ar protein

AZD3514 is a potent and oral androgen receptor downregulator with Ki of 2.2 μM and has ability of reducing AR protein expression.Phase 1.

Luxdegalutamide (ARV-766) is a novel, potent, and orally bioavailable proteolytic targeting chimera (PROTAC) protein degrader that degrades not only wild-type AR but also clinically relevant AR LBD mutants, including the most prevalent AR L702H, H875Y, and T878A mutations.

Androgen receptor antagonist 1 is an orally available full antagonist of the androgen receptor (AR), with an IC50 value of 59 nM, demonstrating high potency against AR signaling. Androgen receptor antagonist 1 can further be employed in the synthesis of PROTAC AR degraders, which induce targeted protein degradation, achieving 24% and 47% AR protein reduction in LNCaP cells at concentrations of 1 μM and 10 μM, respectively, thereby offering significant utility in prostate cancer research.

Higenamine hydrochloride (norcoclaurine HCl) has been demonstrated to be a β2 adrenoreceptor agonist. Adrenergic receptors, or adrenoceptors, belong to the class of G protein–coupled receptors, and are the most prominent receptors in the adipose membrane, besides also being expressed in skeletal muscle tissue.

AR antagonist 1 is a potent antagonist of the androgen receptor. It binds to E3 ligase ligands with weak binding affinities to VHL protein in the synthesis of PROTAC ARD-266.

Netarsudil Dihydrochloride (AR-13324 Dihydrochloride) is an inhibitor of Rho-related protein kinase (ROCK) and norepinephrine transporter (NET) and is effective in reducing intraocular pressure (IOP).

Netarsudil mesylate (AR-13324 mesylate) is a Rho-related protein kinase inhibitor used to study glaucoma and hypertension.

VHL Ligand 8, a VHL ligand essential for synthesizing ARD-266, acts as a highly potent VHL E3 ligase-based androgen receptor (AR) PROTAC degrader. It efficiently facilitates the degradation of AR protein in AR-positive prostate cancer cell lines LNCaP, VCaP, and 22Rv1, exhibiting DC50 values ranging from 0.2-1 nM [1].

ar-Turmerone ((+)-ar-Turmerone) is a major bioactive compound of the herb Curcuma longa with anti-tumorigenesis and anti-inflammatory activities[1][2][3]. It positively modulates murine DCs, induces NSC proliferation, and constitutes a promising therapeutic agent for various neurologic disorders[4][5]. It also activates apoptotic proteins in human lymphoma U937 cells[3].

Boc-Pip-alkyne-Ph-COOH, a PROTAC linker characterized by its alkyl/ether composition, plays a crucial role in synthesizing PROTACs including ARD-266. This compound demonstrates significant efficacy in promoting the degradation of androgen receptor (AR) protein across AR-positive prostate cancer cell lines such as LNCaP, VCaP, and 22Rv1, showcasing DC50 values ranging from 0.2-1 nM[1].

AR ligand-31 is a PROTAC target protein ligand used in synthesizing PROTACAR Degrader-5.

AR ligand-37 is a PROTAC target protein ligand utilized in the synthesis of BMS-986365.

AR ligand-30 serves as the target protein ligand for PROTAC Bavdegalutamide, utilized in prostate cancer research.

E3 Ligase Ligand 42 is a ligand for E3 ubiquitin ligases. It can be conjugated to target protein ligands via a linker, facilitating the synthesis of PROTACAR Degrader-6. PROTACs induce the ubiquitination and degradation of oncogenic proteins.

AR ligand-29 serves as the target protein ligand for PROTACVinclozolinM2-2204, utilized in cancer research.

AR ligand-33 is a ligand for the androgen receptor (AR), and it can be used as a target protein ligand for the synthesis of PROTAC AR Degrader-8.

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]

PROTAC AR Degrader-9 (Compound c6) is a PROTAC-based degrader specifically targeting the androgen receptor. It effectively degrades the androgen receptor in human dermal papilla cells (HDPC) with a DC50 of 262.38 nM. Additionally, this compound enhances the expression of paracrine factors, such as TGF-β1 and β-catenin, thereby promoting hair regeneration in mouse models. [Pink: ligand for target protein AR ligand-38; Black: linker; Blue: ligand for E3 ligase Cereblon]

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.

PROTACAR Degrader-10 is a protein degrader targeting androgen receptors (AR) with a DC50 value of ≤100 nM, and can be used in prostate cancer research.

AR ligand-39 is an orally active and selective androgen receptor (AR) antagonist, functioning as a ligand for target protein in PROTAC. It is utilized in the synthesis of PROTAC AR Degrader-10.

AR antagonist 14 serves as a ligand for the target protein in PROTAC applications. It can be coupled with VH 101-amide-piperidine-Pip-alkyne to synthesize the PROTAC degrader [ARD-69].

AR antagonist 11 (Compound c2) is a selective androgen receptor antagonist with an IC50 of 0.019 μM. It is also effective against the ARF877L/T878A mutant (IC50: 1.03 μM). Additionally, AR antagonist 11 inhibits LNCaP cell proliferation and decreases PSA protein expression (IC50: 0.54 μM). This compound is applicable in prostate cancer (PCa) research.

LO-4-25 is a covalent degrader targeting the androgen receptor (AR) and its splice variant AR-V7. It covalently binds to the E3 ubiquitin ligase CUL4 DCAF16, facilitating the ubiquitination of both AR and AR-V7, which are then recognized and degraded by the proteasome, leading to reduced protein levels of AR and AR-V7 in cells. LO-4-25 is promising for research on androgen-independent prostate cancer.