Literature DB >> 23858438

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro.

Chris Mahony1, Lynda Erskine, Jennifer Niven, Nigel H Greig, William Douglas Figg, Neil Vargesson.   

Abstract

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.

Entities:  

Keywords:  CPS49; Cox2; cytoskeleton; drug screening

Mesh:

Substances:

Year:  2013        PMID: 23858438      PMCID: PMC3732931          DOI: 10.1073/pnas.1307684110

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  41 in total

Review 1.  The clinical safety of lenalidomide in multiple myeloma and myelodysplastic syndromes.

Authors:  Antonio Palumbo; John Freeman; Lilia Weiss; Pierre Fenaux
Journal:  Expert Opin Drug Saf       Date:  2011-11-09       Impact factor: 4.250

Review 2.  Management of treatment-emergent peripheral neuropathy in multiple myeloma.

Authors:  P G Richardson; M Delforge; M Beksac; P Wen; J L Jongen; O Sezer; E Terpos; N Munshi; A Palumbo; S V Rajkumar; J L Harousseau; P Moreau; H Avet-Loiseau; J H Lee; M Cavo; G Merlini; P Voorhees; W J Chng; A Mazumder; S Usmani; H Einsele; R Comenzo; R Orlowski; D Vesole; J J Lahuerta; R Niesvizky; D Siegel; M-V Mateos; M Dimopoulos; S Lonial; S Jagannath; J Bladé; J San Miguel; G Morgan; K C Anderson; B G M Durie; P Sonneveld
Journal:  Leukemia       Date:  2011-12-23       Impact factor: 11.528

3.  Identification of a primary target of thalidomide teratogenicity.

Authors:  Takumi Ito; Hideki Ando; Takayuki Suzuki; Toshihiko Ogura; Kentaro Hotta; Yoshimasa Imamura; Yuki Yamaguchi; Hiroshi Handa
Journal:  Science       Date:  2010-03-12       Impact factor: 47.728

Review 4.  Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues.

Authors:  Michel Delforge; Joan Bladé; Meletios A Dimopoulos; Thierry Facon; Martin Kropff; Heinz Ludwig; Antonio Palumbo; Philip Van Damme; Jesús F San-Miguel; Pieter Sonneveld
Journal:  Lancet Oncol       Date:  2010-11       Impact factor: 41.316

Review 5.  Antiangiogenic therapeutic approaches in multiple myeloma.

Authors:  Domenico Ribatti; Giuseppe Mangialardi; Angelo Vacca
Journal:  Curr Cancer Drug Targets       Date:  2012-09       Impact factor: 3.428

6.  Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide.

Authors:  Makoto Ema; Ryota Ise; Hirohito Kato; Satoru Oneda; Akihiko Hirose; Mutsuko Hirata-Koizumi; Amar V Singh; Thomas B Knudsen; Toshio Ihara
Journal:  Reprod Toxicol       Date:  2009-09-12       Impact factor: 3.143

7.  Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.

Authors:  A Lopez-Girona; D Mendy; T Ito; K Miller; A K Gandhi; J Kang; S Karasawa; G Carmel; P Jackson; M Abbasian; A Mahmoudi; B Cathers; E Rychak; S Gaidarova; R Chen; P H Schafer; H Handa; T O Daniel; J F Evans; R Chopra
Journal:  Leukemia       Date:  2012-05-03       Impact factor: 11.528

8.  Nitric oxide rescues thalidomide mediated teratogenicity.

Authors:  Jamila H Siamwala; Vimal Veeriah; M Krishna Priya; Saranya Rajendran; Uttara Saran; Swaraj Sinha; Shunmugam Nagarajan; T Pradeep; Suvro Chatterjee
Journal:  Sci Rep       Date:  2012-09-20       Impact factor: 4.379

9.  VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm.

Authors:  Lynda Erskine; Susan Reijntjes; Thomas Pratt; Laura Denti; Quenten Schwarz; Joaquim M Vieira; Bennett Alakakone; Derryck Shewan; Christiana Ruhrberg
Journal:  Neuron       Date:  2011-06-09       Impact factor: 17.173

10.  Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells.

Authors:  Kesavan Meganathan; Smita Jagtap; Vilas Wagh; Johannes Winkler; John Antonydas Gaspar; Diana Hildebrand; Maria Trusch; Karola Lehmann; Jürgen Hescheler; Hartmut Schlüter; Agapios Sachinidis
Journal:  PLoS One       Date:  2012-08-28       Impact factor: 3.240

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  29 in total

1.  Pomalidomide is teratogenic in rats and rabbits and can be neurotoxic in humans.

Authors:  Jerome B Zeldis; Troy L Carter; Robert D Knight; Julia Hui
Journal:  Proc Natl Acad Sci U S A       Date:  2013-12-03       Impact factor: 11.205

2.  Pomalidomide is strongly antiangiogenic and teratogenic in relevant animal models.

Authors:  Robert J D'Amato; Suzanne Lentzsch; Michael S Rogers
Journal:  Proc Natl Acad Sci U S A       Date:  2013-12-03       Impact factor: 11.205

3.  Reply to D’Amato et al. and Zeldis et al.: Screening of thalidomide derivatives in chicken and zebrafish embryos.

Authors:  Neil Vargesson; Chris Mahony; Lynda Erskine; Jennifer Niven; Nigel H Greig; William Douglas Figg
Journal:  Proc Natl Acad Sci U S A       Date:  2013-12-10       Impact factor: 11.205

4.  Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide.

Authors:  Goutam Chowdhury; Norio Shibata; Hiroshi Yamazaki; F Peter Guengerich
Journal:  Chem Res Toxicol       Date:  2013-12-24       Impact factor: 3.739

5.  A sensitive and robust HPLC assay with fluorescence detection for the quantification of pomalidomide in human plasma for pharmacokinetic analyses.

Authors:  Shandiz Shahbazi; Cody J Peer; Mark N Polizzotto; Thomas S Uldrick; Jeffrey Roth; Kathleen M Wyvill; Karen Aleman; Jerome B Zeldis; Robert Yarchoan; William D Figg
Journal:  J Pharm Biomed Anal       Date:  2014-01-09       Impact factor: 3.935

Review 6.  Advancing host-directed therapy for tuberculosis.

Authors:  Robert S Wallis; Richard Hafner
Journal:  Nat Rev Immunol       Date:  2015-03-13       Impact factor: 53.106

7.  Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.

Authors:  Ruth Eichner; Michael Heider; Vanesa Fernández-Sáiz; Frauke van Bebber; Anne-Kathrin Garz; Simone Lemeer; Martina Rudelius; Bianca-Sabrina Targosz; Laura Jacobs; Anna-Maria Knorn; Jolanta Slawska; Uwe Platzbecker; Ulrich Germing; Christian Langer; Stefan Knop; Herrmann Einsele; Christian Peschel; Christian Haass; Ulrich Keller; Bettina Schmid; Katharina S Götze; Bernhard Kuster; Florian Bassermann
Journal:  Nat Med       Date:  2016-06-13       Impact factor: 53.440

8.  Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues.

Authors:  Shaunna L Beedie; Cody J Peer; Steven Pisle; Erin R Gardner; Chris Mahony; Shelby Barnett; Agnieszka Ambrozak; Michael Gütschow; Cindy H Chau; Neil Vargesson; William D Figg
Journal:  Mol Cancer Ther       Date:  2015-08-12       Impact factor: 6.261

9.  CPS49-induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos.

Authors:  Chris Mahony; Scott McMenemy; Alexandra J Rafipay; Shaunna-Leigh Beedie; Lucas Rosa Fraga; Michael Gütschow; William D Figg; Lynda Erskine; Neil Vargesson
Journal:  J Anat       Date:  2017-10-10       Impact factor: 2.610

10.  Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities.

Authors:  Weiming Luo; David Tweedie; Shaunna L Beedie; Neil Vargesson; William D Figg; Nigel H Greig; Michael T Scerba
Journal:  Bioorg Med Chem       Date:  2018-02-10       Impact factor: 3.641

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