Case Number 098013 - Compounds to Treat Obesity
Contact: Jill Uhl
Description: Obesity is now considered as a global epidemic with over one billion people being overweight. About $33 billion is being spent each year in USA on weight reduction products. To date no satisfactory drug is available to control obesity. Therefore, millions of dollars are spent each year towards the development of new treatments to fight this epidemic.
Neuropeptide Y (NPY) is the most abundant peptide present in the mammalian brain. It has also been characterized as the most powerful orexigenic (stimulation of feeding) substance isolated to date. As described below, UC researcher, Ambikaipakan Balasubramaniam, has developed two groups of compounds based on NPY to control food intake, and are currently looking for partners for further development of these anti-obesity compounds.
Group 1 Compounds: It has recently been demonstrated that peripheral administration of PYY(3-36), a NPY Y2 receptor-preferring ligand, can reduce appetite and food intake in normal and fasted rodents, as well as in normal and obese humans (Nature 418:650-654; 2002, N Engl J Med 349:941-948; 2003). However, PYY(3-36) can also potently interact with other NPY receptors (Y4 & Y5), which excludes its use as an anti-obesity drug.
In this regard, we have developed highly selective and potent (Ki = 1 nM) Y2-receptor agonists based on PYY(22-36) sequence, and shown that they exhibit potent and prolong in vivo activities (J Med Chem 49:3420-3427; 2000; Dig Dis Sci. 44:643-648; 1999). In addition, we have also developed highly selective and potent (Ki = 1 nM) Y2 receptor agonists based on PYY(25-36), and determined they exhibit potent activities in in-vivo models. All these analogs based on PYY(22-36), PYY(25-36) and their deletion peptides have been patented (US Patents: 5,604,203 & 6,046,167). Moreover, selected PYY(22-36) & PYY(25-36) analogs have been determined to inhibit food intake in a mice model during peripheral administration 2, 4 or 24 h.
Group 2 Compounds: We have developed a series of lower molecular weight compounds (< 600) based on NPY, and have previously shown that these compounds could significantly attenuate the food intake in NPY-treated and fasted rats over 4-8 h during central administration. The composition and the use of these compounds have also been patented (US patents 6,013,633 & 6,235,718). Recently, we developed additional new compounds to facilitate entry into the brain, and have now determined that these compounds could significantly inhibit the food intake in rats over 8 h (bolus dose, ip). These compounds could therefore be developed into drugs to treat obesity.
The technology has the following advantages:
- Lower molecular weight compounds- will be economical to develop into drugs.
- Highly potent and selective- will be active at lower doses & little or no side effect expected.
- Compounds are active peripherally- Could be easily administered.
- Relatively stable- long acting.
The technology portfolio includes the following issued patents:
- 5,604,203 - Analogs of peptide YY and uses thereof
- 6,046,167 - Peptide YY analogs
- 6,013,633 - Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm
- 6,235,718 - Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm
- 6,737,408 - Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm
- 6,962,902 - Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm
- 7,465,710 - Compounds for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm
- 7,994,119 - Compounds for control of appetite