to explore the potential of this combination therapy in overcoming drug resistance and improving patient outcomes.

P2, N=163, Completed, Oscotec Inc. | Unknown status --> Completed

Fostamatinib has been studied for its possible use in the treatment of hepatocellular cancer because it is a more convenient therapy choice for patients and has minor side effects on the human body...Additionally, it completely fulfills the criteria of drug-likeliness rules. Thus, FOR proves to be an efficient drug candidate for future in-vivo studies against hepatocellular carcinoma.

P2, N=144, Recruiting, CSPC Ouyi Pharmaceutical Co., Ltd.

P1, N=134, Completed, Hutchison Medipharma Limited | Unknown status --> Completed | N=217 --> 134

P2/3, N=110, Recruiting, Hutchison Medipharma Limited | Active, not recruiting --> Recruiting

P1, N=45, Completed, Hutchison Medipharma Limited | Unknown status --> Completed

P1, N=6, Completed, Hutchmed | Active, not recruiting --> Completed | N=10 --> 6

P3, N=272, Active, not recruiting, Hutchison Medipharma Limited | N=188 --> 272 | Trial completion date: Dec 2023 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Oct 2024

The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors.

Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy.

P1, N=11, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 11

P1, N=30, Not yet recruiting, Stefanie Sarantopoulos, MD, PhD. | Initiation date: Jun 2024 --> Sep 2024