5''N''-Bicalutamide, or 5-azabicalutamide, is a highly potent

nonsteroidal antiandrogen A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like ...

(NSAA) which was discovered in 2016.Pamela, M., Fletterick, R. J., Kuchenbecker, K., & de Jesus Cortez, F. (2016). U.S. Patent Application No. 15/382,942. https://www.google.com/patents/US20170101384 It is a structural modification of

bicalutamide Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical remo ...

differing it from it only by the replacement of a

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...

atom with a

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

atom in one of its

phenyl ring In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...

s. Similarly to bicalutamide, the drug acts as a selective antagonist of the androgen receptor (AR). However, unlike bicalutamide, it is a reversible covalent antagonist and stays bound to the receptor for a far longer amount of time. As a result of this difference, 5''N''-bicalutamide has markedly improved

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

relative to bicalutamide, with approximately 150-fold higher

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for the AR (K_i = 0.15 nM versus 22.3 nM) and about 20-fold greater functional inhibition ( = 15 nM versus 310 nM) of the AR. Future studies of 5''N''-bicalutamide in normal and

mutated In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...

prostate cancer

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s are planned or underway and it is anticipated that ''N''-bicalutamide may be able to overcome resistance to current antiandrogens that are used in the treatment of prostate cancer.

Enzalutamide Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castrat ...

and related second-generation NSAAs like RD-162 and

apalutamide Apalutamide, sold under the brand name Erleada among others, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatme ...

were derived from bicalutamide and as a result are similar to it in

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...

. They have up to about 10-fold higher affinity for the AR than does bicalutamide and hence are comparatively more potent and efficacious antiandrogens. However, their structures are rigidified such that the analogous structural modification that was done with bicalutamide to create 5''N''-bicalutamide could not be used to increase affinity or potency with them. Enzalutamide was described in 2013 as "the emperor of all antiandrogens" and other second-generation NSAAs have similar potency to it, so 5''N''-bicalutamide would appear to be among the most potent AR antagonists to have been developed thus far.

References

Aromatic nitriles Benzosulfones Experimental cancer drugs Hormonal antineoplastic drugs Nonsteroidal antiandrogens Pyridines Tertiary alcohols Trifluoromethyl compounds {{Genito-urinary-drug-stub

See also

References