| Stereochemistry | ABSOLUTE |
| Molecular Formula | C28H39N7O3 |
| Molecular Weight | 521.6544 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC[C@H]1N(C2CCCC2)C3=NC(NC4=C(OC)C=C(C=C4)C(=O)NC5CCN(C)CC5)=NC=C3N(C)C1=O
InChI
InChIKey=XQVVPGYIWAGRNI-JOCHJYFZSA-N
InChI=1S/C28H39N7O3/c1-5-22-27(37)34(3)23-17-29-28(32-25(23)35(22)20-8-6-7-9-20)31-21-11-10-18(16-24(21)38-4)26(36)30-19-12-14-33(2)15-13-19/h10-11,16-17,19-20,22H,5-9,12-15H2,1-4H3,(H,30,36)(H,29,31,32)/t22-/m1/s1
BI-2536, an inhibitor of Polo-like kinase 1 (Plk-1) was being investigated by Boehringer Ingelheim as a possible treatment for cancer. BI-2536 inhibits Plk1 enzyme activity at low nanomolar concentrations. The compound potently causes a mitotic arrest and induces apoptosis in human cancer cell lines of diverse tissue origin and oncogenome signature. BI-2536 inhibits growth of human tumor xenografts in nude mice and induces regression of large tumors with well-tolerated intravenous dose regimens. In treated tumors, cells arrest in prometaphase, accumulate phosphohistone H3, and contain aberrant mitotic spindles. This mitotic arrest is followed by a surge in apoptosis, detectable by immunohistochemistry and noninvasive optical and magnetic resonance imaging. For addressing the therapeutic potential of Plk1 inhibition, BI-2536 has progressed into clinical studies in patients with locally advanced or metastatic cancers. It underwent phase II clinical studies for the treatment of breast cancer; non-small cell lung cancer; pancreatic cancer; prostate cancer; small cell lung cancer, but these studies were discontinued later.
Originator
Approval Year
Cmax
AUC
T1/2
Sourcing
PubMed
Patents
Sample Use Guides
200 mg of i.v. BI- 2536, administered once every 3 weeks in patients with advanced metastatic hormone-refractory prostate cancer
Route of Administration:
Intravenous
BI-2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes, dependent on Plk1 in HeLa cultures.
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
