SY-007 / Yabao Pharma - LARVOL DELTA

Selective EPAC1 Activators Enhance Endothelial Function in Models of Vascular Inflammation. (PubMed, Pharmacol Res) - "EPAC1 activators, SY007 (EC50 = 300nM) and D-007 (EC50 = 6.76µM), effectively restored endothelial function, while endothelium-independent responses to sodium nitroprusside were unaffected. Furthermore, in a three-cell co-culture system, comprising human vascular endothelial, smooth muscle and macrophage cells, EPAC1 activators induced transcriptional reprogramming in endothelial cells, upregulating eNOS (NOS3) and downregulating pro-inflammatory mediators. These results highlight the therapeutic potential of selective EPAC1 activation for restoring endothelial function and mitigating vascular inflammation."

Journal • Atherosclerosis • Cardiovascular • Inflammation • IL6 • NOS3 • SOCS3

Non-cyclic nucleotide EPAC1 activators suppress lipopolysaccharide-regulated gene expression, signalling and intracellular communication in differentiated macrophage-like THP-1 cells. (PubMed, Cell Signal) - "This study explores the anti-inflammatory effects of non-cyclic nucleotide EPAC1 activators, PW0577 and SY007, on lipopolysaccharide (LPS)-induced responses in differentiated THP-1 macrophage-like cells...Additionally, in a co-culture model involving THP-1 macrophages, vascular smooth muscle cells, and human coronary artery endothelial cells, EPAC1 activators modulated immune-vascular interactions, suggesting a broader role in regulating cellular communication between macrophages and endothelial cells. These findings enhance our understanding of EPAC1's role in inflammation and propose EPAC1 activators as potential therapeutic agents for treating inflammatory and fibrotic conditions through targeted modulation of Rap1 and associated signalling pathways."

Journal • Fibrosis • Immunology • Inflammation • IL1B • NLRP3

SY007 - Providing access to laboratory diagnosis and surveillance in remote settings: problems and solutions (ECCMID 2024) - "This will strengthen epidemiological surveillance and contribute to containing outbreaks of emerging diseases in remote settings. In this session four practical examples of solutions for infectious disease control and surveillance in remote settings are presented."

Infectious Disease

SY007. JCEM Symposium: Advances in Treatments for Cushing Syndrome (ENDO 2023) - "Large clinical trials are evaluating new therapies directed at modulating the HPA axis, and novel targets are being identified. Targets include adrenal steroidogenesis inhibitors, GR and ACTH-Receptor antagonists and selective inhibitors of 11b-hydroxysteroid dehydrogenase type."

Endocrine Disorders

Protein interaction, cytotoxic, transcriptomic and proteomic responses to structurally distinct EPAC1 activators in HUVECs. (PubMed, Sci Rep) - "This was soon followed by the identification of the I942 analogues, PW0381, PW0521 and PWO577 and a series of benzofuran oxoacetic acid EPAC1 activators, SY006, SY007 and SY009. Together these results demonstrate the utility of structurally distinct, specific and non-toxic EPAC1 activators. Future modifications will be aimed at eliminating the few noted off-target effects."

Journal • CCL2 • ICAM1 • IL6 • IL6ST • JAK3 • MMP1 • SOCS3 • STAT3

(SY007) TIME Out: Emerging Approaches to Combat the Tumor Immunosuppressive Microenvironment in Endocrine-Related Cancers (ENDO 2022) - No abstract available

Oncology

SY007 in Patients With Acute Ischemic Stroke (clinicaltrials.gov) - P1 | N=36 | Suspended | Sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd. | Trial completion date: Dec 2022 ➔ Dec 2023 | Not yet recruiting ➔ Suspended | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Trial suspension • Cardiovascular • Ischemic stroke

(SY007) TIME Out: Emerging Approaches to Combat the Tumor Immunosuppressive Microenvironment in Endocrine-Related Cancers - Immune cell work in ACC (ENDO 2022) - No abstract available

Oncology

(SY007) Symposium TIME Out: Emerging Approaches to Combat the Tumor Immunosuppressive Microenvironment in Endocrine-Related Cancers (ENDO 2022) - No abstract available

Oncology

(SY007) TIME Out: Emerging Approaches to Combat the Tumor Immunosuppressive Microenvironment in Endocrine-Related Cancers - Understanding tumor immune niche to treat cancer (ENDO 2022) - No abstract available

Oncology

(SY007) TIME Out: Emerging Approaches to Combat the Tumor Immunosuppressive Microenvironment in Endocrine-Related Cancers - Progesterone Receptor Regulation of Interferon Signaling in Breast Cancer (ENDO 2022) - No abstract available

Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • PGR

First-in-human safety, tolerability, and pharmacokinetics of SY-007, a prolonged action neuroprotective drug for ischemic stroke, in healthy Chinese subjects. (PubMed, Eur J Pharm Sci) - P1 | "Intravenous dosing of SY-007 appears to be safe up to a dose of 60 mg. Nonlinear pharmacokinetics was observed across the evaluated doses and TMDD might be the primary reason. The effective dose of SY-007 for neuroprotective effect in patients with ischemic stroke is expected to be 10-30 mg and was recommended for the later multiple ascending dose study of SY-007."

Clinical • Journal • P1 data • PK/PD data • Cardiovascular • Ischemic stroke • PTEN

SY007 in Patients With Acute Ischemic Stroke (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd.

Clinical • New P1 trial • Cardiovascular • Ischemic stroke

Single-dose Incremental Intravenous Injection of SY-007 in Healthy Subjects (clinicaltrials.gov) - P1; N=78; Completed; Sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd.; Recruiting ➔ Completed; Trial completion date: Dec 2020 ➔ May 2020

Clinical • Trial completion • Trial completion date

Single-dose Incremental Intravenous Injection of SY-007 in Healthy Subjects (clinicaltrials.gov) - P1; N=66; Recruiting; Sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd.; Trial completion date: Apr 2020 ➔ Dec 2020; Trial primary completion date: Dec 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date