CLT-005

CLT-005 is a small molecule compound with potent anti-inflammatory and anti-angiogenic activity. CLT-005 inhibits modulations in cellular transcription that occur in response to inflammatory or angiogenic factors.


 

Rationale for Stat3 as a Target

•Activated Stat3 found in Choroidal Neovascular membranes of patients with AMD
•Elevated levels of Stat3 activator cytokines (IL-6, Leptin, VEGF) detected clinically in the vitreous of patients with AMD, DR, and DME
•Progression of Dry AMD correlates with increased serum levels of IL-6
–Followed patients for an average of 4.6 years
•CNV is inhibited by IL-6 or Jak2 inhibition in animal models
•NADPH Oxidase activates Stat3 in the diabetic retina
–Effective pharmacologic treatments inhibit Stat3 activation

 

Intravitreal delivery of VEGF causes rapid activation of Stat3 in mice

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CLT-005 prevents Stat3 nuclear translocation in HUVEC cells

CLT-005 prevents Stat3 nuclear translocation in HUVEC cells

CLT-005 reduces expression of inflammatory and angiogenic molecules

•WT or STZ-rats
•Intravitreal injection of 50 ng or 5 µg CLT-005 in DMSO
•Retina/RPE harvested at 24 hr for qRT-PCR

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LRP-6IL-6ICAM-1

CLT-005 REDUCES EXPRESSION LEVELS OF SEVERAL INFLAMMATORY AND

CLT-005 reduces retinal vascular permeability in STZ-rats

•STZ-rats
•Bilateral Intravitreal injection
•Evans Blue Extravasation
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•STZ-rats
•OS:  Intravitreal Vehicle
OD:  Intravitreal CLT-005 (5 μg)
•Immunoblot on Retina
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Ophthalmic Contract Research