Montpellier, France
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Fauvel B.,OriBase Pharma | Yasri A.,OriBase Pharma
mAbs | Year: 2014

Approximately 30 therapeutic monoclonal antibodies have already been approved for cancers and inflammatory diseases, and monoclonal antibodies continue to be one of the fastest growing classes of therapeutic molecules. Because aberrant signaling by receptor tyrosine kinases (RTKs) is a commonly observed factor in cancer, most of the subclasses of RTKs are being extensively studied as potential targets for treating malignancies. The first two RTKs that have been targeted by antibody therapy, with five currently marketed antibodies, are the growth factor receptors EGFR and HER 2. However, due to systemic side effects, refractory patients and the development of drug resistance, these treatments are being challenged by emerging therapeutics. This review examines current monoclonal antibody therapies against RTKs. After an analysis of agents that have already been approved, we present an analysis of antibodies in clinical development that target RTKs. Finally, we highlight promising RTKs that are emerging as new oncological targets for antibody-based therapy. © 2014 Landes Bioscience.


Gaudin C.,Charles Gerhardt Institute | Gaudin C.,University of Versailles | Cunha D.,University of Versailles | Ivanoff E.,Charles Gerhardt Institute | And 6 more authors.
Microporous and Mesoporous Materials | Year: 2012

A series of 10 MIL-88B(Fe) iron(III) dicarboxylate MOFs wherein the organic linker is functionalized by a large variety of polar and apolar functional groups (-H, -Br, -F, -CF 3, -CH 3, -NH 2, -NO 2, -OH) was investigated as a potential carrier for encapsulating drugs, using the cosmetic amphiphilic caffeine as a model molecule. Encapsulation using impregnation followed by thermogravimetric analysis (TGA) and high performance liquid chromatography (HPLC) measurements to quantitatively estimate the caffeine uptake, have been first performed on the functionalized MIL-88B(Fe) samples. This set of experimental data was further used as an ideal platform to conduct a quantitative structure activity relationship approach based on multiple linear regression (MLR) method with the aim to find out the most relevant chemical and structural features of the MIL-88B(Fe) that significantly affect the therapeutic molecule uptake. Individual QSAR models showed that tuning the polarity and the H-donor capacity of the organic linker can enhance the caffeine encapsulation, suggesting that the functional groups serve as anchoring points for the drug molecule, consistent with previous conclusions drawn from molecular simulations performed on similar functionalized MOFs. Consensus modeling approach based on the selection of the most diverse individual models was also employed to build more representative QSAR models over the chemical space that could be further used to predict the drug encapsulation performance of the MOFs grafted by other functional groups. © 2011 Elsevier Inc. All rights reserved.


Feneyrolles C.,OriBase Pharma | Spenlinhauer A.,OriBase Pharma | Guiet L.,OriBase Pharma | Fauvel B.,OriBase Pharma | And 4 more authors.
Molecular Cancer Therapeutics | Year: 2014

Receptor tyrosine kinases (RTK) are transmembrane receptors that regulate signal transduction in cells. As a member of the TAM (Tyro-3, Axl, Mer) RTK subfamily, Axl regulates key processes such as cell growth, migration, aggregation, and apoptosis through several pathways. Its overexpression/overactivation has been underlined in several conditions, especially cancers, and in both chemotherapy and targeted therapy sensitivity loss. In this review, we propose to highlight the therapeutic implication of Axl, starting with the pathways it regulates, validating its interest as a therapeutic target, and defining the tools available to develop strategies for its inhibition. We especially focus on small molecule inhibitors, their structure, inhibition profile, and development stages. © 2014 AACR.


Lakhlili W.,Mohammed V University | Cheve G.,OriBase Pharma | Yasri A.,OriBase Pharma | Ibrahimi A.,Mohammed V University
OncoTargets and Therapy | Year: 2015

The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3Kγ, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site. © 2015, 2015 Lakhlili et al.


Patent
French Institute of Health, Medical Research, Institute Regional Du Cancer Of Montpellier Val Daurelle, Montpellier University and Oribase Pharma | Date: 2012-06-22

The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9 and SEQ ID NO: 10.


Patent
Oribase Pharma | Date: 2013-12-30

The present invention relates to compounds of the following formula (I) and/or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.


Patent
Oribase Pharma | Date: 2013-12-30

The present invention relates to compounds of the following formula (I) and/or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.


Patent
Oribase Pharma | Date: 2013-12-30

The present invention relates to compounds of the following formula (I) and/or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.


Patent
Oribase Pharma, Institute Regional Du Cancer Of Montpellier Val D Aurelle, French Institute of Health, Medical Research and Montpellier University | Date: 2012-06-22

The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9, SEQ ID NO: 10 and SEQ ID NO: 11.


PubMed | Mohammed V University and OriBase Pharma
Type: | Journal: OncoTargets and therapy | Year: 2015

The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3K, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site.

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