SP-8356 / Shin Poong Pharma - LARVOL DELTA

EMMPRIN aggravates angiogenesis and blood-retina barrier injury by regulating matrix metalloproteinases in diabetic retinopathy. (PubMed, Diab Vasc Dis Res) - "Western blotting or RT-qPCR was performed to measure protein or mRNA levels of MMPs, tight junction factors, and angiogenic factors. High EMMPRIN levels were found in both serum and vitreous samples of DR rats. Inhibition of EMMPRIN using SP-8356 ameliorated DR-induced high levels of inflammatory cytokines, MMPs, and angiogenic factors and rescued DR-induced low expression levels of tight junction factors in rat vitreous samples. EMMPRIN accelerates inflammation, angiogenesis and blood-retina barrier injury in DR by regulating MMPs."

Journal • Diabetes • Diabetic Retinopathy • Inflammation • Metabolic Disorders • Retinal Disorders • BSG

LETM-domain containing 1 (LETMD1) protects against obesity via enhancing UCP1-independent energy expenditure in human beige adipocytes. (PubMed, Theranostics) - "Furthermore, human beige adipocytes harboring a doxycycline-inducible LETMD1 expression cassette were transplanted to NOD/SCID mice and the function of LETMD1 in human beige adipocytes was evaluated in the in vivo setting. Oral administration of SP-8356 induced genes related to UCP1-independent energy expenditure in beige adipocytes, and counteracted body weight gain and metabolic disorders in mice. Increased LETMD1 action, either genetically or pharmacologically, enhances the non-canonical UCP1-independent energy expenditure in beige adipocytes."

Journal • Genetic Disorders • Metabolic Disorders • Obesity • Transplantation • PPARGC1A

The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model. (PubMed, Int J Mol Sci) - "These potent cytoprotective effects of SP-8356 were achieved by suppressing the excessive production of free radicals and pro-inflammatory cytokines, reducing the infiltration of inflammatory cells, and mitigating increases in blood-brain barrier permeability. Additional research is needed to determine whether co-administration of SP-8356 can extend the therapeutic time window of reperfusion therapies by mitigating ischemia/reperfusion injury."

Journal • Preclinical • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Reperfusion Injury • Vascular Neurology

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration. (PubMed, Int Immunopharmacol) - "By reducing immune cell infiltration into inflamed lung tissue, SP-8356 exerted a broad protective effect against ALI. These findings position SP-8356 as a promising therapeutic candidate for pulmonary inflammatory diseases that cause ALI."

Immune cell • Journal • Acute Lung Injury • Inflammation • Respiratory Diseases

SP-8356: A Novel Verbenone Derivative Exerts In Vitro Anti-Non-Small Cell Lung Cancer Effects, Promotes Apoptosis via The P53/MDM2 Axis and Inhibits Tumor Formation in Mice. (PubMed, Cell J) - "Our findings shed light on the molecular mechanisms underlying anticancer activity of SP-8356 and highlight its potential as a promising therapeutic candidate for NSCLC treatment."

IO biomarker • Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BAX • BCL2 • CCNB1 • CDK1 • TP53

Clathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis. (PubMed, J Extracell Vesicles) - "Last, SP-8356 alone or in combination with sorafenib attenuated PDXs growth. The study reveals the role of HCC derived sEV-CLTA in microvascular niche formation. Inhibition of CLTA and its mediated pathway may illuminate a new therapeutic strategy for HCC patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • BSG

SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation. (PubMed, Cell J) - "SP-8356 was found to inhibit proliferation, suppressed cells migration and invasion and decreased OS tumor growth. Furthermore, SP-8356 was found to act through PGC-1α/TFAM and AMPK activations. SP-8356 can be therefore used as therapeutic agent for OS treatment."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • TFAM

Intervention with extracellular matrix metalloproteinase inducer in osteoclasts attenuates periodontitis-induced bone resorption. (PubMed, Odontology) - "Both EMMPRIN-positive and MMP-9-positive osteoclasts were less common in the EMMPRIN inhibitor groups than in the control groups. Intervention of EMMPRIN signaling in osteoclasts could probably provide a potential therapeutic target for attenuating ligation-induced bone resorption."

Journal • Dental Disorders • Inflammation • Periodontitis • BSG • CD68 • MMP9 • TRAP

A Phase I Study to Evaluate Safety and Pharmacokinetics of Escalating Single Doses and Multiple Doses of SP-8356 (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: Shin Poong Pharmaceutical Co. Ltd.

New P1 trial • Atherosclerosis • Cardiovascular • Dyslipidemia • Ischemic stroke

Therapeutic effect of SP-8356 on pulmonary embolism-associated cardiac injury is mediated by its ability to suppress apoptosis and inflammation. (PubMed, J Cell Mol Med) - "Furthermore, SP-8536 significantly restored the up-regulation of MMP-9, p-ERK1/2, p-P65, CyA protein and the cellular apoptosis in the PE rat model. Our study validated that SP-8356 could suppress cell apoptosis and inflammatory response via down-regulating the highly expressed MMP-9, p-ERK1/2, and p-P65 and MMP-9 in PE-associated cardiac injury in a dose-dependent manner."

Journal • Cardiovascular • Immunology • Inflammation • Pneumonia • Pulmonary Embolism • Respiratory Diseases • MMP9 • MPO • RELA

SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling. (PubMed, Biomol Ther (Seoul)) - "Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation."

Journal • Gastrointestinal Cancer • Hepatitis B • Hepatitis C Virus • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cancer • Oncology • Solid Tumor

SP-8356, a (1S)-(-)-verbenone derivative, exerts in vitro and in vivo anti-breast cancer effects by inhibiting NF-κB signaling. (PubMed, Sci Rep) - "Functional studies revealed that SP-8356 suppressed serum response element-dependent reporter gene expression and NF-κB-related signaling, resulting in downregulation of many genes related to cancer invasion. We conclude that SP-8356 suppresses breast cancer progression through multimodal functions, including inhibition of NF-κB signaling and growth-related signaling pathways."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

A novel CD147 inhibitor, SP-8356, reduces neointimal hyperplasia and arterial stiffness in a rat model of partial carotid artery ligation. (PubMed, J Transl Med) - "The ability of SP-8356 to reduce neointimal hyperplasia and improve arterial stiffness in affected carotid artery suggests that SP-8356 could be a promising therapeutic drug for vascular remodeling disorders involving neointimal hyperplasia and arterial stiffness."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia

SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice. (PubMed, Int J Mol Sci) - "SP-8356 exerts remarkable anti-atherosclerotic effects by suppressing plaque development and improving plaque stability through inhibiting CD147-CypA interactions. Our novel findings support the potential utility of SP-8356 as a therapeutic agent for atherosclerotic plaque."

Journal • Preclinical

A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea. (PubMed, Int J Mol Sci) - "Similar to SP-8356, topical corticosteroid (prednisolone acetate, PA) also reduced the ECM-related products and opacification. In conclusion, SP-8356 is capable enough to prevent corneal haze by preventing pathological fibrosis after severe corneal damage. Therefore, SP-8356 could be a potentially promising therapeutic drug for corneal fibrosis."

Journal • Preclinical • Fibrosis • Immunology • Ophthalmology • CD14 • MMP9

Metabolism and Pharmacokinetics of SP-8356, a Novel (1S)-(-)-Verbenone Derivative, in Rats and Dogs and Its Implications in Humans. (PubMed, Molecules) - "In summary, rapid phase II metabolism appears to be mainly responsible for its suboptimal pharmacokinetics, such as high CL and low oral absorption. Because of competing metabolic reactions, potential safety risks related to SP-8356 bioactivation may be low."

Journal • PK/PD data • Preclinical

A novel CD147 inhibitor SP-8356 attenuates plaque progression and stabilizes vulnerable plaque in ApoE-deficient mice (ESC 2019) - "Owing to its improvement of plaque stability and inhibitory effect on plaque development, SP-8356 could be a potential therapeutic drug candidate for atherosclerosis and related clinical manifestations."

Preclinical