Provided is a novel compound having a selective activating effect on ERβ. The present invention provides a compound represented by the following formula (1) wherein R.sup.1 represents a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 6 carbon atoms and optionally substituted with a halogen atom, a 5-membered nitrogen-containing heteroaryl group, a 4- to 6-membered cyclic amino group, an alkanoylamino group having 2 to 6 carbon atoms and optionally substituted with a halogen atom, a 1-trifluoromethyl-1-hydroxymethyl group, or a 1-methylpropyl group; R.sup.2 to R.sup.5 are the same or different and each represent a hydrogen atom or a fluorine atom; and R.sup.6 represents a hydrogen atom or an alkanoyl group having 2 to 5 carbon atoms, or a salt thereof.

##STR00001##

Provided is a novel compound having a selective activating effect on ERβ. The present invention provides a compound represented by the following formula (1) wherein R.sup.1 represents a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 6 carbon atoms and optionally substituted with a halogen atom, a 5-membered nitrogen-containing heteroaryl group, a 4- to 6-membered cyclic amino group, an alkanoylamino group having 2 to 6 carbon atoms and optionally substituted with a halogen atom, a 1-trifluoromethyl-1-hydroxymethyl group, or a 1-methylpropyl group; R.sup.2 to R.sup.5 are the same or different and each represent a hydrogen atom or a fluorine atom; and R.sup.6 represents a hydrogen atom or an alkanoyl group having 2 to 5 carbon atoms, or a salt thereof.

##STR00001##

Provided herein are methods for treating small round cell tumor(s) by administering anti-androgen receptor therapy to a subject. The anti-androgen receptor therapy may comprise an AR antisense oligonucleotide and may be administered in combination with an additional anti-cancer agent.

Indazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole-3-carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedys disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedys disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Embodiments of the present invention provide a pharmaceutical intervention in the neonatal to infantile ruminants that inhibits the activation of the HPG axis, growth of the testis and inhibits testicular production of testosterone, which prevent the development of aggressive behavior in the maturing males and the presence of male-specific odor in the meat. The invention comprises treatment with an estrogen or a combination of an estrogen and an androgen in the newborn males using extended drug delivery methods, with a defined duration of no more than 1-4 months or infantile period of growth, for the purpose of inhibiting the production of testosterone and the accumulation of male-specific odor. The drug delivery component may consist of biocompatible-/biodegradable polymers in the form of pellets, microspheres, or gels, or in solvents or solutions (hereafter, drug complex). The invention embodies neonatal/infantile period treatment with a drug complex consisting of a hormone-based compound configured to inhibit development and function of hypothalamic Kisspeptin neurons, pituitary release of luteinizing hormone and postnatal development of the testis through the use of sustained but temporary release of the compounds into the body of an animal once the drug-carrier has been injected or implanted therein.

Embodiments of the present invention provide a pharmaceutical intervention in the neonatal to infantile ruminants that inhibits the activation of the HPG axis, growth of the testis and inhibits testicular production of testosterone, which prevent the development of aggressive behavior in the maturing males and the presence of male-specific odor in the meat. The invention comprises treatment with an estrogen or a combination of an estrogen and an androgen in the newborn males using extended drug delivery methods, with a defined duration of no more than 1-4 months or infantile period of growth, for the purpose of inhibiting the production of testosterone and the accumulation of male-specific odor. The drug delivery component may consist of biocompatible-/biodegradable polymers in the form of pellets, microspheres, or gels, or in solvents or solutions (hereafter, drug complex). The invention embodies neonatal/infantile period treatment with a drug complex consisting of a hormone-based compound configured to inhibit development and function of hypothalamic Kisspeptin neurons, pituitary release of luteinizing hormone and postnatal development of the testis through the use of sustained but temporary release of the compounds into the body of an animal once the drug-carrier has been injected or implanted therein.

The present invention refers to a new enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17α,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone-17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate.

Interfering nucleic acids and methods of their use in treat prostate cancers, such as aggressive prostate cancers. The nucleic acids may be, for example, short interfering RNA (siRNA), short hairpinRNA (shRNA), antisense RNA, antisense DNA, Chimeric Antisense DNA/RNA, and microRNA (miRNA) oligonucleotides. The oligonucleotide has a seed sequence that is complementary to a sequence of either a gene or an mRNA encoding an androgen receptor (AR) coregulator or a fragment thereof having AR coregulator activity. The nucleic acid compound may have a non-natural modification in the oligonucleotide, and/or an organic moiety conjugated to the oligonucleotide. The oligonucleotide has inhibitory activity against the expression or biological activity of the AR coregulator.