A randomized, placebo-controlled study to evaluate the effects of intravenous sevuparin on dermal and systemic LPS responses and the interaction between subcutaneous enoxaparin and sevuparin on coagulation responses in healthy volunteers. - Inhibition of LPS responses by sevuparin

Start Date24 Nov 2021

Sponsor / Collaborator-

ISRCTN32271864 / CompletedPhase 1IIT

Sevuparin as a potential adjunctive therapy in children with severe malaria: Phase I safety and dose-finding trial

Start Date01 Oct 2021

Sponsor / Collaborator

Imperial College London

JPRN-jRCT2031210028 / RecruitingPhase 2IIT

A Phase 2, Randomized, Double-Blind, does-finding, Parallel Group, Multi-Center Study to evaluate Efficacy and Safety of M118103 in Subjects with Prurigo nodularis.

Start Date18 Jun 2021

Sponsor / Collaborator-

100 Clinical Results associated with Heparin

100 Translational Medicine associated with Heparin

0 Patents (Medical) associated with Heparin

2,166

Literatures (Medical) associated with Heparin

01 Nov 2024·International Journal of Biological Macromolecules

Photoresponsive protamine ionic complex towards a smart hemostatic biomaterial

Article

Author: Liang, Qikai ; Chen, Jia ; Zeng, Weishen ; Zhang, Ziying ; Zhu, Shanhui ; Luo, Xiliang ; Wang, Zhen ; Wu, Quanxin ; Wu, Zhongtao ; Zhang, Lei ; Zhang, Guoqiang ; Liu, Yun

Protamine (PA) is the only licensed antidote for reversing heparin anticoagulation by electrostatically binding with heparin. Efforts have been made on designing various heparin-scavengers, while, it remains a great challenge for gaining the external-stimuli responsive PA-release material. In this study, a generic strategy is developed for fabricating photoresponsive protein materials with the designed azobenzene-containing surfactant. For the first time, based on the isomerization of azobenzene, both cationic and anionic proteins could be phase change biomaterials which are capable of transiting to isotropic state under UV irradiation at room temperature. The formation of isotropic state could set the proteins free from the binding state, activating their intrinsic biological functions. Employing this mechanism, one smart PA material for inhibiting heparin is developed, which could effectively photo-modulate the heparin concentration by turning on-and-off the free state of PA from the binding state. With good biocompatibility, the PA material addresses photoresponsive hemostatic activity in biological studies, confirming its great potential clinical values. This work provides a new designing strategy for gaining photocontrollable hemostasis materials, also opening new opportunities for developing photoresponsive protein drugs and biomedical materials.

01 Nov 2024·Biochimica et Biophysica Acta (BBA) - General Subjects

Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays

Article

Author: Musso, David L ; Smith, Ginger R ; Hughes, Mark ; Daye, Laura R ; Zheng, Weifan ; Lamson, David R ; Tarpley, Michael ; Addo, Kezia ; Ehe, Ben ; Ji, Xiaojia ; Abu Rabe, Dina ; Williams, Kevin P

Sonic hedgehog (Shh) is a morphogen with important roles in embryonic development and in the development of a number of cancers. Its activity is modulated by interactions with binding partners and co-receptors including heparin and heparin sulfate proteoglycans (HSPG). To identify antagonists of Shh/heparin binding, a diverse collection of 34,560 chemicals was screened in single point 384-well format. We identified and confirmed twenty six novel small molecule antagonists with diverse structures including four scaffolds that gave rise to multiple hits. Nineteen of the confirmed hits blocked binding of the N-terminal fragment of Shh (ShhN) to heparin with IC₅₀ values < 50 μM. In the Shh-responsive C3H10T1/2 cell model, four of the compounds demonstrated the ability to block ShhN-induced alkaline phosphatase activity. To demonstrate a direct and selective effect on ShhN ligand mediated activity, two of the compounds were able to block induction of Gli1 mRNA, a primary downstream marker for Shh signaling activity, in Shh-mediated but not Smoothened agonist (SAG)-mediated C3H10T1/2 cells. Direct binding of the two compounds to ShhN was confirmed by thermal shift assay and molecular docking simulations, with both compounds docking with the N-terminal heparin binding domain of Shh. Overall, our findings indicate that small molecule compounds that block ShhN binding to heparin and act to inhibit Shh mediated activity in vitro can be identified. We propose that the interaction between Shh and HSPGs provides a novel target for identifying small molecules that bind Shh, potentially leading to novel tool compounds to probe Shh ligand function.

01 Sep 2024·Cardiovascular Toxicology

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia

Article

Author: Ooi, Aikseng ; Pryor, Julie ; Martinez, Kiana L ; Klein, Andrew ; Steiner, Heidi E ; Karnes, Jason H ; Sweitzer, Nancy ; Giles, Jason B ; Fuchs, Deborah

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD₄₀₅] of 0.93 (SD = 1.21) units, and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD₄₀₅ ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody-negative patients. We observed statistical differences between antibody-positive and -negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody-positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

News (Medical) associated with Heparin

05 Aug 2019

·www.bioportfolio.com

Is Another Heparin Crisis Looming? Congress Raises Alarm, Demands US FDA Briefing

The FDA must explain how it will prevent heparin adulteration as a virus kills pigs in China again. Related Stories Global Regulators Caution Against Misinformation On Biosimilars The Stakes Are High So Get It Right: CHMP Oral Explanations & FDA AdComs Keeping Track: Turalio, Nubeqa And Accrufer Mark Trio Of Novel Drug Approvals

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