5ugc › Citations

Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR.

Planken S, Behenna DC, Nair SK, Johnson TO, Nagata A, Almaden C, Bailey S, Ballard TE, Bernier L, Cheng H, Cho-Schultz S, Dalvie D, Deal JG, Dinh DM, Edwards MP, Ferre RA, Gajiwala KS, Hemkens M, Kania RS, Kath JC, Matthews J, Murray BW, Niessen S, Orr ST, Pairish M, Sach NW, Shen H, Shi M, Solowiej J, Tran K, Tseng E, Vicini P, Wang Y, Weinrich SL, Zhou R, Zientek M, Liu L, Luo Y, Xin S, Zhang C, Lafontaine J
J Med Chem 60 3002-3019 (2017)
Related entries: 5ug8, 5ug9, 5uga, 5ugb

Cited: 31 times
EuropePMC logo PMID: 28287730

Abstract

Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (1), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants, was recently disclosed.1 Herein, we describe our continued efforts to achieve potency across EGFR oncogenic mutations and improved kinome selectivity, resulting in the discovery of clinical candidate PF-06747775 (21), which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. Compound 21 is currently being evaluated in phase-I clinical trials of mutant EGFR driven NSCLC.

Articles - 5ugc mentioned but not cited (10)

  1. Proteome-wide Map of Targets of T790M-EGFR-Directed Covalent Inhibitors. Niessen S, Dix MM, Barbas S, Potter ZE, Lu S, Brodsky O, Planken S, Behenna D, Almaden C, Gajiwala KS, Ryan K, Ferre R, Lazear MR, Hayward MM, Kath JC, Cravatt BF. Cell Chem Biol 24 1388-1400.e7 (2017)
  2. Complex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands. Niggenaber J, Heyden L, Grabe T, Müller MP, Lategahn J, Rauh D. ACS Med Chem Lett 11 2484-2490 (2020)
  3. Pharmacological targets and mechanisms of calycosin against meningitis. Nong Y, Liang Y, Liang X, Li Y, Yang B. Aging (Albany NY) 12 19468-19492 (2020)
  4. Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer. Huang C, Zhan L. Front Pharmacol 13 851540 (2022)
  5. Prediction of kinase inhibitors binding modes with machine learning and reduced descriptor sets. Abdelbaky I, Tayara H, Chong KT. Sci Rep 11 706 (2021)
  6. Anti-neoplastic characteristics and potential targets of calycosin against bisphenol A-related osteosarcoma: bioinformatics analysis. Pan Q, Wu K, Tan J, Li Y, Liang X, Su M. Bioengineered 12 4278-4288 (2021)
  7. Bioinformatics and in-silico findings reveal medical features and pharmacological targets of biochanin A against colorectal cancer and COVID-19. Qin J, Guo C, Yang L, Liang X, Jiao A, Lai KP, Lai KP, Yang B. Bioengineered 12 12461-12469 (2021)
  8. Exploring anti-liver cancer targets and mechanisms of oxyresveratrol: in silico and verified findings. Zhao F, Qin J, Liang Y, Zhou R. Bioengineered 12 9939-9948 (2021)
  9. Integrated Analysis Reveals the Targets and Mechanisms in Immunosuppressive Effect of Mesalazine on Ulcerative Colitis. Li R, Huang X, Yang L, Liang X, Huang W, Lai KP, Zhou L. Front Nutr 9 867692 (2022)
  10. Anti-Nasopharyngeal carcinoma mechanism of sanguinarine based on network pharmacology and molecular docking. Fan JY, Liu J, Zhang WQ, Lin T, Hu XR, Zhou FL, Tang L, He YC, Shi HJ. Medicine (Baltimore) 102 e36477 (2023)


Reviews citing this publication (9)

  1. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Wu SG, Shih JY. Mol Cancer 17 38 (2018)
  2. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Gelatti ACZ, Drilon A, Santini FC. Lung Cancer 137 113-122 (2019)
  3. Third generation EGFR TKIs: current data and future directions. Tan CS, Kumarakulasinghe NB, Huang YQ, Ang YLE, Choo JR, Goh BC, Soo RA. Mol Cancer 17 29 (2018)
  4. Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry. Lu X, Yu L, Zhang Z, Ren X, Smaill JB, Ding K. Med Res Rev 38 1550-1581 (2018)
  5. Third-generation epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. Andrews Wright NM, Goss GD. Transl Lung Cancer Res 8 S247-S264 (2019)
  6. Recent advances in activity-based probes (ABPs) and affinity-based probes (AfBPs) for profiling of enzymes. Fang H, Peng B, Ong SY, Wu Q, Li L, Yao SQ. Chem Sci 12 8288-8310 (2021)
  7. Urine test for EGFR analysis in patients with non-small cell lung cancer. Franovic A, Raymond VM, Erlander MG, Reckamp KL. J Thorac Dis 9 S1323-S1331 (2017)
  8. Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials. Xie X, Yu T, Li X, Zhang N, Foster LJ, Peng C, Huang W, He G. Signal Transduct Target Ther 8 335 (2023)
  9. The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies. Nitulescu GM, Stancov G, Seremet OC, Nitulescu G, Mihai DP, Duta-Bratu CG, Barbuceanu SF, Olaru OT. Molecules 28 5359 (2023)

Articles citing this publication (12)

  1. Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer. Bar-Peled L, Kemper EK, Suciu RM, Vinogradova EV, Backus KM, Horning BD, Paul TA, Ichu TA, Svensson RU, Olucha J, Chang MW, Kok BP, Zhu Z, Ihle NT, Dix MM, Jiang P, Hayward MM, Saez E, Shaw RJ, Cravatt BF. Cell 171 696-709.e23 (2017)
  2. Assessing Lysine and Cysteine Reactivities for Designing Targeted Covalent Kinase Inhibitors. Liu R, Yue Z, Tsai CC, Shen J. J Am Chem Soc 141 6553-6560 (2019)
  3. Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα. Borsari C, Keles E, McPhail JA, Schaefer A, Sriramaratnam R, Goch W, Schaefer T, De Pascale M, Bal W, Gstaiger M, Burke JE, Wymann MP. J Am Chem Soc 144 6326-6342 (2022)
  4. Identification of optimal dosing schedules of dacomitinib and osimertinib for a phase I/II trial in advanced EGFR-mutant non-small cell lung cancer. Poels KE, Schoenfeld AJ, Makhnin A, Tobi Y, Wang Y, Frisco-Cabanos H, Chakrabarti S, Shi M, Napoli C, McDonald TO, Tan W, Hata A, Weinrich SL, Yu HA, Michor F. Nat Commun 12 3697 (2021)
  5. Selective Covalent Targeting of Mutated EGFR(T790M) with Chlorofluoroacetamide-Pyrimidines. Sato M, Fuchida H, Shindo N, Kuwata K, Tokunaga K, Xiao-Lin G, Inamori R, Hosokawa K, Watari K, Shibata T, Matsunaga N, Koyanagi S, Ohdo S, Ono M, Ojida A. ACS Med Chem Lett 11 1137-1144 (2020)
  6. Allenamide as a bioisostere of acrylamide in the design and synthesis of targeted covalent inhibitors. Chen D, Guo D, Yan Z, Zhao Y. Medchemcomm 9 244-253 (2018)
  7. Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy. Michaels SA, Hulverson MA, Whitman GR, Tran LT, Choi R, Fan E, McNamara CW, Love MS, Ojo KK. Antimicrob Agents Chemother 66 e0001722 (2022)
  8. Tanshinone IIA promotes apoptosis by downregulating BCL2 and upregulating TP53 in triple-negative breast cancer. Liu J, Zhang C, Liu S, Wang X, Wu X, Hao J. Naunyn Schmiedebergs Arch Pharmacol 396 365-374 (2023)
  9. Discovery of Novel EGFR Inhibitor Targeting Wild-Type and Mutant Forms of EGFR: In Silico and In Vitro Study. Todsaporn D, Zubenko A, Kartsev V, Aiebchun T, Mahalapbutr P, Petrou A, Geronikaki A, Divaeva L, Chekrisheva V, Yildiz I, Choowongkomon K, Rungrotmongkol T. Molecules 28 3014 (2023)
  10. Highly diastereoselective synthesis of enantioenriched anti-α-allyl-β-fluoroamines. Chevis PJ, Wangngae S, Thaima T, Carroll AW, Willis AC, Pattarawarapan M, Pyne SG. Chem Commun (Camb) 55 6050-6053 (2019)
  11. Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid. Lahiani A, Haham-Geula D, Lankri D, Cornell-Kennon S, Schaefer EM, Tsvelikhovsky D, Lazarovici P. ACS Chem Neurosci 11 2577-2589 (2020)
  12. Thermal Stability and Utility of Dienes as Protecting Groups for Acrylamides. Hooper AR, Burns AS. ACS Med Chem Lett 13 833-840 (2022)


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