Delving into the Latest Updates on SAJE Pharma LLC with Synapse

Overview

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Other Diseases

Immune System Diseases

Digestive System Disorders

Small molecule drug

Chemical drugs

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Immune System Diseases	3
Endocrinology and Metabolic Disease	2
Nervous System Diseases	2
Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	4
Chemical drugs	1

Top 5 Target	Count

GSNOR(alcohol dehydrogenase 5 (class III), chi polypeptide)	3

Author: Ichinose, Fumito ; Donnino, Michael W. ; Mori, Naohiro ; Malhotra, Rajeev ; Bagchi, Aranya ; Hirai, Shuichi ; Marutani, Eizo ; Stamler, Jonathan S. ; Berra, Lorenzo ; Bradley, Matthews O. ; Magliocca, Aurora ; Hayashida, Kei ; Miyazaki, Yusuke ; Rezoagli, Emanuele ; Seth, Divya ; Liu, Xiaowen ; Hindle, Allyson G. ; Silverman, Michael G.

Background:The biological effects of nitric oxide are mediated via protein S-nitrosylation. Levels of S-nitrosylated protein are controlled in part by the denitrosylase, S-nitrosoglutathione reductase (GSNOR). The objective of this study was to examine whether GSNOR inhibition improves outcomes after cardiac arrest and cardiopulmonary resuscitation (CA/CPR).Methods: Adult wild-type C57BL/6 and GSNOR-deleted (GSNOR −/− ) mice were subjected to potassium chloride-induced CA and subsequently resuscitated. Fifteen minutes after a return of spontaneous circulation, wild-type mice were randomized to receive the GSNOR inhibitor, SPL-334.1, or normal saline as placebo. Mortality, neurological outcome, GSNOR activity, and levels of S-nitrosylated proteins were evaluated. Plasma GSNOR activity was measured in plasma samples obtained from post-CA patients, preoperative cardiac surgery patients, and healthy volunteers. Results: GSNOR activity was increased in plasma and multiple organs of mice, including brain in particular. Levels of protein S-nitrosylation were decreased in the brain 6 hours after CA/CPR. Administration of SPL-334.1 attenuated the increase in GSNOR activity in brain, heart, liver, spleen, and plasma, and restored S-nitrosylated protein levels in the brain. Inhibition of GSNOR attenuated ischemic brain injury and improved survival in wild-type mice after CA/CPR (81.8% in SPL-334.1 versus 36.4% in placebo; log rank P =0.031). Similarly, GSNOR deletion prevented the reduction in the number of S-nitrosylated proteins in the brain, mitigated brain injury, and improved neurological recovery and survival after CA/CPR. Both GSNOR inhibition and deletion attenuated CA/CPR-induced disruption of blood brain barrier. Post-CA patients had higher plasma GSNOR activity than did preoperative cardiac surgery patients or healthy volunteers ( P <0.0001). Plasma GSNOR activity was positively correlated with initial lactate levels in postarrest patients (Spearman correlation coefficient=0.48; P =0.045). Conclusions:CA and CPR activated GSNOR and reduced the number of S-nitrosylated proteins in the brain. Pharmacological inhibition or genetic deletion of GSNOR prevented ischemic brain injury and improved survival rates by restoring S-nitrosylated protein levels in the brain after CA/CPR in mice. Our observations suggest that GSNOR is a novel biomarker of postarrest brain injury as well as a molecular target to improve outcomes after CA.

100 Deals associated with SAJE Pharma LLC

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100 Translational Medicine associated with SAJE Pharma LLC

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

5

3

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

SPL-891 ( GSNOR )	Neoplasms More	Preclinical
SPL-850 ( GSNOR )	Inflammation More	Preclinical
SPL-334.1 ( GSNOR )	Asthma More	Preclinical
SPL-889	Inflammation More	Preclinical
SPL-890	Inflammation More	Preclinical