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Literature DB >> 31749911

Impact of Minor Structural Modifications on Properties of a Series of mTOR Inhibitors.

Gilles Ouvry¹, Laurence Clary¹, Loïc Tomas¹, Michèle Aurelly¹, Laetitia Bonnary¹, Emilie Borde¹, Claire Bouix-Peter¹, Laurent Chantalat¹, Claire Defoin-Platel¹, Sophie Deret¹, Mathieu Forissier¹, Craig S Harris¹, Tatiana Isabet², Laurent Lamy¹, Anne-Pascale Luzy¹, Jonathan Pascau¹, Catherine Soulet¹, Alessandro Taddei¹, Nathalie Taquet¹, Etienne Thoreau¹, Emeric Varvier¹, Emmanuel Vial¹, Laurent F Hennequin¹.

Abstract

Minor structural modifications-sometimes single atom changes-can have a dramatic impact on the properties of compounds. This is illustrated here on structures related to known mTOR inhibitor Sapanisertib. Subtle changes in the hinge binder lead to strikingly different overall profiles with changes in physical properties, metabolism, and kinase selectivity.

Entities: Gene

Year: 2019 PMID： 31749911 PMCID： PMC6862343 DOI： 10.1021/acsmedchemlett.9b00401

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

26 in total

Review 1. The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor.

Authors: Elisabeth Perzborn; Susanne Roehrig; Alexander Straub; Dagmar Kubitza; Frank Misselwitz
Journal: Nat Rev Drug Discov Date: 2010-12-17 Impact factor: 84.694

2. Cl-pi interactions in protein-ligand complexes.

Authors: Yumi N Imai; Yoshihisa Inoue; Isao Nakanishi; Kazuo Kitaura
Journal: Protein Sci Date: 2008-04-23 Impact factor: 6.725

3. 2,4,6-Triaminopyrimidine as a Novel Hinge Binder in a Series of PI3Kδ Selective Inhibitors.

Authors: Leena Patel; Jayaraman Chandrasekhar; Jerry Evarts; Aaron C Haran; Carmen Ip; Joshua A Kaplan; Musong Kim; David Koditek; Latesh Lad; Eve-Irene Lepist; Mary E McGrath; Nikolai Novikov; Stephane Perreault; Kamal D Puri; John R Somoza; Bart H Steiner; Kirk L Stevens; Joseph Therrien; Jennifer Treiberg; Armando G Villaseñor; Arthur Yeung; Gary Phillips
Journal: J Med Chem Date: 2016-03-29 Impact factor: 7.446

4. 4-methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.

Authors: Kevin K-C Liu; Shubha Bagrodia; Simon Bailey; Hengmiao Cheng; Hui Chen; Lisa Gao; Samantha Greasley; Jacqui E Hoffman; Qiyue Hu; Ted O Johnson; Dan Knighton; Zhengyu Liu; Matthew A Marx; Mitchell D Nambu; Sacha Ninkovic; Bernadette Pascual; Kristina Rafidi; Caroline M-L Rodgers; Graham L Smith; Shaoxian Sun; Haitao Wang; Anle Yang; Jing Yuan; Aihua Zou
Journal: Bioorg Med Chem Lett Date: 2010-08-14 Impact factor: 2.823

5. Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856.

Authors: Stephane Perreault; Jayaraman Chandrasekhar; Zhi-Hua Cui; Jerry Evarts; Jia Hao; Joshua A Kaplan; Adam Kashishian; Kathleen S Keegan; Thomas Kenney; David Koditek; Latesh Lad; Eve-Irene Lepist; Mary E McGrath; Leena Patel; Bart Phillips; Joseph Therrien; Jennifer Treiberg; Anella Yahiaoui; Gary Phillips
Journal: J Med Chem Date: 2017-02-07 Impact factor: 7.446

Review 6. Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target?

Authors: Tian Huang; Xiran Lin; Xianmin Meng; Mao Lin
Journal: Acta Derm Venereol Date: 2014-07 Impact factor: 4.437

7. Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet.

Authors: N F Agamia; D M Abdallah; O Sorour; B Mourad; D N Younan
Journal: Br J Dermatol Date: 2016-04-20 Impact factor: 9.302

Impact of Minor Structural Modifications on Properties of a Series of mTOR Inhibitors.

Review 1. The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor.

2. Cl-pi interactions in protein-ligand complexes.

3. 2,4,6-Triaminopyrimidine as a Novel Hinge Binder in a Series of PI3Kδ Selective Inhibitors.

4. 4-methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.

5. Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856.

Review 6. Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target?

7. Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet.

8. Combination of everolimus and tacrolimus: a potentially effective regimen for recalcitrant psoriasis.

9. mTOR kinase structure, mechanism and regulation.

10. mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target.

Review 1. Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold.