- |||||||||| lenumlostat (GB2064) / Galecto
Journal: LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension. (Pubmed Central) - Sep 21, 2024 Hypoxia induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH, as well as pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 could be a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH.
- |||||||||| GB1107 / Galecto
Journal: Myocardin related transcription factor and galectin-3 drives lipid accumulation in human blood vessels. (Pubmed Central) - Sep 9, 2024 Ex vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.
- |||||||||| lenumlostat (GB2064) / Galecto, semaxanib (SU5416) / Pfizer
LOXL2 Inhibition Rescues Pulmonary Hypertension-Induced Right Ventricular Failure (119AB) - Jun 25, 2024 - Abstract #ASA2024ASA_1293; Our RV transcriptomic analysis of PAH patients and animal models revealed a novel mechanism involving LOXL2 in PAH-induced RV failure. We propose a potential therapeutic strategy where blockade of LOXL2 can rescue RV failure by attenuation of fibrosis.
- |||||||||| lenumlostat (GB2064) / Galecto, semaxanib (SU5416) / Pfizer
LOXL2 Inhibition Rescues Pulmonary Hypertension-Induced Right Ventricular Failure (Exhibit Hall) - Jun 25, 2024 - Abstract #ASA2024ASA_49; Our RV transcriptomic analysis of PAH patients and animal models revealed a novel mechanism involving LOXL2 in PAH-induced RV failure. We propose a potential therapeutic strategy where blockade of LOXL2 can rescue RV failure by attenuation of fibrosis.
- |||||||||| olitigaltin (GB0139) / Galecto
Journal: Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release. (Pubmed Central) - Mar 8, 2024 Because the activation conditions of conventional glycosyl donors and our CCPB thioglycoside are orthogonal, our novel donor is amenable to controlled one-pot glycosylation reactions with conventional donors for expeditious access to complex glycans. The strain-release glycosylation is applied to the assembly of a tetrasaccharide of O-polysaccharide of Escherichia coli O-33 in one pot and the synthesis of a 1,1'-S-linked glycoside oral galectin-3 (Gal-3) inhibitor, TD139, to demonstrate the versatility and effectiveness of the novel method for constructing both O- and S-glycosides.
- |||||||||| GB1107 / Galecto
Journal: Discovery of Selective and Orally Available Galectin-1 Inhibitors. (Pubmed Central) - Dec 7, 2023 High affinity and specificity were achieved by changing six-membered aryl-triazolyl substituents in a series of recently published galectin-3-selective ?-d-thiogalactosides (e.g., GB1107 K galectin-1/3 3.7/0.037 ?M) for five-membered heterocycles such as thiazoles...No cell cytotoxicity was observed for GB1490 up to 90 ?M in the A549 cells. In pharmacokinetic studies in mice, GB1490 showed high oral bioavailability (F% > 99%).
- |||||||||| olitigaltin (GB0139) / Galecto
Trial completion date, Trial primary completion date: DEFINE - Evaluating Therapies for COVID-19 (clinicaltrials.gov) - Dec 4, 2023 P1/2, N=200, Recruiting, In pharmacokinetic studies in mice, GB1490 showed high oral bioavailability (F% > 99%). Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
- |||||||||| selvigaltin (GB1211) / Galecto
Trial completion: GALBA-1: A Study to Compare Pharmacokinetics of GB1211 (clinicaltrials.gov) - Sep 1, 2023 P1, N=13, Completed, Reversal of this effect with the clinical candidate GB1211 offers a potential enhancing combination therapeutic with anti-PD-1 and -PD-L1 blocking antibodies. Active, not recruiting --> Completed
- |||||||||| olitigaltin (GB0139) / Galecto
Review, Journal: Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy. (Pubmed Central) - Jul 29, 2023 Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest...We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed.
- |||||||||| LYT-200 / PureTech, GB1211 / Galecto
Review, Journal: Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy. (Pubmed Central) - Jul 2, 2023 Other galectin members are also included in this review to provide insight into potential candidates for future treatment(s). The pitfalls and limitations of using galectins and their inhibitors are also discussed to cognise their clinical application.
- |||||||||| olitigaltin (GB0139) / Galecto
Journal: Role of galectin-3 in cardiac dysfunction induced by subarachnoid hemorrhage. (Pubmed Central) - May 22, 2023 Additionally, when macrophage activation was suppressed using the beta-blocker propranolol, cardiac function improved, and galectin-3 expression in the cardiac tissue decreased. Collectively, our findings offer new insights into the role of galectin-3 in SAH-related cardiac dysfunction and suggest a macrophage-galectin-3 axis as a potential therapeutic strategy.
- |||||||||| selvigaltin (GB1211) / Galecto
Trial primary completion date: GALBA-1: A Study to Compare Pharmacokinetics of GB1211 (clinicaltrials.gov) - May 8, 2023 P1, N=12, Active, not recruiting, Figure: Bone Marrow Fibrosis, Myelofibrosis, Janus Kinase inhibitor, Clinical trial Trial primary completion date: Mar 2023 --> Jun 2023
- |||||||||| lenumlostat (GB2064) / Galecto
Enrollment closed, Trial completion date, Trial primary completion date: MYLOX-1: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 in Participants With Myelofibrosis (clinicaltrials.gov) - May 6, 2023 P2a, N=21, Active, not recruiting, Trial primary completion date: Mar 2023 --> Jun 2023 Recruiting --> Active, not recruiting | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| selvigaltin (GB1211) / Galecto
Enrollment closed: GALBA-1: A Study to Compare Pharmacokinetics of GB1211 (clinicaltrials.gov) - Mar 23, 2023 P1, N=12, Active, not recruiting, Results GB0139 caused a concentration-dependent reduction in Gal-3 in IPF PCLuS (0.3-10 Recruiting --> Active, not recruiting
- |||||||||| GB2064 / Galecto
Mylox-1: An Open-Label, Phase IIa Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral LOXL2 Inhibitor, GB2064, in Myelofibrosis (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2540; These results suggested that Galectin-3 inhibition may exert a protective role against the neurocognitive dysfunction associated with OSA. MYLOX-1 is designed to explore the safety and clinical effects of GB2064, a novel small-molecule LOXL-2 inhibitor, addressing bone marrow fibrosis as a main element of MF, with the aim to decrease extramedullary haematopoiesis and improve haematological parameters, symptom burden and the quality of life for patients with MF.
- |||||||||| olitigaltin (GB0139) / Galecto
Enrollment open, Trial completion date, Trial primary completion date: DEFINE - Evaluating Therapies for COVID-19 (clinicaltrials.gov) - Nov 2, 2022 P1/2, N=200, Recruiting, The observed reduction of transaminases and CAP indicate a decrease in liver inflammation and a potential effect on steatosis which, in combination with the reduction in VCTE, prompt further exploration of anti-fibrotic effects and clinical benefit. Active, not recruiting --> Recruiting | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| GB1211 / Galecto, GB0139 / Galecto
Journal: Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease. (Pubmed Central) - Oct 15, 2022 Further characterization showed that this class of compounds reduced profibrotic gene expression in liver myofibroblasts and displayed antifibrotic activity in CCl-induced liver fibrosis and bleomycin-induced lung fibrosis mouse models. On the basis of the overall pharmacokinetic, pharmacodynamic, and safety profile, GB1211 was selected as the clinical candidate and is currently in phase IIa clinical trials as a potential therapy for liver cirrhosis and cancer.
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