Aliskiren (Tekturna) is the first orally active renin inhibitor approved for clinical use. It was approved by the US Food and Drug Administration and the European Medicines Agency in 2007 for the treatment of Primary hypertension. It was developed by Ciba-Geigy (now Novartis).

1. DISCOVERY OF ALISKIREN
SAKEEL AHMED (PhD Scholar)
Department of Pharmacology (NIPER, Mohali)

2. ALISKIREN
 Aliskiren (Tekturna) is the first orally active renin inhibitor approved for clinical use.
 It was approved by the US Food and Drug Administration and the European Medicines
Agency in 2007 for the treatment of Primary hypertension.
 Aliskiren has shown efficacy as a monotherapy.
 Combining Aliskiren with other antihypertensive drugs, ACE inhibitors, ARBs, calcium-
channel blockers and diuretics
 It was developed by Ciba-Geigy (now Novartis).
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3. RENIN ANGIOTENSIN SYSTEM
(Matthew J. Munro et al., 2017) 3

4. CLASSIFICATION OF RENIN INHIBITORS
1. First Generation:
Example: Enalikiren (CGP29287)
2. Second Generation:
Example: CGP38560 3. Third Generation:
Example: Aliskiren
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5. The peptidomimetic approach was unsuccessful.
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6. COMPUTATIONAL APPROACH FOR ALISKIREN
Figure: 3D model of the enzyme and docking of
CGP38560.
Figure: The predicted bioactive conformation of
CGP38560.
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7. The drug design strategy based on the predicted bioactive conformation of CGP38560
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8. 8

9. Four compounds representing a third generation of
renin inhibitors: the THQ, phenoxy, indole and
salicylamide leads
From μM to nM biological activities in the phenoxy series.
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10. Figure: Superimposition of the four lead compounds
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11. Figure: The complex with Aliskiren and the S3sp sub-
pocket
Figure: Comparison between the predicted bioactive conformation
of CGP38560 (red) and the one observed experimentally (black)
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12. Aliskiren
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14. The Renin Project in perspective.
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15. REFERENCES
1. Cohen, N. C. and Park, T. (2007) ‘Structure-Based Drug Design and the Discovery of
Aliskiren ( Tekturna Ò ): Perseverance and Creativity to Overcome a R & D Pipeline
Challenge ‡’, pp. 557–565. doi: 10.1111/j.1747-0285.2007.00599.x.
2. Imanishi, T., Tsujioka, H. and Akasaka, T. (2009) ‘Hypertension Management and End Organ
Protection : Focus on Aliskiren’, pp. 321–331.
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