cystine-dimethyl-ester and Cystinuria

Cystinuria, a genetic disorder of cystine transport, is characterized by excessive excretion of cystine in the urine and recurrent cystine stones in the kidneys and, to a lesser extent, in the bladder. Males generally are more severely affected than females. The disorder may lead to chronic kidney disease in many patients. The cystine transporter (b

Topics: Amino Acid Transport Systems, Basic; Amino Acid Transport Systems, Neutral; Animals; Chelating Agents; Clinical Trials as Topic; Cystine; Cystinuria; Disease Models, Animal; Drug Development; Female; Humans; Kidney; Kidney Calculi; Male; Mice; Mice, Knockout; Prevalence; Renal Elimination; Severity of Illness Index; Sex Factors

To overcome the chemical and metabolic stability issues of l-cystine dimethyl ester (CDME) and l-cystine methyl ester (CME), a series of l-cystine diamides with or without N

Topics: Amides; Crystallization; Cystine; Cystinuria; Kidney Calculi; Models, Molecular

l-Cystine bismorpholide (1a) and l-cystine bis(N'-methylpiperazide) (1b) were seven and twenty-four times more effective than l-cystine dimethyl ester (CDME) in increasing the metastable supersaturation range of l-cystine, respectively, effectively inhibiting l-cystine crystallization. This behavior can be attributed to inhibition of crystal growth at microscopic length scale, as revealed by atomic force microscopy. Both 1a and 1b are more stable than CDME, and 1b was effective in vivo in a knockout mouse model of cystinuria.

Topics: Administration, Oral; Amino Acid Transport Systems, Basic; Amino Acid Transport Systems, Neutral; Animals; Cystine; Cystinuria; Diamide; Disease Models, Animal; Male; Mice; Mice, Knockout; Models, Molecular; Molecular Structure