Table 1.
Drugs and correlated mechanisms in CRPC.
| Drugs | Drug Source | Clinical Development Stage of the Drug | Mechanism | Reference |
|---|---|---|---|---|
| C86 JG98 Uercetin VER155008 |
Compound medicine | Preclinical studies | Inhibit HSP40 or HSP70 and promote AR-V7 degradation. | Liu et al. (2018) [86] Kazuaki Kita et al. (2017) [98] Michael A Moses et al. (2018) [83] |
| KRIBB3 | Compound medicine | Preclinical studies | Inhibit HSP27 and promote AR-V7 degradation | Ilker Kiliccioglu et al. (2019) [75] |
| Niclosamide | Compound medicine | It is an anthelminthic drug approved by FDA in 1982 and is in preclinical research in the treatment of CRPC. | Inhibition of AR-V7 transcriptional activity and down-regulation of AR-V7 protein expression. | Liu et al. (2014, 2017) [84,99] Navid Sobhani et al. (2018) [100] |
| ARVib | Compound medicine | Preclinical studies | Promoting AR/AR-V7 protein degradation through HSP70/STUB1. | Liu et al. (2021) [87] |
| Bruceantin | Compound medicine | The drug was used in phase I and phase II clinical trials for the treatment of B16 melanoma, colon 38, L1210, and P388 leukemia, but no objective tumor regression was observed, so the clinical trial was terminated. At present, the research on PCa removal is limited to preclinical research. | Inhibition of HSP90 promotes degradation of AR/AR-V7. | Sue Jin Moon et al. (2021) [88] |
| Nobiletin | Natural medicine | Preclinical studies | Inducing proteasomal degradation of AR-V7. | Liu et al. (2021) [92] |
| Huaier Extract | Natural medicine | Preclinical studies | Down-regulation of USP14 and promotes proteasomal degradation of AR/AR-V7. | Liu et al. (2021) [95] |
| Rut | Natural medicine | Preclinical studies | Targeting GRP78-dependent AR-V7 protein degradation. | Liao et al. (2020) [96] |
| MTX23 | Compound medicine | Preclinical studies | Binds to the DNA binding domain of AR and VHL E3 ubiquitin ligase to promote the degradation of AR/AR-V7. | Geun Taek Lee et al. (2021) [97] |
| Indometacin | Compound medicine | It is a nonsteroidal anti-inflammatory drug approved by FDA in 2014 and is in preclinical research in the treatment of CRPC. | Target AKR1C3 and promote AR-V7 degradation. | Liu et al. (2019) [101] Wang et al. (2020) [102] |
| CX4945 | Compound medicine | Preclinical studies | Target CK2 and down-regulated AR-V7 at both mRNA and protein levels. | Deng et al. (2017) [103] |
| Leelamine | Natural medicine | Preclinical studies | Down-regulation of AR/AR-Vs protein expression | Krishna B Singh et al. (2018) [104] |
| Bortezomib | Compound medicine | Approved by FDA in 2003 for the treatment of MM and MCL, its role in CRPC is in preclinical research stage. | Target NF-κB and down-regulation of AR-Vs protein expression. | R Jin et al. (2015) [105] |
| NaAsO2 | Compound medicine | Preclinical studies | Down-regulated nuclear translocation and protein expression of AR/AR-Vs | Kim et al. (2017) [106] |
| ASC-J9 | Compound medicine | Preclinical studies | Promote AR/AR-V7 degradation. | Shinichi Yamashita et al. (2012) [107] |
| Luteolin | Natural medicine | Preclinical studies | Down-regulated the expression level of AR-V7. | Aya Naiki-Ito et al. (2020) [108] |
| Indisulam | Compound medicine | Indisulam is an aryl sulfonamide drug with selective anticancer activity, its relationship with ENZ is in pre-clinical research stage. | Down-regulated AR-V7 mRNA expression level. | James E Melnyk et al. (2020) [109] |
Abbreviations: CRPC: Castration-resistant prostate cancer; FDA: Food and drug administration; AR: Androgen receptor; AR-V: Androgen receptor splice variant; HSP: Heat shock protein; USP: ubiquitin specific peptidase; CK2: Casein kinase 2; MM: Multiple myeloma; MCL: Mantle cell lymphoma.