• S. Sivamani Center for Genetic Studies & ResearchThe Madras Medical MissionChennai - 600037
  • Benin Joseph Division of Clinical Research, Beroe Consulting India Pvt. Ltd., Chennai -600097
  • Bibhas Kar Center for Genetic Studies & Research The Madras Medical Mission Chennai - 600037


The zebrafish is no doubt a powerful model organism with a combination of forward and reverse genetics, low cost, amenable high throughput, and
rapid in vivo analysis. With these unique features, it can be expected that the zebrafish will become more frequently used for drug discovery. This
review outlines the potential of zebrafish to contribute to drug discovery through the identification of novel drug targets, validation of those targets
and screening for new therapeutic compounds and assay development.
Keywords: Zebrafish, Drug screening, Drug target, Development.


1. Kar B, Sivamani S. Zebrafish: An in vivo model for the study of human
diseases. Int J Genet Genomics 2013;1(1):6-11.
2. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M,
et al. The zebrafish reference genome sequence and its relationship to
the human genome. Nature 2013;496(7446):498-503.
3. Rubinstein AL. Zebrafish assays for drug toxicity screening. Expert
Opin Drug Metab Toxicol 2006;2(2):231-40.
4. Kari G, Rodeck U, Dicker AP. Zebrafish: An emerging model
system for human disease and drug discovery. Clin Pharmacol Ther
5. Lieschke GJ, Currie PD. Animal models of human disease: Zebrafish
swim into view. Nat Rev Genet 2007;8(5):353-67.
6. Crawford AD, Esguerra CV, de Witte PA. Fishing for drugs from nature:
Zebrafish as a technology platform for natural product discovery. Planta
Med 2008;74(6):624-32.
7. Berghmans S, Butler P, Goldsmith P, Waldron G, Gardner I, Golder Z,
et al. Zebrafish based assays for the assessment of cardiac, visual
and gut function – Potential safety screens for early drug discovery.
J Pharmacol Toxicol Methods 2008;58(1):59-68.
8. McGrath P, Li CQ. Zebrafish: A predictive model for assessing druginduced
Drug Discov Today
9. Peterson RT, Link BA, Dowling JE, Schreiber SL. Small molecule
developmental screens reveal the logic and timing of vertebrate
development. Proc Natl Acad Sci U S A 2000;97(24):12965-9.
10. Hill AJ, Teraoka H, Heideman W, Peterson RE. Zebrafish as a model
vertebrate for investigating chemical toxicity. Toxicol Sci 2005;86(1):6-19.
11. Rong Z, Yin H. A method for genotoxicity detection using random
Asian J Pharm Clin Res, Vol 9, Issue 4, 2016, 11-14
Sivamani et al.
amplified polymorphism DNA with Danio rerio. Ecotoxicol Environ
Saf 2004;58(1):96-103.
12. Kosmehl T, Hallare AV, Reifferscheid G, Manz W, Braunbeck T,
Hollert H. A novel contact assay for testing genotoxicity of chemicals
and whole sediments in zebrafish embryos. Environ Toxicol Chem
13. Belyaeva NF, Kashirtseva VN, Medvedeva NV, Khudoklinova II,
Ipatova OM, Archakov AI. Zebrafish as a model system for biomedical
studies. Archakov Biochem (Mosc) Suppl Ser B Biomed Chem
14. Rubinstein AL. Zebrafish: From disease modeling to drug discovery.
Curr Opin Drug Discov Devel 2003;6(2):218-23.
15. Murphey RD, Zon LI. Small molecule screening in the zebrafish.
Methods 2006;39(3):255-61.
16. Berger J, Currie P. The role of zebrafish in chemical genetics. Curr Med
Chem 2007;14(22):2413-20.
17. Gibert Y, Trengove MC, Ward AC. Zebrafish as a genetic model in preclinical
drug testing and screening. Curr Med Chem 2013;20(19):2458-66.
18. Zon LI, Peterson RT. In vivo drug discovery in the zebrafish. Nat Rev
Drug Discov 2005;4(1):35-44.
19. Foley JE, Yeh JR, Maeder ML, Reyon D, Sander JD, Peterson RT,
et al. Rapid mutation of endogenous zebrafish genes using zinc finger
nucleases made by Oligomerized Pool Engineering (OPEN). PLoS One
20. Foley JE, Maeder ML, Pearlberg J, Joung JK, Peterson RT, Yeh JR.
Targeted mutagenesis in zebrafish using customized zinc-finger
nucleases. Nat Protoc 2009;4(12):1855-67.
21. Spring DR, Krishnan S, Blackwell HE, Schreiber SL. Diversityoriented
of biaryl-containing medium
rings using a one bead/
stock solution platform. J
Chem Soc 2002;124(7):1354-63.
22. MacRae CA, Peterson RT. Zebrafish-based small molecule discovery.
Chem Biol 2003;10(10):901-8.
23. Darland T, Dowling JE. Behavioral screening for cocaine sensitivity in
mutagenized zebrafish. Proc Natl Acad Sci U S A 2001;98(20):11691-6.
24. Guo S, Wilson SW, Cooke S, Chitnis AB, Driever W, Rosenthal A.
Mutations in the zebrafish unmask shared regulatory pathways
controlling the development of catecholaminergic neurons. Dev Biol
25. Hanumanthaiah R, Day K, Jagadeeswaran P. Comprehensive analysis
of blood coagulation pathways in teleostei: Evolution of coagulation
factor genes and identification of zebrafish factor VIIi. Blood Cells Mol
Dis 2002;29(1):57-68.
26. Farber SA, Pack M, Ho SY, Johnson ID, Wagner DS, Dosch R, et al.
Genetic analysis of digestive physiology using fluorescent phospholipid
reporters. Science 2001;292(5520):1385-8.
27. Jung DW, Williams D, Khersonsky SM, Kang TW, Heidary N,
Chang YT, et al. Identification of the F1F0 mitochondrial ATPase as a
target for modulating skin pigmentation by screening a tagged triazine
library in zebrafish. Mol Biosyst 2005;1(1):85-92.
28. Deiters A, Yoder JA. Conditional transgene and gene targeting
methodologies in zebrafish. Zebrafish 2006;3(4):415-29.
29. Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G. Zebrafish:
A complete animal model for in vivo drug discovery and development.
Curr Drug Metab 2009;10(2):116-24.
30. Delvecchio C, Tiefenbach J, Krause HM. The zebrafish: A powerful
platform for in vivo, HTS drug discovery. Assay Drug Dev Technol
31. Barros TP, Alderton WK, Reynolds HM, Roach AG, Berghmans S.
Zebrafish: An emerging technology for in vivo pharmacological
assessment to identify potential safety liabilities in early drug discovery.
Br J Pharmacol 2008;154(7):1400-13.
32. Sipes NS, Padilla S, Knudsen TB. Zebrafish: As an integrative model
for twenty-first century toxicity testing. Birth Defects Res C Embryo
Today 2011;93(3):256-67.
33. Lam SH, Gong Z. Fish as a model for human disease. In: Speicher MR,
Antonarakis SE, Motulsky AG, editors. Vogel and Motulsky’s Human
Genetics: Problems and Approaches. Berlin Heidelberg: SpringerVerlag;
34. Shin J, Padmanabhan A, de Groh ED, Lee JS, Haidar S, Dahlberg S,
et al. Zebrafish neurofibromatosis type 1 genes have redundant
functions in tumorigenesis and embryonic development. Dis Model
Mech 2012;5(6):881-94.
35. Koch L. Zebrafish models ultra-rare X-linked diseases. Nat Rev Genet
36. Whalley K. Psychiatric disorders: A zebrafish model of ADHD. Nat
Rev Neurosci 2015;16(4):188.
37. Mathias JR, Saxena MT, Mumm JS. Advances in zebrafish chemical
screening technologies. Future Med Chem 2012;4(14):1811-22.
38. Sachidanandan C, Yeh JR, Peterson QP, Peterson RT. Identification of
a novel retinoid by small molecule screening with zebrafish embryos.
PLoS One 2008;3(4):e1947.
39. Mathew LK, Sengupta S, Kawakami A, Andreasen EA, Löhr CV,
Loynes CA, et al. Unraveling tissue regeneration pathways using
chemical genetics. J Biol Chem 2007;282(48):35202-10.
40. Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA,
et al. Dorsomorphin inhibits BMP signals required for embryogenesis
and iron metabolism. Nat Chem Biol 2008;4(1):33-41.
41. Milan DJ, Peterson TA, Ruskin JN, Peterson RT, MacRae CA. Drugs
that induce repolarization abnormalities cause bradycardia in zebrafish.
Circulation 2003;107(10):1355-8.
42. Goldsmith P. Modelling eye diseases in zebrafish. Neuroreport
43. Baier H. Zebrafish on the move: Towards a behavior-genetic analysis of
vertebrate vision. Curr Opin Neurobiol 2000;10(4):451-5.
44. Sallinen V, Torkko V, Sundvik M, Reenilä I, Khrustalyov D, Kaslin J,
et al. MPTP and MPP target specific aminergic cell populations in
larval zebrafish. J Neurochem 2009;108(3):719-31.
45. Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, et al.
Zebrafish behavioral profiling links drugs to biological targets and rest/
wake regulation. Science 2010;327(5963):348-51.
46. Coffin AB, Ou H, Owens KN, Santos F, Simon JA, Rubel EW, et al.
Chemical screening for hair cell loss and protection in the zebrafish
lateral line. Zebrafish 2010;7(1):3-11.
47. Ton C, Lin Y, Willett C. Zebrafish as a model for developmental
neurotoxicity testing. Birth Defects Res A Clin Mol Teratol
48. Clifton JD, Lucumi E, Myers MC, Napper A, Hama K, Farber SA,
et al. Identification of novel inhibitors of dietary lipid absorption using
zebrafish. PLoS One 2010;5(8):e12386.
49. Ridges S, Heaton WL, Joshi D, Choi H, Eiring A, Batchelor L, et al.
Zebrafish screen identifies novel compound with selective toxicity
against leukemia. Blood 2012;119(24):5621-31.
50. Wang C, Tao W, Wang Y, Bikow J, Lu B, Keating A, et al. Rosuvastatin,
identified from a zebrafish chemical genetic screen for antiangiogenic
compounds, suppresses the growth of prostate cancer. Eur Urol
51. Lawson ND, Weinstein BM. In vivo imaging of embryonic vascular
development using transgenic zebrafish. Dev Biol 2002;248(2):307-18.
52. Gaj T, Gersbach CA, Barbas CF 3
Cas-based methods for genome engineering. Trends Biotechnol
53. Hsu CH, Wen ZH, Lin CS, Chakraborty C. The zebrafish model: Use in
studying cellular mechanisms for a spectrum of clinical disease entities.
Curr Neurovasc Res 2007;4(2):111-20.
366 Views | 539 Downloads
How to Cite
S. Sivamani, B. Joseph, and B. Kar. “ZEBRAFISH: AN EMERGING MODEL SYSTEM FOR DRUG DISCOVERY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 4, July 2016, pp. 11-14, https://innovareacademics.in/journals/index.php/ajpcr/article/view/9861.
Review Article(s)