9917. Valspodar

Nomenclature

CAS number: 121584-18-7
6-[(2S,4R,6E)-4-Methyl-2-(methylamino)-3-oxo-6-octenoic acid]cyclosporin D; [3′-desoxy-3′-oxo-MeBmt]1-[Val]2-cyclosporin; [3′-keto-Bmt1]-[Val2]-cyclosporin; PSC-833; SDZ-PSC-833; Amdray (Novartis).
C63H111N11O12; mol wt 1214.62.
C 62.30%, H 9.21%, N 12.68%, O 15.81%.

Description and references

Nonimmunosuppressive cyclosporin analog that reverses multidrug resistance (MDR) by inhibiting cellular drug efflux mediated by P-glycoprotein, q.v. Prepn: P. Bollinger et al., EP 296122; eidem, US 5525590 (1988, 1996 both to Sandoz). Pharmacology: D. Boesch et al., Exp. Cell Res. 196, 26 (1991). Clinical pharmacokinetics: R. M. Lush et al., J. Clin. Pharmacol. 37, 123 (1997). HPLC determn in blood: M. G. Scott et al., Clin. Chem. 43, 505 (1997). Clinical evaluation in multiple myeloma: P. Sonneveld et al., Leukemia 10, 1741 (1996); in acute myelogenous leukemia: R. Advani et al., Blood 93, 787 (1999). Review of pharmacology and clinical efficacy: F. Loor, Expert Opin. Invest. Drugs 8, 807-835 (1999).

Chemical structure

Properties

Insol in water. Sol in ethanol, DMSO. [α]D20 255.1° (c = 0.5 in CHCl3).

Therapeutic Category

Antineoplastic adjunct (chemosensitizer).

Keywords

Antineoplastic Adjunct; Chemosensitizer