Presentations & Publications
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Products
Tolinapant (ASTX660) – T-cell Lymphomas
2024
- Martins et al; “The preclinical pharmacokinetics of Tolinapant—A dual cIAP1/XIAP antagonist with in vivo efficacy” Pharmacol Res Perspect, 2024
- Ward, et al; “Epigenetic priming by hypomethylation enhances the immunogenic potential of tolinapant in T-cell lymphoma”; Cancer Research Communications, 2024
2023
- 2023 ASH (poster): Epigenetic priming by hypomethylation enhances the immunogenic potential of tolinapant in T-cell lymphoma
- Shibuya, et al. “SMAC Mimetics Synergistically Cooperate with HDAC Inhibitors Enhancing TNF-α Autocrine Signaling”; Cancers 2023
2022
- 2022 ACoP: A Population Pharmacokinetic Model of Tolinapant in Subjects with Advanced Solid Tumors and Lymphomas
- 2022 TCLF – Encore Presentation: Preliminary Analysis of the Phase II Study Suing Tolinapant (ASTX6660) Monotherapy in 98 Peripheral T-Cell Lymphoma and 51 Cutaneous T-Cell Lymphoma Subjects with Relapsed Refractory Disease
- 2022 TCLF: Trials-In-Progress, A Phase 1-2, Open-Label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Activity of Tolinapant in Combination with Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects with Relapsed/Refractory Peripheral T-cell Lymphoma
- 2022 EHA: Preliminary Analysis of the Phase II Study Suing Tolinapant (ASTX6660) Monotherapy in 98 Peripheral T-Cell Lymphoma and 51 Cutaneous T-Cell Lymphoma Subjects with Relapsed Refractory Disease
- 2022 EHA: COMBINING THE IAP ANTAGONIST, TOLINAPANT, WITH A DNA HYPOMETHYLATING AGENT ENHANCES ANTI-TUMOUR MECHANISMS IN PRECLINICAL MODELS OF T-CELL LYMPHOMA
2021
- 2021 ASH: Combining the IAP Antagonist Tolinapant with a DNA Hypomethylating Agent Enhances Immunogenic Cell Death in Preclinical Models of T-Cell Lymphoma
- Ferrari, et al. “Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma”, 2021
2020
- 2020 EORTC-NCI-AACR: The non-peptidomimetic cIAP1/2 and XIAP antagonist tolinapant promotes an anti-tumour immune response in T-cell lymphoma
- 2020 AACR: ASTX660, a non-peptidomimetic antagonist of cIAP1/2 and XIAP, promotes an anti-tumor immune response in pre-clinical models of T-cell lymphoma
- 2020 EHA: Characterization of ASTX660, an antagonist of cIAP1/2 and XIAP, in mouse models of T cell lymphoma
- Ye, et al. “ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer”
- Mita, et al. “A Phase 1 Study of ASTX660, an Antagonist of Inhibitors of Apoptosis Proteins, in Adults With Advanced Cancers or Lymphoma”
- Dittmann, et al. “Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways”
2019
- 2019 EORTC: Preliminary results of ASTX660, a novel non-peptidomimetic cIAP1/2 and XIAP antagonist, in 118 patients with solid tumors or lymphoma
- Xiao, et al. “Dual Antagonist of cIAP/XIAP ASTX660 Sensitizes HPV−and HPV+ Head and Neck Cancers to TNFα, TRAIL, and Radiation Therapy”
- 2019 EHA: ASTX660, a non-peptidomimetic antagonist of cIAP1/2 and XIAP, induces apoptosis in T cell lymphoma by enhancing immune mediated and death receptor dependent killing
- 2019 EHA: Preliminary Results of ASTX660, a Novel Non-Peptidomimetic cIAP1/2 and XIAP Antagonist, in Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma
More publications are viewable in the archive.
Beroterkib (ASTX029) – Solid Tumors
2024
2022
- ENA Poster (2022): A combination vertical inhibition approach with inhibitors of SHP2 and ERK provides improved activity in KRAS-mutant pancreatic and colorectal cancer models
- 2022 ASCO: A First-in-Human, Phase 1 Study of ASTX029, a Dual-Mechanism Inhibitor of ERK1/2, in Relapsed/Refractory Solid Tumors
2021
- 2021 EORTC: Treatment with the dual mechanism ERK inhibitor, ASTX029, alters myeloid cell differentiation
- Heightman et al., “Discovery of ASTX029, A Clinical Candidate Which Modulates the Phosphorylation and Catalytic Activity of ERK1/2”
- Munck et al., “ASTX029, a Novel Dual-Mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK”
- 2021 AACR: A first-in-human, Phase 1 study of ASTX029, a dual-mechanism inhibitor of ERK1/2, in relapsed/refractory solid tumors
- 2021 AACR: Immune modulation by the dual-mechanism ERK inhibitor, ASTX029, in MAPK-activated tumor models
2020
- 2020 ASH: Anti-tumor Activity of ASTX029, a Dual Mechanism Inhibitor of ERK1/2, in Preclinical AML Models
- Combined inhibition of SHP2 and ERK enhances anti-tumor effects in preclinical models
- The clinical candidate, ASTX029, is a novel, dual mechanism ERK1/2 Inhibitor and has potent activity in MAPK-activated cancer cell lines and in vivo tumor models
- Kidger et al., “Dual-mechanism ERK1/2 inhibitors exploit a distinct binding mode to block phosphorylation and nuclear accumulation of ERK1/2”; Mol Cancer Ther, 2020
2019
ASTX295 – Solid Tumors
2024
- 2024 ENA (poster): Pulsatile Induction of the p53 Pathway by MDM2 Antagonist ASTX295 Shows an Enhanced Therapeutic Index in vivo
- 2024 ENA (poster): Identification of Biomarkers Predictive of Response to ASTX295, a Next-Generation MDM2 Antagonist, in Solid Tumors Carrying Wild-type p53
- 2024 AACR (oral): Discovery of ASTX295, a potent, next-generation small molecule antagonist of MDM2 with differentiated pharmacokinetic profile. From concept to clinic.
- 2024 AACR (poster): Identification of biomarkers of response to MDM2 inhibition in solid tumours using computational, multi-omics approaches.
- 2024 AACR (poster): Phase 1 study of MDM2 antagonist ASTX295 in patients with solid tumors with wild-type TP53
- 2024 AACR (poster): Targeting the MDM2-p53 interaction: Time-and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index
2022
2021
2020
2019
Discovery Science
Publications
2024
- Martins et al; “The preclinical pharmacokinetics of Tolinapant—A dual cIAP1/XIAP antagonist with in vivo efficacy” Pharmacol Res Perspect, 2024 https://doi.org/10.1002/prp2.70030
- Ramos et al; “Proteome-wide CETSA reveals diverse apoptosis-inducing mechanisms converging on an initial apoptosis effector stage at the nuclear periphery” Cell Reports, 2024 https://doi.org/10.1016/j.celrep.2024.114784
- Palmer et al; “Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of β-Glucocerebrosidase” J Med Chem, 2024 https://doi.org/10.1021/acs.jmedchem.4c00702
- Gustavvson et al; “The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1” Science Advances, 2024 https://www.science.org/doi/10.1126/sciadv.adk1296?
- Ma et al; “Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRASG12C Inhibitor” J. Med. Chem. 2024 https://doi.org/10.1021/acs.jmedchem.4c00572
- Mukherjee, et al; “Protein engineering enables a soakable crystal form of human CDK7 primed for high-throughput crystallography and structure-based drug design”; Structure. 2024 https://doi.org/10.1016/j.str.2024.05.011
- Sanchez-Garcia et al; “CESPED: A benchmark for supervised particle pose estimation in cryo-EM” Physical Review Research. 2024 https://doi.org/10.1103/PhysRevResearch.6.023245
- Ward, et al; “Epigenetic priming by hypomethylation enhances the immunogenic potential of tolinapant in T-cell lymphoma”; Cancer Research Communications, 2024 https://doi.org/10.1158/2767-9764.CRC-23-0415
- Dean et al; “Alkene 1,3-Difluorination via Transient Oxonium Intermediates” Angewandte Chemie. 2024 https://doi.org/10.1002/anie.202404666
- Henderikx et al., “VitroJet: new features and case studies”; Structural Biology. 2024 https://journals.iucr.org/d/issues/2024/04/00/ih5005/index.html
- Day et al., “Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2)”; J. Med. Chem. 2024 https://doi.org/10.1021/acs.jmedchem.3c02118
- Woodhead et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2022”; J. Med. Chem. 2024 https://doi.org/10.1021/acs.jmedchem.3c02070
2023
- Townley et al., “Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist’s toolbox reactions”; RSC Med. Chem.2023 https://doi.org/10.1039/D3MD00495C
- Wu et al., “A Diverse Array of Large Capsules Transform in Response to Stimuli”; J. Am. Chem. Soc. 2023 https://doi.org/10.1021/jacs.3c02491
- Morado et al., “Does a Machine-Learned Potential Perform Better Than an Optimally Tuned Traditional Force Field? A Case Study on Fluorohydrins”; J. Chem. Inf. Model. 2023 https://pubs.acs.org/doi/10.1021/acs.jcim.2c01510
- Taylor et al., “Accelerated Chemical Reaction Optimization using Multi-Task Learning”; ACS Cent. Sci. 2023 https://doi.org/10.1021/acscentsci.3c00050
- Taylor et al., “A Brief Introduction to Chemical Reaction Optimization”; Chem Rev. 2023 https://doi.org/10.1021/acs.chemrev.2c00798
- Wu et al., Systematic construction of progressively larger capsules from a fivefold linking pyrrole-based subcomponent. Nature Synthesis 2023 https://doi.org/10.1038/s44160-023-00276-9
- Walsh et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2021”; J Med Chem 2023 https://doi.org/10.1021/acs.jmedchem.2c01827
2022
- Rees et al., “Introduction to the themed collection on fragment-based drug discovery”; RSC Med. Chem 2022 https://doi.org/10.1039/D2MD90037H
- Martins et al., “A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies”; Xenobiotica 2022 https://doi.org/10.1080/00498254.2022.2130838
- Chan et al., “A multilevel generative framework with hierarchical self-contrasting for bias control and transparency in structure-based ligand design”; Nat. Mach. Intell. 2022 https://doi.org/10.1038/s42256-022-00564-7
- Jones et al., “Exploration of piperidine 3D fragment chemical space: synthesis and 3D shape analysis of fragments derived from 20 regio- and diastereoisomers of methyl substituted pipecolinates”; RSC Medicinal Chemistry, Oct 2022 https://doi.org/10.1039/D2MD00239F
- Blunt et al., “Perspective on the Current State-of-the-Art of Quantum Computing for Drug Discovery Applications”; J Chem Theory Comput 2022 https://doi.org/10.1021/acs.jctc.2c00574
- Lea et al., “Cryo-EM diversifies”; Current Opinion in Structural Biology 2022 https://doi.org/10.1016/j.sbi.2022.102469
- St. Denis et al., “X-ray Screening of an Electrophilic Fragment Library and Application toward the Development of a Novel ERK 1/2 Covalent Inhibitor”; J. Med. Chem. 2022 https://doi.org/10.1021/acs.jmedchem.2c01044
- Tamanini et al., “Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor”; ACS Med. Chem. Lett. 2022 https://doi.org/10.1021/acsmedchemlett.2c00272
- da Silva Júnior et al., “Growth vector elaboration of fragments: regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine”; Org. Biomol. Chem. 2022 https://doi.org/10.1039/D2OB00968D
- Priyanka et al., “Mitoxantrone stacking does not define the active or inactive state of USP15 catalytic domain”; J. Struct. Biol. 2022 https://doi.org/10.1016/j.jsb.2022.107862
- Izsák et al., “Quantum computing in pharma: A multilayer embedding approach for near future applications”; J. Comput. Chem. 2022 https://doi.org/10.1002/jcc.26958
- Martins et al., “A validated liquid chromatography-tandem mass spectroscopy method for the quantification of tolinapant in human plasma”; Anal. Sci. Adv. 2022 https://doi.org/10.1002/ansa.202200009
- Kakade et al., “Mapping of a N-terminal α-helix domain required for human PINK1 stabilization, Serine228 autophosphorylation and activation in cells”; Open Biol .2022 https://doi.org/10.1098%2Frsob.210264
- Pomberger et al., “The effect of chemical representation on active machine learning towards closed-loop optimization”; React. Chem. Eng. 2022 https://doi.org/10.1039/D2RE00008C
- Poelking et al., “BenchML: an extensible pipelining framework for benchmarking representations of materials and molecules at scale”; Mach. Learn.: Sci. Technol. 2022 https://doi.org/10.1088/2632-2153/ac4d11
- Cons et al., “Electrostatic Complementarity in Structure-Based Drug Design”; J. Med. Chem. 2022 https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c00164
- Poelking et al., “Meaningful machine learning models and machine-learned pharmacophores from fragment screening campaigns”; arXiv 2022 https://doi.org/10.48550/arXiv.2204.06348
- de Esch et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2020”; J. Med. Chem. 2022 https://doi.org/10.1021/acs.jmedchem.1c01803
- Rees., “Medicines for millions of patients”; RSC Medicinal Chemistry, Jan 2022 https://doi.org/10.1039/D1MD00279A
2021
- Norton et al., “Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein−Protein Interaction”; J. Med. Chem. 2021 https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01351
- Chessari et al., “C–H functionalisation tolerant to polar groups could transform fragment-based drug discovery (FBDD)”; Chemical Science, 2021 https://doi.org/10.1039/D1SC03563K View software
- Almeida et al., “NMR Reporter Assays for the Quantification of Weak-Affinity Receptor–Ligand Interactions”; SLAS Discovery, April 2021 https://doi.org/10.1177/24725552211009782
- Poon et al., “The role of SQSTM1 (p62) in mitochondrial function and clearance in human cortical neurons”; Stem Cell Reports 2021 https://doi.org/10.1016/j.stemcr.2021.03.030
- Chessari at al. Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein–Protein Interaction; Med Chem 2021 https://doi.org/10.1021/acs.jmedchem.0c02188
- Sethi et al., “Leveraging omic features with F3UTER enables identification of unannotated 3’UTRs for synaptic genes” https://www.nature.com/articles/s41467-022-30017-z View software
- Brain et al., “The Discovery of Kisqali® (Ribociclib): A CDK4/6 Inhibitor for the Treatment of HR+/HER2− Advanced Breast Cancer”; Successful Drug Discovery; Vol 5; 2021; chapter 9 https://doi.org/10.1002/9783527826872.ch9
- Grainger et al., “A Perspective on the Analytical Challenges Encountered in High-Throughput Experimentation”; Organic Process Research and Development, 2021 https://dx.doi.org/10.1021/acs.oprd.0c00463
- St. Denis et al., “Fragment-based drug discovery: opportunities for organic synthesis”; RSC Medicinal Chemistry, 2021 https://pubs.rsc.org/en/content/articlelanding/2021/md/d0md00375a#!divAbstract
2020
- Holvey et al., “Identifying and Developing Small Molecule Inhibitors of Protein–Protein Interactions”; RSC Publications, 2020 https://doi.org/10.1039/9781839160677
- Jahnke et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2019”; Journal of Medicinal Chemistry, 2020 https://doi.org/10.1021/acs.jmedchem.0c01608
- Cadilla et al., “The exploration of aza-quinolines as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors with low brain exposure”; Bioorganic & Medicinal Chemistry, 2020 https://doi.org/10.1016/j.bmc.2020.115791
- Downes et al., “Design and Synthesis of 56 Shape-Diverse 3D Fragments”; Chemistry: A European Journal, 2020 https://chemistry-europe.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/chem.202001123
- Erlanson et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2018”; Journal of Medicinal Chemistry, 2020 https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01581
- Coyle et al., “Applied Biophysical Methods in Fragment-Based Drug Discovery”; SLAS DISCOVERY, 2020 https://journals.sagepub.com/doi/full/10.1177/2472555220916168
- Saur et al. “Fragment-based drug discovery using cryo-EM”, Drug Discovery Today, 2020 https://www.sciencedirect.com/science/article/pii/S1359644619304659?viewFullText=true
- Kidger et al., “Dual-mechanism ERK1/2 inhibitors exploit a distinct binding mode to block phosphorylation and nuclear accumulation of ERK1/2”; Mol Cancer Ther, 2020 https://doi.org/10.1158/1535-7163.mct-19-0505
- Osbourne et al., “Fragments: where are we now?”; Biochemical Society Transactions, 2020 https://portlandpress.com/biochemsoctrans/article-abstract/48/1/271/221949/Fragments-where-are-we-now
- Rathi et al., “Practical High-Quality Electrostatic Potential Surfaces for Drug Discovery Using a Graph-Convolutional Deep Neural Network”; Journal of Medicinal Chemistry, 2020 https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.9b01129 View modeling software
2019
- Mortenson et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2017”, Journal of Medicinal Chemistry, 2019 https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.8b01472
- Murray et al., “A successful collaboration between academia, biotech and pharma led to discovery of erdafitinib, a selective FGFR inhibitor recently approved by the FDA”; MedChemComm, 2019 https://pubs.rsc.org/en/content/articlepdf/2019/MD/C9MD90044F
- Heightman et al., “Structure–Activity and Structure–Conformation Relationships of Aryl Propionic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1/Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1/NRF2) Protein–Protein Interaction.” J. Med. Chem., 2019 DOI: 10.1021/acs.jmedchem.9b00279
- Deaton et al., “The discovery of quinoline-3-carboxamides as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors.” Bioorganic & Medicinal Chemistry, 2019 doi.org/10.1016/j.bmc.2019.02.017
- O’Reilly et al., “Crystallographic screening using ultra-low-molecular-weight ligands to guide drug design.” Drug Discovery Today, 2019 doi.org/10.1016/j.drudis.2019.03.009
- Ceska et al., “Cryo-EM in drug discovery” Biochemical Society Transactions (2019) 10.1042/BST20180267
- Grainger et al., “Enabling Synthesis in Fragment-Based Drug Discovery by Reactivity Mapping: Photoredox-Mediated Cross-Dehydrogenative Heteroarylation of Cyclic Amines.” Chemical Science 2019 10.1039/C8SC04789H
2018
- Šuštić et al., “A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers”; Genome Med. 2018 https://doi.org/10.1186/s13073-018-0600-z
- Lebraud., et al., “Quantitation of ERK1/2 inhibitor cellular target occupancies with a reversible slow off-rate probe.” Chem. Sci. October 2018, Issue 37 Doi.org/10.1039/c8sc02754d
- Jubb et al., “COSMIC-3D provides structural perspectives on cancer genetics for drug discovery.” Nature Genetics 2018 DOI: 10.1038/s41588-018-0214-9
- Johnson et al., “A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-b]pyridin-1-yl)-2-[(2R,5R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660).” J. Med. Chem., 2018 DOI: 10.1021/acs.jmedchem.8b00900
- Wright et al., “Engineering and purification of a thermostable, high-yield, variant of PfCRT, the Plasmodium falciparum chloroquine resistance transporter.” Protein Expression and Purification 141 (2018) 7-18; DOI: 10.1016/j.pep.2017.08.005 DOI: 10.1016/j.pep.2017.08.005
- Ward et al., “ASTX660, a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP, potently induces TNF-α dependent apoptosis in cancer cell lines and inhibits tumor growth.” Molecular Cancer Therapeutics 2018 pre-publication DOI: 10.1158/1535-7163.MCT-17-0848
- Johnson et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2016.” J. Med. Chem. 2018, 61, 1774−1784 DOI: 10.1021/acs.jmedchem.7b01298
- Lebraud et al., “A highly potent clickable probe for cellular imaging of MDM2 and assessing dynamic responses to MDM2-p53 inhibition.” Bioconjugate Chemistry 2018 (ahead of print) DOI: 10.1021/acs.bioconjchem.8b00315
- Heightman et al., “Fragment-Based Discovery of a Potent, Orally Bioavailable Inhibitor That Modulates the Phosphorylation and Catalytic Activity of ERK1/2.” J. Med. Chem. 2018 61, 11, 4978-4992 DOI: 10.1021/acs.jmedchem.8b00421
- Agni Gavriilidou et al., “Advancing Life Sciences R&D 2018 Online, Application of Native ESI-MS to Characterize Interactions between Compounds Derived from Fragment-Based Discovery Campaigns and Two Pharmaceutically Relevant Proteins.” SLAS Discovery DOI: 10.1177/2472555218775921
- Xue et al., “MAP3K1 and MAP2K4 mutations are associated with sensitivity to MEK inhibitors in multiple cancer models”; Cell Res. 2018 https://doi.org/10.1038/s41422-018-0044-4
- Rees et al. “Organic synthesis provides opportunities to transform drug discovery.” Nature Chemistry (vol 10) Apr 2018, 383-394 DOI: 10.1038/s41557-018-0021-z
2017
- Perera TPS, et al., “Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor.” Mol Cancer Ther, 2017, Vol 16, No. 6 pp. 1010– 1020 DOI: 10.1158/1535-7163.MCT-16-0589
- Sipthorp et al., ” Visualization of Endogenous ERK1/2 in Cells with a Bioorthogonal Covalent Probe.” Bioconjugate Chemistry, (JUN 2017) Vol. 28, No. 6, pp. 1677-1683 DOI: 10.1021/acs.bioconjchem.7b00152
- Lebraud et al., “Protein degradation: a validated therapeutic strategy with exciting prospects.” Essays in Biochemistry (2017) 61 517–527 DOI: 10.1042/EBC20170030
- Price et al., “Fragment-based drug discovery and its application to challenging drug targets.” Essays in Biochemistry (2017) 61 475–484 DOI: 10.1042/EBC20170029
- Hall et al., “The Fragment Network: A Chemistry Recommendation Engine Built Using a Graph Database.” J. Med. Chem., 2017, 60(14), pp 6440-6450 DOI: 10.1021/acs.jmedchem.7b00809
- Tamanini et al., “Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP).” J. Med. Chem., 2017, 60(11), pp 4611-4625 DOI: 10.1021/acs.jmedchem.6b01877
- Rathi et al., “Predicting ‘Hot’ and ‘Warm’ Spots for Fragment Binding.” J. Med. Chem., 2017, 60 (9), pp 4036-4046 DOI: 10.1021/acs.jmedchem.7b00366
- Johnson et al., “Fragment-to-Lead Medicinal Chemistry Publications in 2015.” J. Med. Chem., 2017, 60 (1), pp 89–99 DOI: 10.1021/acs.jmedchem.6b01123
2016
- Tisi et al., “Structure of the Epigenetic Oncogene MMSET and Inhibition by N-Alkyl Sinefungin Derivatives.” ACS Chem. Biol., 2016, 11 (11), pp 3093–3105 DOI: 10.1021/acschembio.6b00308
- Woolford et al., “Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2).” J. Med. Chem., 2016, 59 (23), pp 10738–10749 DOI: 10.1021/acs.jmedchem.6b01427
- Lebraud et al. “Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras.” ACS Cent. Sci.,2016, 2 (12), pp 927–934 DOI: 10.1021/acscentsci.6b00280
- Erlanson et al.. “Twenty years on: the impact of fragments on drug discovery.” Nature Reviews Drug Discovery (2016) DOI: 10.1038/nrd.2016.109
- Lebraud et al.. “In-gel activity-based protein profiling of a clickable covalent ERK1/2 inhibitor .” Mol. BioSyst., 2016,12, 2867-2874 DOI: 10.1039/C6MB00367B
- Verdonk et al. “Protein–Ligand Informatics Force Field (PLIff): Toward a Fully Knowledge Driven “Force Field” for Biomolecular Interactions.” J. Med. Chem., 2016, 59 (14), pp 6891–6902 DOI: 10.1021/acs.jmedchem.6b00716 View software
- Amin et al. “NMR backbone resonance assignment and solution secondary structure determination of human NSD1 and NSD2.” Biomol NMR Assign, 29 June 2016 DOI: 10.1007/s12104-016-9691-x
- Keserü et al. “Design Principles for Fragment Libraries: Maximizing the Value of Learnings from Pharma Fragment-Based Drug Discovery (FBDD) Programs for Use in Academia.” J. Med. Chem. April 2016 10.1021/acs.jmedchem.6b00197
- Woolford et al. “Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening.” J Med Chem, 27 May 2016 DOI: 10.1021/acs.jmedchem.6b00212
- Davies et al. “Mono-acidic inhibitors of the KEAP1 Kelch-NRF2 protein-protein interaction with high cell potency identified by Fragment-based Discovery.” J Med Chem, 31 March 2016 DOI: 10.1021/acs.jmedchem.6b00228
- Palmer et al. “Design and synthesis of dihydroisoquinolones for fragment-based drug discovery (FBDD) .” Org. Biomol. Chem., 2016,14, 1599-1610 PDF, 608 kB
More publications are viewable in the archive.
Presentations and Posters
2024
- 2024 ENA (poster): Pulsatile Induction of the p53 Pathway by MDM2 Antagonist ASTX295 Shows an Enhanced Therapeutic Index in vivo
- 2024 ENA (poster): A Novel Small-Molecule CBP/p300 HAT Domain Inhibitor Demonstrates Potent In Vivo Activity and a Favourable Safety Profile in Preclinical Species
- 2024 ENA (poster): Targeting the Catalytic HAT Domain of CBP/p300 for the Treatment of Hormone-Dependent Breast and Prostate Cancers
- 2024 ENA (poster): Identification of Biomarkers Predictive of Response to ASTX295, a Next-Generation MDM2 Antagonist, in Solid Tumors Carrying Wild-type p53
- 2024 ESMO (poster): Activity of ERK1/2 Inhibitor ASTX029 in Patients with Gynecological Malignancies Harboring Genomic Alterations in the MAPK Pathway
- 2024 AACR (oral): Discovery of ASTX295, a potent, next-generation small molecule antagonist of MDM2 with differentiated pharmacokinetic profile. From concept to clinic.
- 2024 AACR (poster): Identification of biomarkers of response to MDM2 inhibition in solid tumours using computational, multi-omics approaches.
- 2024 AACR (poster): Phase 1 study of MDM2 antagonist ASTX295 in patients with solid tumors with wild-type TP53
- 2024 AACR (poster): Targeting the MDM2-p53 interaction: Time-and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index
2023
2022
- EORTC Poster (2022): Low SKP2 expression is predictive of sensitivity to an MDM2 antagonist in p53 wild-type AML
- 2022 EHA – Combining the IAP antagonist, tolinapant, with a DNA hypomethylating agent enhances anti-tumour mechanisms in preclinical models of T-cell lymphoma
2021
2020
- 2020 EORTC-NCI-AACR: The non-peptidomimetic cIAP1/2 and XIAP antagonist tolinapant promotes an anti-tumour immune response in T-cell lymphoma
- Identification of potent small molecule allosteric inhibitors of SHP2
- Combined inhibition of SHP2 and ERK enhances anti-tumor effects in preclinical models
- The clinical candidate, ASTX029, is a novel, dual mechanism ERK1/2 Inhibitor and has potent activity in MAPK-activated cancer cell lines and in vivo tumor models
- 2020 AACR: Fragment-based drug discovery to identify small molecule allosteric inhibitors of SHP2
- 2020 AACR: ASTX660, a non-peptidomimetic antagonist of cIAP1/2 and XIAP, promotes an anti-tumor immune response in pre-clinical models of T-cell lymphoma
- 2020 AACR: Different pharmacodynamic profiles of ERK1/2 inhibition can elicit comparable anti-tumor activity
- 2020 EHA: Characterization of ASTX660, an antagonist of cIAP1/2 and XIAP, in mouse models of T cell lymphoma
- 2020 EHA: ASTX295, a novel small molecule MDM2 antagonist, demonstrates potent activity in AML in combination with decitabine
2019
2018
- 2018 EORTC: A novel ERK1/2 inhibitor has potent activity in NRAS-mutant melanoma cancer models
- 2018 AACR: Development of a potent class of small molecule inhibitors of the MDM2-p53 protein-protein interaction
More posters are viewable in the archive.
Interactive Publications
Overlay pages provide an interactive way of viewing 3D protein-ligand structures from X-ray or CryoEM. Related structures are organized and superimposed to enable easy comparison.
Software developed by Astex scientists that we hope will be of use to the drug discovery community.
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