Seliciclib

Seliciclib

Names
IUPAC name 2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine
Other names Roscovitine; CYC202
Identifiers
CAS Number	186692-46-6 Y
ChEMBL	ChEMBL14762 N
ChemSpider	140922 N
IUPHAR/BPS	6035
Jmol 3D model	Interactive image
MeSH	roscovitine
PubChem	160355
UNII	0ES1C2KQ94 N
InChI InChI=1S/C19H26N6O/c1-4-15(11-26)22-19-23-17(20-10-14-8-6-5-7-9-14)16-18(24-19)25(12-21-16)13(2)3/h5-9,12-13,15,26H,4,10-11H2,1-3H3,(H2,20,22,23,24)/t15-/m1/s1 N Key: BTIHMVBBUGXLCJ-OAHLLOKOSA-N N InChI=1/C19H26N6O/c1-4-15(11-26)22-19-23-17(20-10-14-8-6-5-7-9-14)16-18(24-19)25(12-21-16)13(2)3/h5-9,12-13,15,26H,4,10-11H2,1-3H3,(H2,20,22,23,24)/t15-/m1/s1 Key: BTIHMVBBUGXLCJ-OAHLLOKOBS
SMILES CC[C@H](CO)NC1=NC(=C2C(=N1)N(C=N2)C(C)C)NCC3=CC=CC=C3
Properties
Chemical formula	C19H26N6O
Molar mass	354.46 g·mol−1
Vapor pressure	{{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9, which alter the growth phase or state within the cell cycle of treated cells. Seliciclib is being developed by Cyclacel.

Seliciclib is being researched for the treatment of non-small cell lung cancer (NSCLC), Cushing's disease, leukemia, HIV infection, herpes simplex infection, cystic fibrosis and the mechanisms of chronic inflammation disorders.

Seliciclib is a 2,6,9-substituted purine analog. Its structure in complex with CDK2 was determined in 1996. Seliciclib inhibits CDK2/E, CDK2/A, CDK7 and CDK9.

Uses

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".

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

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.

Seliciclib has been shown to cause parthogenetic 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).