Yissum - Research Development Company of the Hebrew University

Novel Indoline Derivatives as Anti-Inflammatory Agents for the Treatment of Diabetes

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

Novel Indoline Derivatives as Anti-Inflammatory Agents for the Treatment of Diabetes
Project ID : 7-2015-3171

Description of the technology


Small molecules, anti-inflammatory treatment

Development Stage

In-vivo proof of concept

Patent Status

Patent application filed


Inflammation indications: acute pancreatitis, acute live damage, fatty liver damage, diabetic nephropathy


  • Chronic activation of the immune system occurs in a variety of pathological conditions and is associated with the release of pro-inflammatory cytokines, TNF-a, IL-6, IL-1β and an increase in reactive oxygen species (ROS). Although TNF-a antagonists may produce a marked improvement in conditions such as rheumatoid arthritis and ulcerative colitis, they can also cause serious adverse effects.

Our Innovation

We have developed a family of indoline derivatives which prevent cytotoxicity induced by ROS and the release of pro-inflammatory cytokines from lipopolysaccharide (LPS) activated macrophages.

Pre-Clinical Results:

  • Acute pancreatitis – In a mouse model, 2 mg/kg of the compounds bring about almost complete prevention of rise in serum amylase and TNF-α, reduction by >50% of edema, necrosis and neutrophil infiltration and degradation of IκB-α in the pancreas after 4 h.
  • Acute liver damage - In a mouse model of acute liver damage, a dose of 0.25 mg/kg of the compounds brings about a >60% reduction of the increase in serum ALT and liver apoptosis, and reduction from 90% to 20% in the lethality in mice after 72 hr.
  • Fatty liver damage – In a fatty liver in-vivo model, 1 mg/kg/day causes significant reduction of the liver/body weight ratio, p<0.01, plasma ALT and liver fat content (oil red).
  • Diabetic Nephropathy – In a mouse model of type 1 diabetes, treatment with 0.25 mg/kg bid for 3 months abolishes the damage to the glomerular area and mesangial expansion. One of the compounds decreases the rise in serum and urine glucose, and urine urea (p<0.01), while another one reduces the albumin/creatinine ratio (p<0.01). Both compounds abolish the rise in gene expression of collagen 1 and 3, lipocalin 2 and fibronectin in the kidney. One compound also prevents the rise in TIMP1 and TGFβ

Key Features

  • Some of the compounds are also active through the oral route at about 2-5 times higher doses.
  • No adverse effects were seen during a 3-day observation period in mice after the injection of three of the compounds at doses of 25 mg/kg.
  • The compounds, which are readily prepared from commercially available compounds, are achiral. They are isolated as water soluble, crystalline salts.
  • The compounds are stable for extended periods, both in solid form as well as in aqueous solution.
  • These compounds and their biological activities have been patented.

Development Milestones

  • Seeking investment in new company or industrial collaboration for product development and clinical studies.

Researcher Information
Prof. Marta Weinstock,
Institute for Drug Research, The School of Pharmacy – Institute for Drug Research, Jerusalem, Israel

Prof. Abraham Nudelman,Chemistry Department, Bar Ilan University, Ramat Gan, Israel.

Project manager

Mel Larrosa
VP Business Development Healthcare

Project researchers

Marta Weinstock-Rosin
HUJI, School of Medicine - IMRIC
School of Pharmacy- Institute for Drug Research

Abraham Nudelman

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About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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