10293. Enzastaurin

Nomenclature

CAS number: 170364-57-5
3-(1-Methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione; LY-317615.
C32H29N5O2; mol wt 515.60.
C 74.54%, H 5.67%, N 13.58%, O 6.21%.

Description and references

Bisindolylmaleimide inhibitor of protein kinase Cβ (PKCβ), AKT, and GSK3β; structural analog of staurosporine, q.v. Prepn: W. F. Heath et al., WO 9517182; eidem, US 5668152 (1995, 1997 both to Lilly); M. M. Faul et al,. Tetrahedron 59, 7215 (2003) DOI. Inhibition of cell growth through the AKT pathway: J. R. Graff et al., Cancer Res. 65, 7462 (2005) DOI PubMed. In vivo and in vitro pharmacology in gastric cancer cells: K.-W. Lee et al., ibid. 68, 1916 (2008) DOI PubMed. Clinical pharmacology: P. A. Welch et al., J. Clin. Pharmacol. 47, 1138 (2007) DOI PubMed. Clinical evaulation in relapsed or refractory mantle cell lymphoma: F. Morschhauser et al., Ann. Oncol. 19, 247 (2008) DOI PubMed; in second- or third-line therapy of non-small-cell lung cancer: Y. Oh et al., J. Clin. Oncol. 26, 1135 (2008) DOI PubMed. Review of development, clinical experience, and therapeutic potential: R. S. Herbst et al., Clin. Cancer Res. 13, 4641s-4646s (2007) DOI PubMed.

Chemical structure

Properties

Orange solid.

Derivative

Hydrochloride.

Nomenclature

CAS number: 359017-79-1
C32H29N5O2.HCl; mol wt 552.07.
C 69.62%, H 5.48%, N 12.69%, O 5.80%, Cl 6.42%.

Description and references

Prepn: J. K. Bush et al., WO 04006928 (2004 to Lilly).

Properties

Crystals, mp ≈256°.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Alkaloids/Natural Products; Staurosporine Derivatives