PLATFORM TECHNOLOGY

ENDOTHELIAL DYSFUNCTION

ENDOTHELIAL DYSFUNCTION

Vascular endothelial dysfunction is an early pathogenesis factor in cardiovascular disease, consisting of impaired vasodilation, angiogenesis, and barrier dysfunction. Vascular endothelial dysfunction is associated with metabolic diseases such as diabetes, obesity, or metabolic syndrome, which are linked to cardiovascular disease. Oxidative stress and inflammation play a major role in the pathogenesis of blood and endothelial dysfunction.

Endothelial dysfunction in aging & vascular associated diseases

Endothelial dysfunction-related diseases
  • DM-associated vascular diseases
    Diabetic macular edema
    Diabetic retinopathy
    Diabetic nephropathy
  • Neurovascular diseases(Eye & Brain)
    Age-related Macular Degeneration
    Dementia, etc. related with neurovascular abnormalities
  • Intractable
    inflammatory diseases
    Ulcerative colitis
  • Others
    Cancer
    immunotherapyenhancer
    I/R injury
    Anti-coagulant

Curacle’s SOLVADYS® Strategy

Curacle’s SOLVADYS® Strategy

CURACLE’S Approach

“SPAR: Phenotype-Based Approach & Structure-Phenotypic Activity Relationship”

Conventional Approach
Target-based Approach
  • [Follower or Best-in-class]
  • [SAR]
  • Defined molecular target
  • Target-based assay: biochemical & biophysical
  • Dependent on molecular docking
  • Favorable
  • Tolerable
  • Intolerable
Our Approach
Phenotype-based Approach
  • [First-in-class]
  • [SPAR]
  • No specific molecular target, Incompletely
    understood disease
  • Key Features of Disease
  • Distinctive assay portfolio
  • Phenotypic assay, cell-based assay
  • Empirical and model-based

Establishment of SPAR

CU06 Development as the first endothelial dysfunction blocker

  • CU06-1004, a small molecule endothelial dysfunction blocker developed by SOLVADYS
  • High correlation between structure and phenotype activity
  • New therapeutic concept for neurovascular and inflammatory diseases
Human
primary
endothelial
cells

Sequential
phenotype-based
screening

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연속적 표현형 기반 스크리닝
  • Anti-vascular leakage
    Inhibitory activity for stress
    fiber formation &
    VE-cadherin internalization
    Anti-hyperpermeability
    *FITC
    :Dextran Transwell assay&TEER
  • Multi-targeting
    & In vivo activity
    Assays for various
    endothelial activators
    Evaluation of efficacy in
    animal models
  • Anti-apoptosis
    (protection of ECs)
    Serum deprivation
    Hypoxia/reperfusion
  • Anti-inflammation
    Inhibition of NF-kB
    Suppression of ICAM-1
    & VCAM-1 expression
    Inhibition of leukocyte
    adhesion on ECs
  • CU06
    The first endothelial dysfunction blocker
  • Alleviate
    Degeneration of capillary
    vessels
    Endothelial barrier disruption
    Inflammatory activation
    Maintain
    Vascular density
    Endothelial
    functionality
    Improve
    Blood perfusion in tissues
  • Against acting on multiple endothelial activators
    VEGF, Ang-2, TNF-α, IL-1β, etc.