Papers by Dr Rajesh Rengasamy
Cancer Research, Aug 26, 2022
The authors subsequently decided not to disclose the complete structure (2) and requested to have... more The authors subsequently decided not to disclose the complete structure (2) and requested to have the article retracted. The authors apologize to the scientific community and deeply regret any inconveniences or challenges resulting from the publication and subsequent retraction of this article.
Cancer Research, Aug 25, 2022
Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was ini... more Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC. Significance: OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.
Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011... more Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer
Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–01... more Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer
Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was ini... more Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC.Significance:OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.
Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–01... more Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer
Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was ini... more Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/...
Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011... more Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer
Cancer Research, Aug 25, 2022
Cancer Research
The authors subsequently decided not to disclose the complete structure (2) and requested to have... more The authors subsequently decided not to disclose the complete structure (2) and requested to have the article retracted. The authors apologize to the scientific community and deeply regret any inconveniences or challenges resulting from the publication and subsequent retraction of this article.
Cancer Research
Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was ini... more Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/...
Journal of Life Science, 2009
Glycosidase inhibitors are major targets in the treatment of type Ⅱ diabetes, cancer and viral in... more Glycosidase inhibitors are major targets in the treatment of type Ⅱ diabetes, cancer and viral infections. This study was carried out to investigate the glycosidase inhibitory substances from bamboo (Phyllostachys bambusoides). Bamboo was extracted with methanol and then further fractionated with n-hexane, chloroform, n-BuOH and aqueous to get an active fraction. All extracts were evaluated for α-glucosidase inhibitory activities to identify the n-hexane fraction with 33.5 µg/ml of IC50 value. Active compound 1 in the n-hexane fraction was identified as linoleic acid, which exhibited inhibitory activity with 12.4 µM of IC50 value. Mechanistic analysis showed that linoleic acid exhibited noncompective inhibition. This is the first study in which bamboo is reported to show α-glucosidase inhibitory activity.
Journal of the Korean Society for Applied Biological Chemistry, 2011
Azasugars derived from L-alanine and L-serine were screened for inhibitory activity against αrham... more Azasugars derived from L-alanine and L-serine were screened for inhibitory activity against αrhamnosidase. The enantiomers of 1,6-dideoxynojirimycin (ent-1,6-dDNJ) (1) and (2S,3R)-2-(hydroxymethyl)piperidin-3-ol (5) showed highly specific and potent inhibition against αrhamnosidase with K i values of 4.2 and 16.6 μM, respectively. Structure of the best inhibitor features the same stereochemical configuration as L-rhamnose at C2, C3, and C4 centers. In kinetic studies, both compounds exhibited competitive inhibition behavior. Compound 1 manifested simple reversible slow-binding inhibition with the following kinetic parameters: k 3 = 1.17 nM −1 min −1 , k 4 = 5.96 ×10 −3 min −1 , and K i app =5.1 mM.
ChemInform, 2009
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Tetrahedron Letters, 2006
Quinoline derivatives R 0410 Synthesis of Quinaldines and Lepidines by a Doebner-Miller Reaction ... more Quinoline derivatives R 0410 Synthesis of Quinaldines and Lepidines by a Doebner-Miller Reaction under Thermal and Microwave Irradiation Conditions Using Phosphotungstic Acid.-A simple and general method for the synthesis of quinaldines and lepidines is developed. The reaction proceeds in the presence of tungstophosphoric acid under both conventional and microwave heating.-(SIVAPRASAD, G.
The Journal of Organic Chemistry, 2008
All NMR spectra were obtained on a 300 MHz spectrometer. 2D experiments NOSEY and COSY were used ... more All NMR spectra were obtained on a 300 MHz spectrometer. 2D experiments NOSEY and COSY were used to assist analysis of 1D spectra obtained on a 500 MHz spectrometer. All NMR experiments were run using standard routines. Flash column chromatography was performed using pre-packed silica gel columns. Thin layer chromatography was performed on commercially available glass-backed silica gel plates. Optical Rotations were measured using the Na-D line. All starting materials were dried in a vacuum for one day before use. All non-aqueous reactions were carried out under inert N 2 atmosphere, and reaction solvents were distilled according to standard procedures unless stated otherwise.
Bioorganic & Medicinal Chemistry, 2009
Six 1,3-diphenylpropanes exhibiting inhibitory activities against both the monophenolase and diph... more Six 1,3-diphenylpropanes exhibiting inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase were isolated from the methanol (95%) extract of Broussonetia kazinoki. These compounds, 1-6, were identified as kazinol C (1), D (2), F (3), broussonin C (4), kazinol S (5) and kazinol T (6). The latter two species (5 and 6) emerged to be new 1,3-diphenylpropanes which we fully spectroscopically characterized. The IC(50) values of compounds (1, 3-5) for monophenolase inhibition were determined to range between 0.43 and 17.9 microM. Compounds 1 and 3-5 also inhibited diphenolase significantly with IC(50) values of 22.8, 1.7, 0.57, and 26.9 microM, respectively. All four active tyrosinase inhibitors (1, 3-5) were competitive inhibitors. Interestigly they all mainfested simple reversible slow-binding inhibition against diphenolase. The most potent inhibitor, compound 4 diplayed the following kinetic parameters k(3)=0.0993 microM(-1)min(-1), k(4)=0.0048 min(-1), and K(i)(app)=0.0485 microM.
Journal of Sulfur Chemistry, 2015
A study involving scope in the condensation reaction of phenylsulfonylacetic acid with a series o... more A study involving scope in the condensation reaction of phenylsulfonylacetic acid with a series of carbonyl derivatives has been conducted. Reactivity trends favor formation of the corresponding vinyl sulfones when working with aryl aldehydes. Electron-deficient aryl aldehydes outperform electron-rich aryl aldehydes. Negligible differences were noted when using electron-rich and electron-deficient arylsulfonylacetic acid derivatives. Post-run analyses of the reaction mixture reveal formation of a minor product which resulted from methylidene transfer onto the carbonyl derivative. Support of a Knoevenagel-type condensation followed by decarboxylation is provided. GRAPHICAL ABSTRACT
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Papers by Dr Rajesh Rengasamy