Seliciclib

Clinical trials and lab tests

Cancer treatment

Seliciclib has been found to produce apoptosis in treated cancerous cells of non-small cell lung cancer (NSCLC) and other cancers. Seliciclib has previously undergone Phase IIa clinical trials, in 240 NSCLC patients as a combined dose with existing first- and second-line treatments. In the current APPRAISE trial, the research drug is undergoing Phase IIb clinical trial as a monotherapy for NSCLC in third-line patients. The side-effects reported in Phase I trials of seliciclib for NSCLC were "nausea, vomiting, transient elevations in serum creatinine and liver function parameters and transient hypokalemia".

Immunological disorders

Seliciclib is also in clinical trials for B-cell lymphomas, including multiple myeloma. Seliciclib has been shown to inhibit RNA polymerase II-dependent transcription and down-regulation of the protein MCL1.

Seliciclib has been shown in vitro to induce apoptosis in neutrophil granulocytes. If this mechanism turns out to be safe, reliable and efficient in vivo, the drug could improve treatment of chronic inflammation diseases such as cystic fibrosis and arthritis. These are usually treated with glucocorticoids which often have serious side effects

Neurological therapies

In the nervous system, seliciclib has been shown to suppress microglial activation and to provide some neuroprotection in animal models of cerebral ischemia. Furthermore, it increases antitumor activity of temozolomide in treatment of glioblastoma multiforme and is considered as a possible therapeutic option for glioma.

Antiviral effect

Seliciclib is also a possible antiviral agent. It causes the death of cells infected with HIV and preventing the replication of herpes simplex virus.

Ovum production

Seliciclib has been shown to cause parthenogenetic egg activation. However it does create abnormal second polar bodies and therefore possible aneuploid zygotes. Egg activation usually involves calcium oscillations however this does not happen with seliciclib. Seciclib causes egg activation by inhibiting protein kinases which results in the inactivation of the maturation promoting factor (MPF).

Renal hypertrophy

Seliciclib reduces renal hypertrophy by 45% after 5/6 nephrectomy.

Side effects

Causes severe side effects that can not be tolerated on daily dosing. Side effects include hypokalemia and elevation of liver enzymes. Due to these side effects, seliciclib has not been approved by the USFDA.

References

References

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