ar-v7

AR AR-V7-IN-1 (Compound 20i) serves as an inhibitor of AR ARV7, demonstrating an IC 50 of 172.85 nM. It effectively inhibits cell growth in the LNCaP and 22RV1 cell lines, with IC 50 values of 4.87 μM and 2.07 μM, respectively. Additionally, it shows potent tumor growth inhibition in a 22RV1 xenograft study. AR AR-V7-IN-1 is useful in studies related to prostate cancer [1].

Ar-V7-IN-1 is a highly potent inhibitor specifically targeting Ar-V7, a splice variant of the androgen receptor exhibiting hormone-independent behavior, and shows promise for researching various indications, notably cancers such as prostate cancer[1].

PROTAC AR AR-V7 degrader-1 (27c) serves as a dual degrader targeting both AR and AR-V7, showcasing DC50 values of 2.67 and 2.64 μM for AR and AR-V7, respectively. It effectively induces apoptosis.

PROTAC AR-V7 degrader-1 (Compound 6) is an orally bioavailable, potent, and selective degrader targeting the androgen receptor (AR) variant V7, achieving degradation with a DC50 of 0.32 µM by directing the VHL E3 ligase to the AR DNA-binding domain (DBD). It demonstrates efficacy in the 22Rv1 cell line expressing AR-V7, with an EC50 of 0.88 µM [1].

VPC-70063 (Thiourea, N-[3,5-bis(trifluoromethyl)phenyl]-N'-(phenylmethyl)-) is an inhibitor of c-Myc-MAX. VPC-70063 exhibits Myc-Max transcriptional activity inhibition of 106% with an IC50 of 8.9 μM and Myc-Max UBE2C downstream pathway inhibition of 94%. VPC-70063 can be used for studies about anticancer.

LX1, an anti-prostate cancer compound, specifically targets the androgen receptor (AR), AR variants, and the steroidogenic enzyme AKR1C3. It inhibits AKR1C3's enzymatic function, decreases the conversion of androstenedione to testosterone, and reduces the expression of both AR and AR-V7, subsequently downregulating their target genes. Additionally, LX1 is effective in overcoming tumor cell resistance to Enzalutamide, and when combined with Enzalutamide, it further suppresses tumor growth.

XYD049 (compound 7d) is a CRBN-type molecular glue targeting GSPT1, with a DC50 of 19 nM, used for researching MYC-driven castration-resistant prostate cancer (CRPC). It effectively inhibits the growth of 22Rv1 cells (IC50 = 7 nM) and exhibits antitumor efficacy in vivo. XYD049 downregulates CRPC-associated oncogenes in 22Rv1 cells, including AR, AR-v7, PSA, and c-Myc. XYD049 comprises a molecular glue linker (black part) NH2-C5-NH-Boc, a CRBN-type E3 ligase ligand (blue part) Thalidomide 4-fluoride, and a target protein ligand (red part) GSPT1 ligand-1, with the E3 ligase ligand + linker forming the conjugate E3 Ligase Ligand-linker Conjugate 158.

VPC-80051 is the first small molecule inhibitor of hnRNP A1 splicing activity by using a computer-aided drug discovery approach.

YT 6-2 is an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, used in the synthesis of AUTOTAC degrader ATC-324. ATC-324 induces the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and also degrades common AR mutants in PCa.

Thailanstatin D, an analogue of Thailanstatin A, inhibits AR-V7 gene splicing by disrupting the interaction between U2AF65 and SAP155, hindering their binding to the polypyrimidine tract situated between the branch point and the 3' splice site. This compound displays potent tumor inhibitory properties in human castration-resistant prostate cancer (CRPC) xenografts, resulting in cellular apoptosis.

Anticancer agent 135 (compound 26h) is a potent androgen receptor (AR) antagonist that blocks AR nuclear translocation and inhibits AR AR-V7 heterodimerization to suppress downstream gene transcription, demonstrating strong efficacy in prostate cancer xenograft models [1].

WCA-814, an androgen receptor (AR) antagonist-Hsp90 inhibitor conjugate, induces degradation of both full-length and AR-V7, exhibiting cytotoxic effects in prostatic cancer cells with half maximal inhibitory concentrations (IC50) of 171.2 nM and 26.5 nM for LNCaP and 22Rv1 cells, respectively [1].

(R)-SKBG-1 is an inhibitor of the RNA-binding protein NONO, effectively downregulating androgen receptor expression by targeting both AR-FL mRNA and AR-V7 mRNA, with inhibition concentration (IC50) values of 3.1 μM and 5.5 μM, respectively [1].

MTX-23, an AR-targeted Proteolysis Targeting Chimera (PROTAC), effectively degrades both AR-V7 and AR-FL, inhibiting the proliferation of CaP cells and inducing apoptosis [1].

YT 6-2-PEG3-C2-NH2 is a conjugate of the autophagy-targeting ligand (ATL) targeting p62 SQSTM1 and an AUTOTAC linker. It is used in the synthesis of the AUTOTAC degrader ATC-324 for the androgen receptor (AR). ATC-324 induces the formation of the AR p62 complex, leading to autophagy-lysosomal degradation of AR. This action reduces nuclear AR levels and downregulates target gene expression of AR and AR-v7, effectively degrading common AR mutants found in prostate cancer (PCa).

SC912 is an AR-V7 inhibitor with an IC50 of 0.36 μM. It directly binds to AR-FL and AR-V7 proteins, preventing their nuclear localization and chromatin binding. SC912 can exert anticancer effects by suppressing cell proliferation, inducing cell cycle arrest, and promoting apoptosis.

BWA-522 is a small molecule, orally available protein-targeting chimera (PROTAC) that potentates the degradation of both full-length androgen receptor (AR-FL) and the AR-V7 splice variant. It specifically antagonizes the N-terminal domain (AR-NTD) of the androgen receptor (Androgen Receptor), prompting apoptosis in prostate cancer (PC) cells. In LNCaP xenograft models, BWA-522 demonstrated tumor growth inhibition (60 mg kg, po; TGI=76%). The compound effectively reduced levels of AR-V7 and AR-FL by 77.3% at 1 μM and 72.0% at 5 μM, respectively, in VCaP and LNCaP cell lines [1].

YT 6-2 analog-1 (compound 2-3) serves as an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, useful in synthesizing the AUTOTAC degrader ATC-324 for the Androgen Receptor (AR). ATC-324 promotes the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It effectively reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and can degrade common AR mutants found in prostate cancer (PCa).

PROTAC AR Degrader-8 (Compound NP18) functions as a PROTAC degrader targeting the androgen receptor (AR) and effectively degrades AR-FL in both 22Rv1 and LNCaP cells with DC50 values of 0.018 μM and 0.14 μM, respectively. It also degrades AR-V7 in 22Rv1 cells with a DC50 of 0.026 μM. Additionally, PROTAC AR Degrader-8 inhibits the proliferation of 22Rv1 and LNCaP cancer cells, exhibiting IC50 values of 0.038 μM and 1.11 μM. It induces cell cycle arrest at the G2 M phase and triggers apoptosis in 22Rv1 cells (apoptosis). Demonstrating anticancer efficacy, PROTAC AR Degrader-8 shows activity in both mouse and zebrafish models. [Pink: ligand for target protein AR ligand-33; Black: linker; Blue: ligand for E3 ligase Cereblon]

VPC-80051 is an hnRNP A1 splicing activity inhibitor that directly interacts with the hnRNP A1 RBD and reduces AR-V7 messenger levels in the 22Rv1 CRPC cell line. VPC-80051 is applicable in prostate cancer research.

SC428 acts as an inhibitor of the androgen receptor (AR), specifically targeting the N-terminal domain of AR. This compound effectively diminishes the transactivation of various AR forms, including AR-V7, ARv567es, full-length AR (AR-FL), and its LBD mutants. Additionally, SC428 significantly inhibits AR-FL nuclear translocation, chromatin binding, and AR-regulated gene transcription under androgen stimulation. In vitro, SC428 suppresses the proliferation of tumor cells. In vivo, it inhibits tumor growth in mice transplanted with 22Rv1 cells by inducing apoptosis.

IPI-9119 is an orally active, selective, and irreversible FASN inhibitor (IC50 = 0.3 nM).

PROTAC AR-NTD antagonist 1 (compound 18) is a small molecule from the protein-targeting chimeras (PROTACs) that selectively targets the N-terminal domain (AR-NTD) of the Androgen Receptor variant AR-V7. By antagonizing AR-NTD, it effectively degrades AR-V7 protein and induces apoptosis in prostate cancer (PC) cells, with degradation efficiencies of 62.2% (1 μM) and 71.1% (5 μM) in VCaP cells [1].