Delving into the Latest Updates on SelK-2 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti P-selectin glycoprotein ligand-1, Anti-PSGL-1-mAb

Target

PSGL-1

Action

inhibitors

Mechanism

PSGL-1 inhibitors(P-selectin glycoprotein ligand-1 inhibitors)

Therapeutic Areas

Immune System DiseasesCardiovascular DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

AsthmaPulmonary Disease, Chronic ObstructiveThrombosis+ [1]

Originator Organization

Selexys Pharmaceuticals Corp.

Active Organization-

Inactive Organization

Tetherex Pharmaceuticals Corp.Startup

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 1058255138L

Source: *****

Sequence Code 1058255137H

Source: *****

A Two Part, Randomised, Double-blind, Placebo-controlled, Phase 2 Parallel Group Study to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 on Airway Responses Following Allergen Challenge in Subjects With Asthma (Part 1) and to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 in Subjects With Chronic Obstructive Pulmonary Disease (Part 2)

This study has two parts. The main purpose of Part 1 of this study will be to examine how safe and effective two doses of SelK2 is on participants with mild asthma. Lung function and inflammatory cell numbers will be measured in response to the administration of an allergen (a compound to which the participant is allergic) into the lungs in the presence or absence of SelK2. Part 2 of this study will examine how safe and effective one dose of SelK2 is on participants with chronic obstructive pulmonary disease (COPD). Lung function and inflammatory cell numbers will be measured in COPD patients in the presence or absence of SelK2. SelK2 may block the movement of key inflammatory cells into the lungs and consequently improve lung function in these two patient populations.

Start Date18 Aug 2020

Sponsor / Collaborator

Tetherex Pharmaceuticals Corp.Startup

NCT03812328

/ CompletedPhase 2

A Phase 2, Randomized, Active Comparator-Controlled, Open-Label, Adaptive Design Study to Assess the Safety and Efficacy of Intravenously-Administered SelK2 in Patients Undergoing Total Knee Arthroplasty

The main purpose of this study is to determine if an investigational medication called SelK2 works in preventing a condition called "venous thromboembolism" (VTE) in patients having a total knee replacement. SelK2 has been designed to attach to a protein found on blood cells and blood vessels. By attaching to this protein, SelK2 is designed to decrease the inflammatory process in the blood vessel wall that leads to the formation of blood clots in the vessel (called thrombosis). By decreasing the inflammatory process, SelK2 may reduce the risk of VTE following joint replacement surgery. In addition, because SelK2 is not a blood thinner, it is expected that the risk for bleeding will also be reduced.

Start Date20 Feb 2019

Sponsor / Collaborator

Tetherex Pharmaceuticals Corp.Startup

100 Clinical Results associated with SelK-2

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100 Translational Medicine associated with SelK-2

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100 Patents (Medical) associated with SelK-2

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3

Literatures (Medical) associated with SelK-2

01 Nov 2023·Acta Pharmaceutica Sinica B

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Article

Author: Xu, Jianqing ; Li, Yuhan ; Yang, Zhiwei ; Yang, Yuhui ; Ding, Xiangqing ; Su, Jianrong ; Zhang, Xu ; Jiang, Xiaoliang ; Liu, Xing ; Wu, Xianxian ; Ding, Longfei

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

01 Apr 2012·Vox SanguinisQ4 · MEDICINE

Adhesive interaction between peripheral blood mononuclear cells and activated platelets in the presence of anti‐human leukocyte antigen Class I alloantibody causes production of IL‐1β and IL‐8

Q4 · MEDICINE

Article

Author: M. Fujihara ; H. Ikeda ; D. Takahashi ; T. Kato ; H. Azuma ; S. Wakamoto ; S. Sato

Background: Activated platelets form heterogeneous aggregates of platelets and monocytes, which are involved in a variety of inflammatory disorders. Some anti‐human leukocyte antigen (HLA) Class I antibodies have been shown to activate platelets.Materials and Methods: Human leukocyte antigen‐A2‐positive or HLA‐A2‐negative platelets were incubated with HLA‐A2‐negative peripheral blood mononuclear cells (PBMNCs) in the presence of anti‐HLA‐A2 serum at 37°C. The binding of platelets to monocytes was analysed by flow cytometry. The levels of IL‐1 β and IL‐8 in the culture supernatant were determined by ELISA.Results: Anti‐HLA‐A2 serum increased the formation of aggregates between monocytes and HLA‐A2‐positive platelets, but not HLA‐A2‐negative platelets, in a dose‐dependent manner. Antiserum also increased the number of platelets bound to monocytes in a time‐dependent manner. The addition of anti‐P‐selectin glycoprotein ligand (PSGL‐1) mAb almost completely inhibited the formation of platelet–monocyte aggregates as well as the number of platelets bound to monocytes. When HLA‐A2‐positive or HLA‐A2‐negative platelets were incubated with HLA‐A2‐negative PBMNCs in the presence of anti‐HLA‐A2, the level of IL‐1β and IL‐8 in the supernatant of coculture was significantly higher in HLA‐A2‐positive platelets than in HLA‐A2‐negative platelets. The addition of anti‐PSGL‐1 mAb partially but significantly inhibited the production of both IL‐1β and IL‐8.Conclusions: The activation of platelets with anti‐HLA Class I alloantibody caused the formation of platelet–monocyte aggregates, followed by the production of IL‐1β and IL‐8, in a cognate antigen–antibody manner. The adhesive interaction of P‐selectin and PSGL‐1 at least partially contributed to these phenomena.

29 Nov 2004·Journal of Leukocyte BiologyQ3 · MEDICINE

Blockade of PSGL-1 attenuates CD14+ monocytic cell recruitment in intestinal mucosa and ameliorates ileitis in SAMP1/Yit mice

Q3 · MEDICINE

Article

Author: Itoh, Kazuro ; Kawaguchi, Atsushi ; Matsunaga, Hisayuki ; Nagao, Shigeaki ; Tsuzuki, Yoshikazu ; Miyazaki, Junichi ; Hokari, Ryota ; Matsuzaki, Koji ; Matsumoto, Satoshi ; Okada, Yoshikiyo ; Miura, Soichiro ; Inoue, Takuya

AbstractThe pathogenesis of Crohn's disease (CD) is not known. However, monocytes and macrophages are thought to play important roles in the development of mucosal inflammation. Therefore, in this study, we examined the role of monocyte-endothelial cell interactions in senescence-accelerated mouse P1 (SAMP1)/Yit mice, a murine model of spontaneous ileitis. Fluorescence-labeled CD14+ monocytic cells isolated from the spleen and mesenteric lymph nodes of AKR/J (control) mice were injected into the tail veins of recipient (AKR/J and SAMP1/Yit) mice, and migration in the postcapillary venules (PCV) of Peyer's patches, submucosal venules, and villus microvessels of the terminal ileum was monitored by using an intravital microscope. Rolling and adhesion of CD14+ monocytic cells in the PCV of Peyer's patches and microvessels of the terminal ileum were increased in SAMP1/Yit mice. An imunohistochemical study showed increased expression of P-selectin glycoprotein-1 (PSGL-1), P-selectin, and vascular cell adhesion molecule-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against these three adhesion molecules significantly inhibited adhesion of CD14+ monocytic cells to the PCV of Peyer's patches and microvessels of the terminal ileum, treatment with an anti-PSGL-1 monoclonal antibody (mAb) showing the strongest suppressive effect. Anti-PSGL-1 mAb also attenuated T cell adhesion in microvessels of intestinal mucosa. In addition, periodical administration of an anti-PSGL-1 mAb for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice. The results suggest that PSGL-1-P-selectin interaction plays an important role in monocyte-endothelial cell interactions and the development of ileitis in a murine model of CD and that the blockade of this adhesion molecule may be a novel strategy for treating CD.

100 Deals associated with SelK-2

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Thrombosis	Phase 2	Bulgaria	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Thrombosis	Phase 2	Poland	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Thrombosis	Phase 2	Lithuania	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Thrombosis	Phase 2	Ukraine	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Thrombosis	Phase 2	Latvia	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Venous Thromboembolism	Phase 2	Ukraine	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Venous Thromboembolism	Phase 2	Latvia	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Venous Thromboembolism	Phase 2	Poland	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Venous Thromboembolism	Phase 2	Bulgaria	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019
Venous Thromboembolism	Phase 2	Lithuania	Tetherex Pharmaceuticals Corp.Startup	20 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03812328 (COURSE, CTgov)	Phase 2	Thrombosis \| Venous Thromboembolism	207	SelK2 (SelK2)	cefobmwlaf(qxoklqqfdz) = fzxaarrzah fivpxqewqv (yuhysgkprq, vwdttytmbz - soewyzwdkl) View more	-	24 Nov 2020
				SelK2+Enoxaparin (SelK2 and Enoxaparin)	cefobmwlaf(qxoklqqfdz) = jktuttjbdg fivpxqewqv (yuhysgkprq, fmuatotlrn - vjaoyzyzla) View more

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Biosimilar

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