castration-resistant prostate cancer

Bavdegalutamide (ARV-110) is an oral protein degrader that specifically binds to AR and mediates its degradation. Bavdegalutamide can degrade clinically relevant mutant AR proteins, maintain activity in a high androgen environment, and has an acceptable safety profile.

Luxdegalutamide (ARV-766) is a PROTAC and a protein degrader targeting the androgen receptor, capable of effectively degrading wild-type and drug-resistant mutants including L702H, H875Y, and T878A. With oral bioactivity and cell permeability, this compound is used in castration-resistant prostate cancer research and exhibits significant antitumor activity.

Y06137 is an effective and selective BET inhibitor with a Kd of 81 nM for BRD4(1) bromodomain. Y06137 can be used for research on the treatment of castration-resistant prostate cancer.

MC-1-F2 is a direct FOXC2 inhibitor with anticancer activity, inhibits cancer stem cell (CSC) characteristics, and reduces the invasive ability of castration-resistant prostate cancer (CRPC) cell lines. MC-1-F2 can be used to study prostate cancer.

Bicalutamide (ICI-176334), a synthetic, nonsteroidal antiandrogen, competitively binds to cytosolic androgen receptors in target tissues, thereby inhibiting the receptor binding of androgens.

Cabazitaxel (taxoid XRP6258) is a taxane and antineoplastic agent which is currently used in the therapy of castration-resistant metastatic prostate cancer after failure of docetaxel.

Abiraterone Acetate (CB7630) is an androstene derivative that inhibits STEROID 17-ALPHA-HYDROXYLASE and is used as an ANTINEOPLASTIC AGENT in the treatment of metastatic castration-resistant PROSTATE CANCER.

GDC-2992 is a selective and orally active androgen receptor (AR) degradator that degrades AR (DC50 = 2.7 nM) and inhibits proliferation (IC50 = 9.7 nM) in VCaP cells, making it suitable for studying castration-resistant prostate cancer (CRPC).

LLS30 is an allosteric inhibitor of Galectin-1 (Gal-1). LLS30 inhibits the downstream MEK/ERK signaling pathway and also inhibits Akt phosphorylation. LLS30 exhibits potent proliferation-inhibitory activity against various prostate cancer cell lines.

(S,R,S)-AHPC-Me dihydrochloride, also known as VHL ligand 2 dihydrochloride, is a chemical compound used in the synthesis of ARV-771. ARV-771 is a BET PROTAC degrader that relies on von Hippel-Landau (VHL) E3 ligase and exhibits potent degradation of BET proteins in castration-resistant prostate cancer (CRPC) cells, with a DC50 of less than 1 nM. This compound acts as the VHL ligand, specifically the (S,R,S)-AHPC-based VHL ligand, facilitating the recruitment of von Hippel-Lindau (VHL) protein.

EC1169 is a targeted tubulysin conjugate that utilizes EC1167 as its linker. This compound shows promise in the treatment of recurrent metastatic, castration-resistant prostate cancer (MCRPC)[1].

Compound Z15 (ZNU-IMB-Z15) acts as an antagonist and degrader of the androgen receptor (AR). It inhibits the proliferation of castration-resistant prostate cancer (CRPC) cell lines that are AR-positive and induces apoptosis. Compound Z15 exhibits anticancer activity both in vivo and in vitro.

(+)-JJ-74-138 is a novel non-competitive androgen receptor (AR) antagonist capable of inhibiting enzalutamide-resistant castration-resistant prostate cancer (CRPC).

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.

PSMA-trillium is a PSMA-targeting compound comprising a PSMA-targeting molecule (PSMA binding agent), a Macropa chelator, and a pharmacokinetics-modulating group (PK modulator). It acts as the non-radioactive variant of Actinium-225-PSMA-Trillium (BAY 3563254), boasting enhanced PSMA targeting and pharmacokinetic properties. PSMA-trillium can bind with Ac through either the Macropa chelator or the radioactive isotope Actinium-225. Actinium-225-PSMA-Trillium effectively inhibits metastatic castration-resistant prostate cancer (mCRPC).

(+)-JJ-450 is a non-competitive antagonist that targets the androgen receptor (AR), inhibiting nuclear localization and transcriptional activity of AR under androgen-deprived conditions. In LN95 cells, (+)-JJ-450 is less effective than (-)-JJ-450 at inhibiting prostate-specific antigen (PSA) expression, likely due to its targeting of the AR ligand-binding domain (LBD). The compound works by promoting degradation of unbound AR within the nucleus and reducing AR binding to androgen response elements (AREs), thus inhibiting the transcriptional activity of AR and its splicing variants like ARv7. Additionally, (+)-JJ-450 is applicable for research in castration-resistant prostate cancer (CRPC) that is resistant to Enzalutamide (MDV3100).

JJ-450 is a non-competitive antagonist that targets androgen receptors (AR), capable of inhibiting the transcriptional activity of both wild-type AR and mutant ARF876L. It demonstrates an IC50 of approximately 1-10 μM for suppressing AR transcriptional activity in PC3 cells and selectively binds to AR without competing for the ligand binding domain (LBD) with androgens. JJ-450 functions by inhibiting the nuclear translocation of AR and promoting the degradation of unbound ligand AR within the nucleus, thereby suppressing the transcriptional activity of AR and its splice variants, such as ARF876L. This compound can be utilized in studies of castration-resistant prostate cancer (CRPC) that are resistant to Enzalutamide (MDV3100).

SJL2-1 is a PRMT5 inhibitor with an IC50 value of 1.56 μM. It suppresses the proliferation, migration, and invasion of prostate cancer cells and induces apoptosis while causing cell cycle arrest at the G0/G1 phase. SJL2-1 targets intracellular PRMT5, inhibiting androgen receptor methylation and expression. It is applicable in research on early androgen-sensitive prostate cancer and advanced castration-resistant prostate cancer (CRPC).

(-)-JJ-450 is a non-competitive antagonist targeting the androgen receptor (AR). It is more effective than (+)-JJ-450 in inhibiting androgen-induced AR activity, while (+)-JJ-450 inhibits AR via a mechanism distinct from Enzalutamide (MDV3100), possibly targeting the ligand-binding domain (LBD) of AR. (-)-JJ-450 inhibits transcriptional activity of both wild-type AR and the mutant ARF876L by suppressing AR nuclear translocation and promoting intranuclear degradation of unbound AR. This compound can be utilized in research focusing on castration-resistant prostate cancer (CRPC) that is resistant to Enzalutamide.

LYA914 is an orally active AR/AR-V7 PROTAC degrader. It targets the proteolysis of the androgen receptor's (AR) conserved DNA-binding domain (DBD). LYA914 demonstrates effective antiproliferative activity in Enzalutamide-insensitive or resistant cells and inhibits tumor growth in VCaP/LNCaP tumor mouse models. It is suitable for studying castration-resistant prostate cancer (CRPC).

AR antagonist 17 is a selective, orally active androgen receptor (AR) antagonist with limited ability to cross the blood-brain barrier (IC50 = 0.010 μM). It effectively inhibits AR dimerization and nuclear translocation, demonstrating strong efficacy in various castration-resistant prostate cancer (CRPC) cells. AR antagonist 17 shows excellent effectiveness against various resistant AR mutants. It also suppresses tumor growth without notable toxicity in LNCaP xenograft models. AR antagonist 17 is useful for research in castration-resistant prostate cancer (CRPC).

KI-ARv-03 is a potent and selective ATP-competitive CDK9 inhibitor with an IC50 of 0.15 μM (in the presence of 45 μM ATP), demonstrating over 130-fold selectivity for CDK9 over other CDKs (including CDK1-7). It reduces AR-driven transcription and proliferation in prostate cancer cells and is applicable for research on leukemia, pancreatic cancer, alveolar rhabdomyosarcoma (ARMS), and castration-resistant prostate cancer (CRPC). Additionally, KI-ARv-03 serves as a ligand for target protein for PROTAC and is used in the synthesis of PROTAC KI-CDK9d-32[1][2].

SYY-B029-2 is a potent inhibitor of histone acetyltransferase (HAT) with an IC50 of 1.4 nM. It effectively inhibits the growth of human mantle cell lymphoma (MCL) cell line MAVER-1 and the human castration-resistant prostate cancer cell line LNCaP clone FGC, with IC50 values of 15 nM and 13 nM, respectively.

N-(3-Methylphenyl)anthranilic acid is an inhibitor of aldo-keto reductase 1C3 (AKR1C3) and AKR1C2 with IC50 values of 0.24 μM and 0.38 μM, respectively. It does not inhibit COX-1 or COX-2. This compound can be utilized in research on castration-resistant prostate cancer.