^
7d
Preclinical development of tuspetinib for the treatment of acute myeloid leukemia. (PubMed, Cancer Res Commun)
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.
Preclinical • Journal
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FLT3 (Fms-related tyrosine kinase 3) • SYK (Spleen tyrosine kinase) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • RPS6KA3 (Ribosomal Protein S6 Kinase A3)
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FLT3 mutation • MCL1 expression • NRAS G12
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Venclexta (venetoclax) • azacitidine • navitoclax (ABT 263) • tuspetinib (HM43239)
15d
Selective small molecule inhibitors for hidradenitis suppurativa: Today and tomorrow. (PubMed, J Am Acad Dermatol)
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.
Review • Journal
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mTOR (Mechanistic target of rapamycin kinase) • BTK (Bruton Tyrosine Kinase) • TNFA (Tumor Necrosis Factor-Alpha) • SYK (Spleen tyrosine kinase) • IL17A (Interleukin 17A)
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Tavalisse (fostamatinib)
24d
FOSTAMR: Fostamatinib in the Treatment of Chronic Active Antibody Mediated Rejection (clinicaltrials.gov)
P1/2, N=8, Active, not recruiting, Imperial College London | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Oct 2025
Enrollment closed • Trial completion date
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Tavalisse (fostamatinib)
1m
Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis. (PubMed, J Adv Res)
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.
Journal
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IGF2 (Insulin-like growth factor 2) • RAD21 (RAD21 Cohesin Complex Component)
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Tavalisse (fostamatinib)
1m
Computer-Aided Identification and Design of Ligands for Multi-Targeting Inhibition of a Molecular Acute Myeloid Leukemia Network. (PubMed, Cancers (Basel))
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.
Journal
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DNMT3A (DNA methyltransferase 1)
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Iclusig (ponatinib) • Erivedge (vismodegib) • Tavalisse (fostamatinib)
2ms
Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction. (PubMed, Anticancer Res)
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.
Journal
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PARP1 (Poly(ADP-Ribose) Polymerase 1) • CASP3 (Caspase 3)
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Tavalisse (fostamatinib)
2ms
Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer (clinicaltrials.gov)
P1, N=35, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed
Trial completion
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albumin-bound paclitaxel • Tavalisse (fostamatinib)
2ms
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease (clinicaltrials.gov)
P1, N=25, Enrolling by invitation, National Heart, Lung, and Blood Institute (NHLBI) | Not yet recruiting --> Enrolling by invitation
Enrollment open
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Tavalisse (fostamatinib)
2ms
New P1 trial
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gemcitabine • albumin-bound paclitaxel • Tavalisse (fostamatinib)
3ms
Unveiling therapeutic biomarkers and druggable targets in ALS: An integrative microarray analysis, molecular docking, and structural dynamic studies. (PubMed, Comput Biol Chem)
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.
Journal
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AURKB (Aurora Kinase B) • ABHD12 (Abhydrolase Domain Containing 12)
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Tavalisse (fostamatinib)
3ms
A Study to Assess the Safety and Efficacy of IC265 Ophthalmic Solution for Dry Eye in Adult Participants (clinicaltrials.gov)
P2, N=40, Terminated, Iacta Pharmaceuticals | In an over abundance of caution the study was terminated. All adverse events resolved with no sequelae.
Trial completion date • Trial termination • Trial primary completion date
3ms
HL-60 cells as a valuable model to study LPS-induced neutrophil extracellular traps release. (PubMed, Heliyon)
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.
Journal
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SYK (Spleen tyrosine kinase)
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Tavalisse (fostamatinib)
3ms
Syk inhibitors reduce tau protein phosphorylation and oligomerization. (PubMed, Neurobiol Dis)
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.
Journal
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SYK (Spleen tyrosine kinase)
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Tavalisse (fostamatinib) • BAY-61-3606
4ms
APTIVATE: Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1/2, N=260, Recruiting, Aptose Biosciences Inc. | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Feb 2024 --> May 2026
Trial completion date • Trial primary completion date
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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3)
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Venclexta (venetoclax) • azacitidine • tuspetinib (HM43239)
4ms
Molecular mechanisms driving the interactions between platelet and gastric cancer cells during peritoneal dissemination. (PubMed, Oncol Lett)
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.
Journal
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SYK (Spleen tyrosine kinase)
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Tavalisse (fostamatinib)
4ms
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease (clinicaltrials.gov)
P1, N=20, Not yet recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial primary completion date: Aug 2024 --> Aug 2025
Trial primary completion date
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Tavalisse (fostamatinib)
4ms
New P2 trial
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Tavalisse (fostamatinib)
4ms
A Phase II Study of SYHX1901 Tablets in the Treatment of Severe Alopecia Areata (clinicaltrials.gov)
P2, N=156, Not yet recruiting, CSPC Ouyi Pharmaceutical Co., Ltd.
New P2 trial
4ms
Fostamatinib for the Treatment of Lower-risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents (clinicaltrials.gov)
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
Trial completion • Trial completion date • Trial primary completion date
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Tavalisse (fostamatinib)
4ms
Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication. (PubMed, Cancer Res)
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.
Journal
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EGFR (Epidermal growth factor receptor) • SYK (Spleen tyrosine kinase)
5ms
Trial completion
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CRP (C-reactive protein)
5ms
Optimizing the resveratrol fragments for novel in silico hepatocellular carcinoma de novo drug design. (PubMed, Sci Rep)
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.
Journal
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FLT4 (Fms-related tyrosine kinase 4)
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Tavalisse (fostamatinib)
5ms
New P2 trial
5ms
A Study of Hutchison MediPharma Limited(HMPL)-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms (clinicaltrials.gov)
P1, N=134, Completed, Hutchison Medipharma Limited | Unknown status --> Completed | N=217 --> 134
Trial completion • Enrollment change
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sovleplenib (HMPL-523)
5ms
wAIHA: HMPL-523 (Sovleplenib) in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (clinicaltrials.gov)
P2/3, N=110, Recruiting, Hutchison Medipharma Limited | Active, not recruiting --> Recruiting
Enrollment open
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sovleplenib (HMPL-523)
5ms
Trial completion
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sovleplenib (HMPL-523)
5ms
Human Mass Balance of [14C]HMPL-523 in Healthy Adult Male Chinese Subjects (clinicaltrials.gov)
P1, N=6, Completed, Hutchmed | Active, not recruiting --> Completed | N=10 --> 6
Trial completion • Enrollment change
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sovleplenib (HMPL-523)
5ms
ESLIM-01: Phase III Study on HMPL-523 for Treatment of ITP (clinicaltrials.gov)
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
Enrollment change • Trial completion date • Trial primary completion date
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sovleplenib (HMPL-523)
6ms
A phase I study of TAK-659 and paclitaxel in patients with taxane-refractory advanced solid tumors. (PubMed, ESMO Open)
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.
P1 data • Clinical Trial,Phase I • Journal • Metastases
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SYK (Spleen tyrosine kinase)
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paclitaxel • mivavotinib (CB-659)
6ms
Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study. (PubMed, Lancet Haematol)
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.
P3 data • Journal
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SYK (Spleen tyrosine kinase)
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sovleplenib (HMPL-523)
6ms
Enrollment closed • Enrollment change
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Tavalisse (fostamatinib)
6ms
Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD (clinicaltrials.gov)
P1, N=30, Not yet recruiting, Stefanie Sarantopoulos, MD, PhD. | Initiation date: Jun 2024 --> Sep 2024
Trial initiation date
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Jakafi (ruxolitinib) • Tavalisse (fostamatinib)
7ms
Journal
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SYK (Spleen tyrosine kinase)
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Tavalisse (fostamatinib)
7ms
Study of OT202 in Treating Moderate to Severe Dry Eye (clinicaltrials.gov)
P2, N=213, Completed, Ocumension Therapeutics (Shanghai) Co., Ltd
New P2 trial
7ms
Journal
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ETV6 (ETS Variant Transcription Factor 6) • SYK (Spleen tyrosine kinase)
7ms
Discovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers. (PubMed, ACS Med Chem Lett)
Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.
Journal
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SYK (Spleen tyrosine kinase)
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sovleplenib (HMPL-523)
8ms
Dectin-1/SYK Activation Induces Antimicrobial Peptide and Negative Regulator of NF-κB Signaling in Human Oral Epithelial Cells. (PubMed, In Vivo)
Oral epithelial cells express Dectin-1 and recognize β-glucan, which activates SYK and induces the expression of antimicrobial peptides and negative regulators of NF-κB, potentially maintaining oral homeostasis.
Journal
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IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • S100A8 (S100 Calcium Binding Protein A8) • TNFAIP3 (TNF Alpha Induced Protein 3) • S100A9 (S100 Calcium Binding Protein A9) • SYK (Spleen tyrosine kinase) • CA9 (Carbonic anhydrase 9) • CLEC7A (C-Type Lectin Domain Containing 7A) • IL17A (Interleukin 17A) • IL1B (Interleukin 1, beta)
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CA9 expression • S100A9 expression
8ms
Trial completion
8ms
Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease. (PubMed, Scand J Immunol)
When the Syk expression was knocked down by its shRNA, the inhibitory effects of ISL on activated macrophages disappeared, indicating that Syk was at least one of key docking-molecules of ISL. Collectively, ISL could alleviate MCD-induced NAFLD in mice involved with the inhibition of macrophage inflammatory activity by the blockade of Syk-induced inflammasome activation.
Preclinical • Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • SYK (Spleen tyrosine kinase) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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IL6 expression
8ms
KB-LANRA- 1001: A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
P1/2, N=24, Terminated, Kronos Bio | Trial completion date: Oct 2024 --> Apr 2024 | Active, not recruiting --> Terminated; Sponsor decision
Trial completion date • Trial termination • Combination therapy
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FLT3 (Fms-related tyrosine kinase 3)
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FLT3 mutation
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Xospata (gilteritinib) • lanraplenib (GS-9876)
8ms
Enrollment open
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sovleplenib (HMPL-523)
8ms
Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy. (PubMed, Drug Resist Updat)
Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.
Journal • PARP Biomarker
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SYK (Spleen tyrosine kinase)