Delving into the Latest Updates on WS-635 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

+ [2]

Target

CYPA

Mechanism

CYPA inhibitors(Cyclophilin A inhibitors)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Emergence Delirium

Inactive Indication

Chronic hepatitis C genotype 1

Originator Organization

SCYNEXIS, Inc.

Active Organization

Waterstone Pharmaceuticals (Wuhan) Co., Ltd.

Inactive Organization

SCYNEXIS, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC66H120N12O13S

InChIKeyAQHMBDAHQGYLIU-XNFHFXFQSA-N

CAS Registry210759-10-7

Sequence Code 13759700

This study will examine the effectiveness of 28 days of triple combination therapy including SCY-635 with peginterferon alfa 2a and ribavirin in reducing serum HCV RNA levels. An additional 20 weeks of treatment with the currently approved standard of care will be offered to all participants. The Week 24 visit will be the last on-study visit. After the Week 24 visit, all subjects with undetectable HCV RNA will be given the option to continue treatment with standard of care for an additional 24 weeks (out to Week 48) under the care of their Principal Investigator.

Start Date01 Nov 2010

Sponsor / Collaborator

SCYNEXIS, Inc.

NCT01290965

/ CompletedPhase 1

A Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics, and Effect of Treatment With SCY 635 on Plasma HCV RNA Following 15 Days of Oral Administration in Adult Patients With Chronic Hepatitis C Infection

This study will examine the effectiveness of 15 days of therapy with SCY-635 in reducing hepatitis C virus (HCV) RNA levels.

Start Date01 Apr 2007

Sponsor / Collaborator

SCYNEXIS, Inc.

100 Clinical Results associated with WS-635

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100 Translational Medicine associated with WS-635

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100 Patents (Medical) associated with WS-635

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16

Literatures (Medical) associated with WS-635

01 Sep 2023·Alzheimer's & Dementia

Blood tau‐PT217 contributes to the anesthesia/surgery‐induced delirium‐like behavior in aged mice

Article

Author: Zhang, Yiying ; Liu, Chenghao ; Culley, Deborah J. ; Lu, Jing ; Xu, Miao ; Yang, Guang ; Liang, Feng ; Crosby, Gregory ; Dong, Yuanlin ; Xie, Zhongcong ; Bai, Ping ; Shen, Yuan ; Khatri, Ashok ; Marcantonio, Edward ; Quan, Qimin ; Tian, Wenjie ; Wang, Changning ; Sun, Zhengwang

AbstractINTRODUCTIONBlood phosphorylated tau at threonine 217 (tau‐PT217) is a newly established biomarker for Alzheimer's disease and postoperative delirium in patients. However, the mechanisms and consequences of acute changes in blood tau‐PT217 remain largely unknown.METHODSWe investigated the effects of anesthesia/surgery on blood tau‐PT217 in aged mice, and evaluated the associated changes in B cell populations, neuronal excitability in anterior cingulate cortex, and delirium‐like behavior using positron emission tomography imaging, nanoneedle technology, flow cytometry, electrophysiology, and behavioral tests.RESULTSAnesthesia/surgery induced acute increases in blood tau‐PT217 via enhanced generation in the lungs and release from B cells. Tau‐PT217 might cross the blood–brain barrier, increasing neuronal excitability and inducing delirium‐like behavior. B cell transfer and WS635, a mitochondrial function enhancer, mitigated the anesthesia/surgery‐induced changes.DISCUSSIONAcute increases in blood tau‐PT217 may contribute to brain dysfunction and postoperative delirium. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.

01 Mar 2021·Acta Pharmaceutica Sinica BQ1 · CHEMISTRY

A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors

Q1 · CHEMISTRY

ArticleOA

Author: Yu, Bin ; Wu, Yahong ; Liu, Hong-Min ; Zhao, Min ; Song, Yihui

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC₅₀ = 0.32 μmol/L; WS-635: IC₅₀ = 4.13 μmol/L) and thus represent novel scaffolds for designing new SHP2-PTP inhibitors. TK-147, an allosteric inhibitor, inhibited SHP2 potently (IC₅₀ = 0.25 μmol/L). In structure, TK-147 could be regarded as a bioisostere of the well characterized SHP2 inhibitor SHP-099, highlighting the essential structural elements for allosteric inhibition of SHP2. The principle underlying the cross-validation protocol is potentially feasible to identify allosteric inhibitors or those inactivating mutants of other proteins.

11 Sep 2014·Journal of Medicinal ChemistryQ1 · MEDICINE

From Chemical Tools to Clinical Medicines: Nonimmunosuppressive Cyclophilin Inhibitors Derived from the Cyclosporin and Sanglifehrin Scaffolds

Q1 · MEDICINE

Article

Author: Sweeney, Zachary K. ; Wiedmann, Brigitte ; Fu, Jiping

The cyclophilins are widely expressed enzymes that catalyze the interconversion of the cis and trans peptide bonds of prolines. The immunosuppressive natural products cyclosporine A and sanglifehrin A inhibit the enzymatic activity of the cyclophilins. Chemical modification of both the cyclosporine and sanglifehrin scaffolds has produced many analogues that inhibit cyclophilins in vitro but have reduced immunosuppressive properties. Three nonimmunosuppressive cyclophilin inhibitors (alisporivir, SCY-635, and NIM811) have demonstrated clinical efficacy for the treatment of hepatitis C infection. Additional candidates are in various stages of preclinical development for the treatment of hepatitis C or myocardial reperfusion injury. Recent publications suggest that cyclophilin inhibitors may have utility for the treatment of diverse viral infections, inflammatory indications, and cancer. In this review, we document the structure-activity relationships of the nonimmunosuppressive cyclosporins and sanglifehrins in clinical and preclinical development. Aspects of the pharmacokinetic behavior and chemical biology of these drug candidates are also described.

100 Deals associated with WS-635

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12451

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic hepatitis C genotype 1	Phase 3	PR	SCYNEXIS, Inc.	01 Nov 2010
Chronic hepatitis C genotype 1	Phase 3	US	SCYNEXIS, Inc.	01 Nov 2010
Emergence Delirium	Phase 1	CN	Waterstone Pharmaceuticals (Wuhan) Co., Ltd.	18 Oct 2024

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01265511 (CTgov)	Phase 2	Chronic hepatitis C genotype 1	10	Placebo+Pegasys (Placebo)	vsrxegftoz(soxmhcwfgr) = ftxlhvthqj onxzqanbzw (punuaxakor, ktogrbghpc - fzncmxgejm) View more	-	18 Aug 2017
				SCY-635+Pegasys (SCY-635 600 mg)	vsrxegftoz(soxmhcwfgr) = blvzaatleb onxzqanbzw (punuaxakor, iqwzvwcmdb - hvhrqwogja) View more