Xiaolan Zheng

Publications (7)20.7 Total impact

• Article: Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases.

  Les A Dakin, Michael H Block, Huawei Chen, Erin Code, James E Dowling, Xiaomei Feng, Andrew D Ferguson, Isabelle Green, Alexander W Hird, Tina Howard, Erika K Keeton, Michelle L Lamb, Paul D Lyne, Hannah Pollard, Jon Read, Allan J Wu, Tao Zhang, Xiaolan Zheng
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  ABSTRACT: Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data.
  Bioorganic & medicinal chemistry letters 06/2012; 22(14):4599-604. · 2.65 Impact Factor
• Article: Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a kinesin spindle protein inhibitor and potential anticancer agent.

  Maria-Elena Theoclitou, Brian Aquila, Michael H Block, Patrick J Brassil, Lillian Castriotta, Erin Code, Michael P Collins, Audrey M Davies, Tracy Deegan, Jayachandran Ezhuthachan, [......], Deborah Lawson, Paula M Lewis, Murali V P Nadella, Vibha Oza, Maniyan Padmanilayam, Timothy Pontz, Lucienne Ronco, Daniel Russell, David Whitston, Xiaolan Zheng
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  ABSTRACT: Structure-activity relationship analysis identified (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP) inhibitors, as exhibiting both excellent biochemical potency and pharmaceutical properties suitable for clinical development. The selected compound arrested cells in mitosis leading to the formation of the monopolar spindle phenotype characteristic of KSP inhibition and induction of cellular death. A favorable pharmacokinetic profile and notable in vivo efficacy supported the selection of this compound as a clinical candidate for the treatment of cancer.
  Journal of Medicinal Chemistry 09/2011; 54(19):6734-50. · 4.80 Impact Factor
• Article: 3-amido-4-anilinocinnolines as a novel class of CSF-1R inhibitor.

  David A Scott, Les A Dakin, David J Del Valle, R Bruce Diebold, Lisa Drew, Thomas W Gero, Claude A Ogoe, Charles A Omer, Galina Repik, Kumar Thakur, Qing Ye, Xiaolan Zheng
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  ABSTRACT: 3-Amido-4-anilinocinnolines have been identified as potent and highly selective inhibitors of CSF-1R. The synthesis and SAR of these compounds is reported, along with some physical property, pharmacokinetic and kinase selectivity data.
  Bioorganic & medicinal chemistry letters 03/2011; 21(5):1382-4. · 2.65 Impact Factor
• Article: Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to lead exploration.

  Vibha Oza, Susan Ashwell, Patrick Brassil, Jason Breed, Chun Deng, Jay Ezhuthachan, Heather Haye, Candice Horn, James Janetka, Paul Lyne, [......], Sian Roswell, Mei Su, Dorin Toader, Dingwei Yu, Yan Yu, Anna Valentine, Peter Webborn, Ann White, Sonya Zabludoff, Xiaolan Zheng
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  ABSTRACT: Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described.
  Bioorganic & medicinal chemistry letters 09/2010; 20(17):5133-8. · 2.65 Impact Factor
• Article: 3-amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile.

  David A Scott, Kirsten J Bell, Cheryl T Campbell, Donald J Cook, Les A Dakin, David J Del Valle, Lisa Drew, Thomas W Gero, Maureen M Hattersley, Charles A Omer, Boris Tyurin, Xiaolan Zheng
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  ABSTRACT: The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF-1R kinase inhibitors is described. The series has excellent activity and kinase selectivity. Excellent physical properties and rodent PK profiles were achieved through the introduction of cyclic amines at the quinoline 6-position. Compounds with good activity in a mouse PD model measuring inhibition of pCSF-1R were identified.
  Bioorganic & medicinal chemistry letters 01/2009; 19(3):701-5. · 2.65 Impact Factor
• Article: Identification of amidoheteroaryls as potent inhibitors of mutant (V600E) B-Raf kinase with in vivo activity.

  Paul D Lyne, Brian Aquila, Donald J Cook, Les A Dakin, Jay Ezhuthachan, Stephanos Ioannidis, Timothy Pontz, Mei Su, Qing Ye, Xiaolan Zheng, Michael H Block, Scott Cowen, Tracy L Deegan, John W Lee, David A Scott, Dominique Custeau, Lisa Drew, Srinivasu Poondru, Minhui Shen, Allan Wu
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  ABSTRACT: A series of amidoheteroaryl compounds were designed and synthesized as inhibitors of B-Raf kinase. Several compounds from the series show excellent potency in biochemical, phenotypic and mode of action cellular assays. Potent examples from the series have also demonstrated good plasma exposure following an oral dose in rodents and activity against the Ras-Raf pathway in tumor bearing mice.
  Bioorganic & medicinal chemistry letters 11/2008; 19(3):1026-9. · 2.65 Impact Factor
• Article: Pyridyl and thiazolyl bisamide CSF-1R inhibitors for the treatment of cancer.

  David A Scott, Brian M Aquila, Geraldine A Bebernitz, Donald J Cook, Les A Dakin, Tracy L Deegan, Maureen M Hattersley, Stephanos Ioannidis, Paul D Lyne, Charles A Omer, Minwei Ye, Xiaolan Zheng
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  ABSTRACT: The bisamide class of kinase inhibitors was identified as being active against CSF-1R. The synthesis and SAR of pyridyl and thiazolyl bisamides are reported, along with the pharmacokinetic properties and in vivo activity of selected examples.
  Bioorganic & medicinal chemistry letters 10/2008; 18(17):4794-7. · 2.65 Impact Factor