Synthesis and in vivo SAR study of indolin-2-one-based multi-targeted inhibitors as potential anticancer agents
Long Zhang1, Qingmei Zheng1, Yingying Yang1
1Shandong Provincial Key Laboratory of Small Molecular Targeted drugs, Qilu Pharmaceutical Co, Ltd, 243 Gong Ye Bei Road, Jinan 250100, Shandong Province, PR China.
Abstract:
A series of indolin-2-one analogues were designed and synthesized, and all of them exhibited excellent in vitro potency. The structure and in vivo activity or toxicity relationship (in-vivo SAR) investigation of indolin-2-one structural analogues was carried out. In vivo efficacy studies indicated that 3b significantly suppressed tumor growth in HT-29 and NCI-H460 xenografts without causing significant loss of body weight. Kinase assay showed that compound 3b effectively inhibited the VEGFR-2, VEGFR-3, FLT3, Ret and PDGFR-β kinases, but had little effect on the VEGFR-1 kinase. Besides, 3b showed higher selectivity for VEGFR-2 compared with PDGFR-β. On the basis of its selectivity and safety properties, 3b was identified as a drug candidate for the treatment of cancer.
More Related Videos
Related Concept Videos
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Inhibition of Cdk Activity
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...


