Binding of centchroman—a nonsteroidal antifertility agent to human plasma proteins

Abstract

Centchroman, a non-steroidal antifertility agent showed a low affinity (Kd = 13.19 X 10(-6) M) and nonsaturable binding to human plasma. Centchroman did not compete either with sex hormone binding globulin or corticosteroid binding globulin. Polyacrylamide gel electrophoresis and temperature dependent binding characteristics revealed that the protein responsible for centchroman binding to human plasma resembles albumin.

Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone‐related clinical disorders

“…0.68) in rat, rabbit, guinea pig, rhesus monkey 135,136 and human, 137,138 with K d value of 13.12 Â 10 À5 , 13.7 Â 10 À5 , 8.51 Â 10 À5 , 11.87 Â 10 À5 , and 13.19 Â 10 À6 M, respectively. SDS-PAGE analysis after incubation with puri®ed human serum albumin shows a single radioactive peak (rf.…”

“…0.68), identical to that of plasma bound 14 C-centchroman complex. 136,137 It does not compete with cortisol, estradiol, progesterone, testosterone, dihydrotestosterone or nonsteroidal estrogen agonist diethylstilbestrol or antagonists tamoxifen and nafoxidene and is unlikely to displace steroids from speci®c steroid binding plasma proteins. 137 Its binding characteristics are not altered by incubation at 4, 45 or 60 C. 136,137 It possesses high lipophilicity (log P 7.41).…”

Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens

“…In human plasma, centchroman is protein bound in a non-saturable manner, most likely to albumin, and shows no affinity to SHBG and corticoid binding globulin. However, the degree of binding has not been described (SRIVASTAVA et al 1984).…”

Anti-Cancer Potential of a Novel SERM Ormeloxifene

“…This drug demonstrates low binding affinity to plasma albumin (Kd value of 13.90× 10 −6 ) and does not interact with steroids like testosterone, cortisol, estradiol and progesterone [13–16]. It is therefore predicted to not interfere with the binding of steroids to specific steroid binding plasma proteins [17–19]. Additionally, while ormeloxifene is a selective modulator of estrogen receptor(s), it has been shown to neither compete with nonsteroidal estrogen agonists like diethylstilbestrol nor with estrogen antagonists like tamoxifen or nafoxidene [19].…”

“…It is therefore predicted to not interfere with the binding of steroids to specific steroid binding plasma proteins [17–19]. Additionally, while ormeloxifene is a selective modulator of estrogen receptor(s), it has been shown to neither compete with nonsteroidal estrogen agonists like diethylstilbestrol nor with estrogen antagonists like tamoxifen or nafoxidene [19]. …”