Table 1: List of bioactive molecules/compounds targeting androgen and AR related mechanisms.

Molecule/compound Nature of the molecule/compound Targets Mode of action References
Niphatenone B Glycerol ether initially isolated from
themarine sponge Niphates digitalis		 Androgen Receptor N-Terminal Domain Inhibits transactivation of AR NTD, blocks endogenous expression of
AR-regulated genes PSA and Kallikrein-2, covalent binding to AR AF-1 peptide.		 Banuelos, et al. [4]
Sintokamide A Natural compound isolated and purified
from the marine sponge Dysidea sp.		 AF-1 of Androgen receptor Inhibits transactivation of AR NTD, attenuate transcriptional activities of both full-length AR and constitutively active AR splice variants AR-V567es, repressed androgen-induced levels of transcripts of FL-AR-regulated genes (KLK3/PSA, KLK2, TMPRSS2, NKX3.1, FKBP5, and SLC1A1). Banuelos, et al. [6]
Isosilybin A Flavolignan; one of the 7 components of Silymarin Androgen receptor signaling Decreases AR and PSA level in prostate cancer cells. Deep, et al. [36]
Thiostrepton and Siomycin A Thiazole antibiotics AR signaling in neurons Reduces expression of FOXM1 transcription factor and
ß-catenin, both required for localization and expression of AR.		 Otto-Duessel, et al. [37]
Emodin Anthraquinone compound obtained from 50%
ethanolic extract of Polygonum multiflorum Thunb. (Family: Polygonaceae)		 5α-reductase Inhibits 5α-reductase enzyme activity. Cho, et al. [31]
6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl) nicotinamide-26(DIMN-26) 6-(3,4-Dihydro-1H-isoquinoline-2-yl)-N-(6-methoxypyridine-2-yl) nicotinamide-26 AR signaling Inhibits Dihydrotestosterone (DHT) production, induce cell growth and proliferation, suppresses DHT-induced transcriptional activity and nuclear translocation of AR, binds to LBD (Ligand Binding Domain) of AR, reduced mRNA levels of PSA, AR, Ste20-related Protein Proline/Alanine-Rich Kinase (SPAK), Beta-2-Microglobulin (B2M), and Selenoprotein P1(SEPP1). Choi, et al. [33]
Tocopheryl Quinone (TQ) Oxidation product of alpha-tocopherol Androgen receptor in prostate cancer cells Decreases gene expression of TM4SF1, KLK2, FOXA1 and PSA. Fajardo, et al. [38]
1,4-Substituted Triazoles Non-steroidal antiandrogen Androgen receptor in prostate cancer cells Reduces the level of PSA. Ferroni, et al. [39]
Darolutamide (ODM-20) Non-steroidal antiandrogen Androgen receptor of CRPC cells Reduces serum PSA in CRPC and blocks nuclear translocation of AR. Fizazi, et al. [40]
Zyflamend Polyherbal preparation consisting of the supercritical CO2 fluid extracts of 10 different herbs Androgen receptor in CRPC model Reduces mRNA levels of AR and PSA. Huang, et al. [41]
M-MeI (1- (pyridine-2-yl)-3-(m-tolyl) imidazo [1,5-a]pyridine),
a derivative of HIMP (3-phenyl-1-(pyridine-2-yl) imidazo[1,5-a]pyridine)		 Androgen receptor of CRPC Methyl group on the para position of the benzene ring in M-MeI suppress AR activity, decreases levels of PSA and p66Shc (a protein regulated by androgens). Ingersoll, et al. [42]
Minnelide Water soluble pro-drug of triptolide, a diterpene triepoxide isolated from a Chinese herb, Tripterygium wilfordii Androgen receptor and its splice variants of CRPC Induces apoptosis in androgen dependent and CRPC cells, inhibits AR transcription and downstream AR targets such as PSA and NKX3.1, prevents translocation of Sp1 to the nucleus (a transcription factor of AR). Isharwal, et al. [43]
Decursin Ethanol extract of herbal formula containing Korean Angelica Gigas Nakai (AGN) root and 9 Oriental herbs Antiandrogen and androgen receptor Suppression of PSA mRNA and protein, inhibits androgen-stimulated AR translocation to the nucleus, down-regulates AR protein abundance without interfering AR transcription. Jiang, et al. [10]
Cyclopropane (1S,2R)-27 Thioether isostere Nuclear androgen receptor Reduction in PSA activity. Johnson, et al. [14]
Lambertianic acid Isolated Pinus koraiensis Siebold and Zucc (Family: Pinaceae) Androgen receptor Attenuates expression of AR and PSA. Lee, et al. [3]
D4A A converted form of abiraterone Androgen receptor Inhibits CYP17A1, 3αHSD and SRD5A, required for DHT synthesis, AR antagonist, Inhibits DHT-induced AR chromatin occupancy on the PSA, TMPRSS2 and FKBP5 regulatory elements on chromatin. Li, et al. [1]
Cryptotan shinone Active extract of Salvia miltiorrhiza Bunge (Danshen), chemical name: (R)-1,2,6,7,8,9-Hexahydro-1,6,6-trimethyl- phenanthro (1,2-b) furan-10,11-dione Androgen receptor in prostate cancer Inhibits DHT-mediated AR transactivation, inhibits transcription of AR target genes (PSA, TMPRSS2, and TMEPA1), Inhibits AR N/C-Dimerization and formation of AR-coregulatory complex, blocked E2 or Adiol-mediated AR activity. Xu, et al. [44]
AR1-558 Decoys of AR NTD residues 1-558 Androgen regulated genes Reduces the expression of androgen-regulated genes HMGCR, KLK2, KLK3/PSA, MAF, RHOU, and SAT1, blocks AR-ARE interactions. Myung, et al. [45]
Galeterone (ongoing clinical trials) 3α-(hydroxy)-17-(1H-benzimidazole-1-yl) androstane-5,16-dione Androgen receptor CYP17 inhibition, AR antagonist and AR degrader. Bastos & Antonarakis [46]
Compound 6m 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivative Androgen receptor Decreases androgen-mediated transcription of ARE-mRNA in PSA, TMPRSS2. Saravanan, et al. [47]
NBBS (N-butylbenzene sulphonamide) Dichloromethane extract from stem bark of Pygeum africanum Androgen hormone Inhibits AR mediated transactivation and androgen hormone induction. Schleich, et al. [48]
Isobavachin, Glabranin, Anthocyanin and Eriosemation (via structure based docking studies) Phytochemicals Androgen receptor AR antagonists. Singh, et al. [49]
Flutamide Non-steroidal drug Androgen receptor in salivary duct carcinoma Blocks DHT activity, inhibits invasion of DHT mediated cells. Kamata, et al. [50]
CID 70128824, CID 70127147, and CID 70126881 7α-substituted dihydrotestosterones by linear Quantitative Structure-Activity Relationship (QSAR) model (in-silico screening) Androgen receptor antagonists or antiandrogens Wang, et al. [51]
Metformin Anti-diabetic drug, originally from Galega officinalis (French lilac) Androgen receptor Reduces mRNA and protein levels of AR. Whitburn, et al. [13]
Diterpenoids T1 and its analogues T2 and T3 Furanoditerpenoid spongia-13(16), -14-dien-19-oic acid Androgen receptor Inhibits androgen-dependent proliferation and AR transcriptional activity, competes with androgen binding to LBD of AR and blocks essential N/C interactions. Yang, et al. [15]
Combined Androgen Blockade (CAB); immediate switch from Bicalutamide to Flutamide - Prostate Specific Antigen (PSA) Decreases the levels of PSA. Yokomizo, et al. [52]
Acetyl-11-Keto-α-Boswellic Acid(AKBA) Acetyl-11-keto-b-boswellic acid isolated from the gum-resin of Boswellia carterii Androgen receptor in prostate cancer Decrease DHT induced AR expression at both mRNA and protein levels, interruption of Sp1 binding activity, suppression of androgen induction of PSA promoter. Yuan, et al. [53]
6-Bromoindirubin-3-Oxime(6BIO) 6-bromo-indirubin-30-oxime via small molecule high throughput screening Androgen receptor and its signaling in prostate cancer Down-regulates AR-V7 levels, a drug-resistance-related AR splice variant, enhanced ASO (Antisense oligonucleotides) function, represses AR expression by inhibition of two main Glycogen Synthase Kinase 3 (GSK-3) isoforms, GSK-3a and GSK-3b. Zhang, et al. [54]