Preliminary safety evaluation of novel small molecule inhibitors of caspase-3

Samiulla, D. S.; Naidu, A.; Ramachandra, M.
June 2012
Journal of Chemical & Pharmaceutical Research;2012, Vol. 4 Issue 6, p3129
Academic Journal
Caspase inhibition was known to be therapeutically effective in treating the excessive programmed cell death related disorders. We investigated the novel, potent and irreversible small molecules inhibitors of caspase-3 having reasonable selectivity, ADME properties and pharmacologically active compounds for in-vitro cytotoxicity test and in-vivo acute tolerated studies in male balb-c mice. Preliminary safety assessment indicates that maximum safest concentration in the in-vitro test using freshly isolated rat primary hepatocytes was up-to 30μM for all the tested compounds. Interestingly, compound 3D displayed advantage (3fold) in protecting the hepatocytes toxicity when cells were treated with flavopiridol (flavonoid as pan-CDK inhibitor). It also exhibited non-significant changes in behavior of animals, body weight loss, gross pathology, plasma ALT and AST levels when administered orally at 30 mg/kg dose. These results support further development of compound 3D as a potential anti-apoptotic agent.


Related Articles

  • Retraction: INrf2 (Keap1) targets Bcl-2 degradation and controls cellular apoptosis. Niture, S K; Jaiswal, A K // Cell Death & Differentiation;Mar2014, Vol. 21 Issue 3, p503 

    A correction to the article "INrf2 (Keap1) targets Bcl-2 Degradation and Controls Cellular Apoptosis" is presented which discusses the clinical experiments on degradation.

  • An attack on aging. Gorman, Christine // Time;1/26/1998, Vol. 151 Issue 3, p60 

    Points out how scientists have discovered how an enzyme called telomere can revive dying cells. The experiment, which is sponsored by the US National Institute of Aging and the Geron biotech company of Menlo Park, California, as appearing in the journal `Science'; The evidence that each of the...

  • Preventing cells from committing suicide.  // USA Today Magazine;Jun98, Vol. 126 Issue 2637, p4 

    Focuses on the prevention of apoptosis or programmed cell death. Why human cells commit suicide; Advantage of apoptosis; Factor that triggers cellular suicide.

  • Suicidal brain cells can be saved. Knight, Jonathan // New Scientist;05/09/98, Vol. 158 Issue 2133, p21 

    Reports that a way has been found to reduce the damage to brain cells temporarily deprived of oxygen. Discovery that brain cells do not die as soon as they are deprived of oxygen; Length of time that cells can survive without oxygen; Description of apoptosis, or cell suicide; Enzymes called...

  • An attack on aging. Gorman, Christine // Time International (South Pacific Edition);01/26/98, Issue 4, p53 

    Points out how scientists have discovered how an enzyme called telomerase can revive dying cells. The experiment, which is sponsored by the US National Institute on Aging and the Geron biotech company of Menlo Park, California, as appearing in the journal `Science'; The evidence that each of...

  • Neuroprotection not yet a clinical reality. Charters, Lynda; Katz, L. Jay // Ophthalmology Times;06/15/2001, Vol. 26 Issue 12, p62 

    Provides information on neuroprotection, a technique in cell death prevention. Application of neuroprotection in preventing glaucomatous damage; Purpose of neuroprotection in glaucoma; Mechanism of action of some neuroprotective agents.

  • Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin. Chuang, Jih I; Chang, Tsuey Y; Liu, Hsiao S // Oncogene;3/6/2003, Vol. 22 Issue 9, p1349 

    It is well known that intracellular antioxidant glutathione (GSH) plays major roles in the maintenance of redox status and defense of oxidative stress. Ras, a small GTP-binding protein, may send growth-stimulating message to the nucleus through downstream Rac oncoprotein and superoxide (O2-)....

  • Radiation-induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z-VAD-fmk in the hypoglossal nucleus. JIANGUO LI; YAN WANG; LIQING DU; CHANG XU; JIA CAO; QIN WANG; QIANG LIU; FEIYUE FAN // Experimental & Therapeutic Medicine;2014, Vol. 7 Issue 2, p383 

    Numerous studies have demonstrated that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. To investigate the role of caspase, a cell permeable pan-caspase inhibitor,...

  • Caspase-3 is Involved in IFN-γ- and TNF-α-Mediated MIN6 Cells Apoptosis via NF-κB/Bcl-2 Pathway. Cao, Zhao-hui; Yin, Wei-dong; Zheng, Quan-you; Feng, Shao-long; Xu, Gui-lian; Zhang, Ke-qin // Cell Biochemistry & Biophysics;Dec2013, Vol. 67 Issue 3, p1239 

    TNF-α and IFN-γ are the major pro-inflammatory cytokines in the β-cell destruction. However, the underlying mechanism remains unclear. The present study used a murine insulinoma cell line MIN6 for further investigation of the effect of Caspase-3 on the cytokines-induced pancreatic...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics