Full Text Journal Articles by
Author J Russell Lipford

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Prospecting for molecular glues.

Willem den Besten, J Russell Lipford,

Nat Chem Biol (Nature chemical biology)
[2020, 16(11):1157-1158]

Cited: 0 times

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KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.

David S Hong, Marwan G Fakih, John H Strickler, Jayesh Desai, Gregory A Durm, Geoffrey I Shapiro, Gerald S Falchook, Timothy J Price, Adrian Sacher, Crystal S Denlinger, Yung-Jue Bang, Grace K Dy, John C Krauss, Yasutoshi Kuboki, James C Kuo, Andrew L Coveler, Keunchil Park, Tae Won Kim, Fabrice Barlesi, Pamela N Munster, Suresh S Ramalingam, Timothy F Burns, Funda Meric-Bernstam, Haby Henary, Jude Ngang, Gataree Ngarmchamnanrith, June Kim, Brett E Houk, Jude Canon, J Russell Lipford, Gregory Friberg, Piro Lito, Ramaswamy Govindan, Bob T Li,

BACKGROUND:No therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C. METHODS:We conducted a phase 1 ... Read more >>

N Engl J Med (The New England journal of medicine)
[2020, 383(13):1207-1217]

Cited: 0 times

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Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors.

Brian A Lanman, Jennifer R Allen, John G Allen, Albert K Amegadzie, Kate S Ashton, Shon K Booker, Jian Jeffrey Chen, Ning Chen, Michael J Frohn, Guy Goodman, David J Kopecky, Longbin Liu, Patricia Lopez, Jonathan D Low, Vu Ma, Ana E Minatti, Thomas T Nguyen, Nobuko Nishimura, Alexander J Pickrell, Anthony B Reed, Youngsook Shin, Aaron C Siegmund, Nuria A Tamayo, Christopher M Tegley, Mary C Walton, Hui-Ling Wang, Ryan P Wurz, May Xue, Kevin C Yang, Pragathi Achanta, Michael D Bartberger, Jude Canon, L Steven Hollis, John D McCarter, Christopher Mohr, Karen Rex, Anne Y Saiki, Tisha San Miguel, Laurie P Volak, Kevin H Wang, Douglas A Whittington, Stephan G Zech, J Russell Lipford, Victor J Cee,

KRASG12C has emerged as a promising target in the treatment of solid tumors. Covalent inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by this long-"undruggable" target; however clinically viable inhibitors have yet to be identified. Here, we report efforts to exploit a cryptic pocket (H95/Y96/Q99) we ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, 63(1):52-65]

Cited: 5 times

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Discovery of N-(1-Acryloylazetidin-3-yl)-2-(1H-indol-1-yl)acetamides as Covalent Inhibitors of KRASG12C.

Youngsook Shin, Joon Won Jeong, Ryan P Wurz, Pragathi Achanta, Tara Arvedson, Michael D Bartberger, Iain D G Campuzano, Ray Fucini, Stig K Hansen, John Ingersoll, Jeffrey S Iwig, J Russell Lipford, Vu Ma, David J Kopecky, John McCarter, Tisha San Miguel, Christopher Mohr, Sudi Sabet, Anne Y Saiki, Andrew Sawayama, Steven Sethofer, Christopher M Tegley, Laurie P Volak, Kevin Yang, Brian A Lanman, Daniel A Erlanson, Victor J Cee,

KRAS regulates many cellular processes including proliferation, survival, and differentiation. Point mutants of KRAS have long been known to be molecular drivers of cancer. KRAS p.G12C, which occurs in approximately 14% of lung adenocarcinomas, 3-5% of colorectal cancers, and low levels in other solid tumors, represents an attractive therapeutic target ... Read more >>

(ACS medicinal chemistry letters)
[2019, 10(9):1302-1308]

Cited: 2 times

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The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity.

Jude Canon, Karen Rex, Anne Y Saiki, Christopher Mohr, Keegan Cooke, Dhanashri Bagal, Kevin Gaida, Tyler Holt, Charles G Knutson, Neelima Koppada, Brian A Lanman, Jonathan Werner, Aaron S Rapaport, Tisha San Miguel, Roberto Ortiz, Tao Osgood, Ji-Rong Sun, Xiaochun Zhu, John D McCarter, Laurie P Volak, Brett E Houk, Marwan G Fakih, Bert H O'Neil, Timothy J Price, Gerald S Falchook, Jayesh Desai, James Kuo, Ramaswamy Govindan, David S Hong, Wenjun Ouyang, Haby Henary, Tara Arvedson, Victor J Cee, J Russell Lipford,

KRAS is the most frequently mutated oncogene in cancer and encodes a key signalling protein in tumours1,2. The KRAS(G12C) mutant has a cysteine residue that has been exploited to design covalent inhibitors that have promising preclinical activity3-5. Here we optimized a series of inhibitors, using novel binding interactions to markedly enhance their potency ... Read more >>

Nature (Nature)
[2019, 575(7781):217-223]

Cited: 42 times

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Discovery of ( R)-8-(6-Methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4- b]pyrrol-2-yl)-3-(1-methylcyclopropyl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3 H)-one, a Potent and Selective Pim-1/2 Kinase Inhibitor for Hematological Malignancies.

Hui-Ling Wang, Kristin L Andrews, Shon K Booker, Jude Canon, Victor J Cee, Frank Chavez, Yuping Chen, Heather Eastwood, Nadia Guerrero, Brad Herberich, Dean Hickman, Brian A Lanman, Jimmy Laszlo, Matthew R Lee, J Russell Lipford, Bethany Mattson, Christopher Mohr, Yen Nguyen, Mark H Norman, Liping H Pettus, David Powers, Anthony B Reed, Karen Rex, Christine Sastri, Nuria Tamayo, Paul Wang, Jeffrey T Winston, Bin Wu, Qiong Wu, Tian Wu, Ryan P Wurz, Yang Xu, Yihong Zhou, Andrew S Tasker,

Pim kinases are a family of constitutively active serine/threonine kinases that are partially redundant and regulate multiple pathways important for cell growth and survival. In human disease, high expression of the three Pim isoforms has been implicated in the progression of hematopoietic and solid tumor cancers, which suggests that Pim ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2019, 62(3):1523-1540]

Cited: 1 time

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A "Click Chemistry Platform" for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation.

Ryan P Wurz, Ken Dellamaggiore, Hannah Dou, Noelle Javier, Mei-Chu Lo, John D McCarter, Dane Mohl, Christine Sastri, J Russell Lipford, Victor J Cee,

Proteolysis targeting chimeras (PROTACs) are bispecific molecules containing a target protein binder and an ubiquitin ligase binder connected by a linker. By recruiting an ubiquitin ligase to a target protein, PROTACs promote ubiquitination and proteasomal degradation of the target protein. The generation of effective PROTACs depends on the nature of ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2018, 61(2):453-461]

Cited: 18 times

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Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors.

Ryan P Wurz, Christine Sastri, Derin C D'Amico, Brad Herberich, Claire L M Jackson, Liping H Pettus, Andrew S Tasker, Bin Wu, Nadia Guerrero, J Russell Lipford, Jeffrey T Winston, Yajing Yang, Paul Wang, Yen Nguyen, Kristin L Andrews, Xin Huang, Matthew R Lee, Christopher Mohr, J D Zhang, Darren L Reid, Yang Xu, Yihong Zhou, Hui-Ling Wang,

High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2016, 26(22):5580-5590]

Cited: 4 times

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Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable Pan-Pim Kinase Inhibitors.

Liping H Pettus, Kristin L Andrews, Shon K Booker, Jie Chen, Victor J Cee, Frank Chavez, Yuping Chen, Heather Eastwood, Nadia Guerrero, Bradley Herberich, Dean Hickman, Brian A Lanman, Jimmy Laszlo, Matthew R Lee, J Russell Lipford, Bethany Mattson, Christopher Mohr, Yen Nguyen, Mark H Norman, David Powers, Anthony B Reed, Karen Rex, Christine Sastri, Nuria Tamayo, Paul Wang, Jeffrey T Winston, Bin Wu, Tian Wu, Ryan P Wurz, Yang Xu, Yihong Zhou, Andrew S Tasker, Hui-Ling Wang,

The high expression of proviral insertion site of Moloney murine leukemia virus kinases (Pim-1, -2, and -3) in cancers, particularly the hematopoietic malignancies, is believed to play a role in promoting cell survival and proliferation while suppressing apoptosis. The three isoforms of Pim protein appear largely redundant in their oncogenic ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2016, 59(13):6407-6430]

Cited: 4 times

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Discovery and Optimization of Macrocyclic Quinoxaline-pyrrolo-dihydropiperidinones as Potent Pim-1/2 Kinase Inhibitors.

Victor J Cee, Frank Chavez, Bradley Herberich, Brian A Lanman, Liping H Pettus, Anthony B Reed, Bin Wu, Ryan P Wurz, Kristin L Andrews, Jie Chen, Dean Hickman, Jimmy Laszlo, Matthew R Lee, Nadia Guerrero, Bethany K Mattson, Yen Nguyen, Christopher Mohr, Karen Rex, Christine E Sastri, Paul Wang, Qiong Wu, Tian Wu, Yang Xu, Yihong Zhou, Jeffrey T Winston, J Russell Lipford, Andrew S Tasker, Hui-Ling Wang,

The identification of Pim-1/2 kinase overexpression in B-cell malignancies suggests that Pim kinase inhibitors will have utility in the treatment of lymphoma, leukemia, and multiple myeloma. Starting from a moderately potent quinoxaline-dihydropyrrolopiperidinone lead, we recognized the potential for macrocyclization and developed a series of 13-membered macrocycles. The structure-activity relationships of ... Read more >>

(ACS medicinal chemistry letters)
[2016, 7(4):408-412]

Cited: 2 times

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The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors.

Hui-Ling Wang, Victor J Cee, Frank Chavez, Brian A Lanman, Anthony B Reed, Bin Wu, Nadia Guerrero, J Russell Lipford, Christine Sastri, Jeff Winston, Kristin L Andrews, Xin Huang, Matthew R Lee, Christopher Mohr, Yang Xu, Yihong Zhou, Andrew S Tasker,

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to tumorigenesis. As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Herein, we describe our efforts toward the development of a potent, pan-Pim inhibitor. The ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2015, 25(4):834-840]

Cited: 8 times

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Discovery of 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines as potent PIM inhibitors.

Bin Wu, Hui-Ling Wang, Victor J Cee, Brian A Lanman, Thomas Nixey, Liping Pettus, Anthony B Reed, Ryan P Wurz, Nadia Guerrero, Christine Sastri, Jeff Winston, J Russell Lipford, Matthew R Lee, Christopher Mohr, Kristin L Andrews, Andrew S Tasker,

PIM kinases are a family of Ser/Thr kinases that are implicated in tumorigenesis. The discovery of a new class of PIM inhibitors, 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines, is discussed with optimized compounds showing excellent potency against all three PIM isoforms. ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2015, 25(4):775-780]

Cited: 7 times

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Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).

Adrian L Smith, Kristin L Andrews, Holger Beckmann, Steven F Bellon, Pedro J Beltran, Shon Booker, Hao Chen, Young-Ah Chung, Noel D D'Angelo, Jennifer Dao, Kenneth R Dellamaggiore, Peter Jaeckel, Richard Kendall, Katja Labitzke, Alexander M Long, Silvia Materna-Reichelt, Petia Mitchell, Mark H Norman, David Powers, Mark Rose, Paul L Shaffer, Michelle M Wu, J Russell Lipford,

The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo. ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2015, 58(3):1426-1441]

Cited: 14 times

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The discovery and optimization of aminooxadiazoles as potent Pim kinase inhibitors.

Ryan P Wurz, Liping H Pettus, Claire Jackson, Bin Wu, Hui-Ling Wang, Brad Herberich, Victor Cee, Brian A Lanman, Anthony B Reed, Frank Chavez, Thomas Nixey, Jimmy Laszlo, Paul Wang, Yen Nguyen, Christine Sastri, Nadia Guerrero, Jeff Winston, J Russell Lipford, Matthew R Lee, Kristin L Andrews, Christopher Mohr, Yang Xu, Yihong Zhou, Darren L Reid, Andrew S Tasker,

High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers. These findings suggest that inhibition of Pim signaling by a small molecule Pim-1,2 inhibitor could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal starting from the highly Pim-selective indole-thiadiazole compound ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2015, 25(4):847-855]

Cited: 4 times

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Unfolded Protein Response in Cancer: IRE1α Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability.

Paul E Harrington, Kaustav Biswas, David Malwitz, Andrew S Tasker, Christopher Mohr, Kristin L Andrews, Ken Dellamaggiore, Richard Kendall, Holger Beckmann, Peter Jaeckel, Silvia Materna-Reichelt, Jennifer R Allen, J Russell Lipford,

The kinase/endonuclease inositol requiring enzyme 1 (IRE1α), one of the sensors of unfolded protein accumulation in the endoplasmic reticulum that triggers the unfolded protein response (UPR), has been investigated as an anticancer target. We identified potent allosteric inhibitors of IRE1α endonuclease activity that bound to the kinase site on the ... Read more >>

(ACS medicinal chemistry letters)
[2015, 6(1):68-72]

Cited: 18 times

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Gal4 turnover and transcription activation.

Galen A Collins, J Russell Lipford, Raymond J Deshaies, William P Tansey,

Growing evidence supports the notion that proteasome-mediated destruction of transcriptional activators can be intimately coupled to their function. Recently, Nalley et al. challenged this view by reporting that the prototypical yeast activator Gal4 does not dynamically associate with chromatin, but rather 'locks in' to stable promoter complexes that are resistant ... Read more >>

Nature (Nature)
[2009, 461(7265):E7; discussion E8]

Cited: 16 times

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A putative stimulatory role for activator turnover in gene expression.

J Russell Lipford, Geoffrey T Smith, Yong Chi, Raymond J Deshaies,

The ubiquitin-proteasome system (UPS) promotes the destruction of target proteins by attaching to them a ubiquitin chain that is recognized by the 26S proteasome. The UPS influences most cellular processes, and its targets include transcriptional activators that are primary determinants of gene expression. Emerging evidence indicates that non-proteolytic functions of ... Read more >>

Nature (Nature)
[2005, 438(7064):113-116]

Cited: 112 times

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Analysis of polyubiquitin conjugates reveals that the Rpn10 substrate receptor contributes to the turnover of multiple proteasome targets.

Thibault Mayor, J Russell Lipford, Johannes Graumann, Geoffrey T Smith, Raymond J Deshaies,

The polyubiquitin receptor Rpn10 targets ubiquitylated Sic1 to the 26S proteasome for degradation. In contrast, turnover of at least one ubiquitin-proteasome system (UPS) substrate, CPY*, is impervious to deletion of RPN10. To distinguish whether RPN10 is involved in the turnover of only a small set of cell cycle regulators that ... Read more >>

Mol. Cell Proteomics (Molecular & cellular proteomics : MCP)
[2005, 4(6):741-751]

Cited: 63 times

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Diverse roles for ubiquitin-dependent proteolysis in transcriptional activation.

J Russell Lipford, Raymond J Deshaies,

A growing literature points to a fundamental role for the ubiquitin-proteasome degradation system (UPS) in transcription. Four recent publications add significant insight to our understanding of the connections between these processes. Each provides evidence that some aspect of the UPS can stimulate the activity of transcriptional activators. UPS might promote ... Read more >>

Nat. Cell Biol. (Nature cell biology)
[2003, 5(10):845-850]

Cited: 104 times

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