Description
HE-3235 is a synthetic adrenal hormone, an androstanediol analog, that acts as an androgen receptor antagonist. In an androgen receptor-dependent manner, it downregulates anti-apoptotic genes, while increasing the expression of pro-apoptotic genes, thus stimulating apoptosis. HE-3235 has been shown to inhibit androstenediol-dependent LNCaP cell tumor growth both in vitro (IC50 = 6 nM) and in xenograft models in vivo.
Uses
Apoptone, synthetic analogue of 3β-androstanediol, is an orally bioavailable anticancer agent. Apoptone is active in rodent models of prostate and breast cancer[1]. Apoptone is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
in vitro
in lncap cells expressing a mutated androgen receptor, he3235 significantly inhibited activity for aed-stimulated lncap proliferation. this inhibitory activity is accompanied by an increase in the number of apoptotic cells [1].
in vivo
animal studies have confirmed the cytoreductive activity of he3235 on lncap tumours. the results suggest that this compound may be of clinical use in castration-resistant prostate cancer. in castrated male mice implanted subcutaneously with lucap35v cap xenografts, treatment with he3235 significantly prolonged the tumor doubling time of lucap35v, decreased androgen receptor expression, and lowered levels of intratumoral testosterone by 89% and dihydrotestosterone by 63% in both the presence and the absence of aed. he3235 inhibited tumor growth in the bone environment. he3235 inhibited the growth of subcutaneous crpc as well as crpc in the bone environment. he3235 exhibited a wide range of effects, including alteration of androgen receptor signaling and reductions in levels of intratumoral androgens. weights of tumored tibiae of he3235-treated animals were lower than those of control [3].
References
[1] trauger r, corey e, bell d, et al. inhibition of androstenediol-dependent lncap tumour growth by 17α-ethynyl-5α-androstane-3α, 17β-diol (he3235)[j]. british journal of cancer, 2009, 100(7): 1068-1072.
[2] gelmann e p. molecular biology of the androgen receptor[j]. journal of clinical oncology, 2002, 20(13): 3001-3015.[3 gelmann e p. molecular biology of the androgen receptor[j]. journal of clinical oncology, 2002, 20(13): 3001-3015.] koreckij t d, trauger r j, montgomery r b, et al. he3235 inhibits growth of castration-resistant prostate cancer[j]. neoplasia, 2009, 11(11): 1216in22-1225in23.
