ARD-2128

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ARD-2128 是一种高效、口服生物可利用的 PROTAC 雄激素受体 (AR) 降解剂。 ARD-2128有效降低AR蛋白，抑制肿瘤组织中AR调节基因，抑制肿瘤生长，且无毒性迹象。

ARD-2128 is a highly potent, orally bioavailable PROTAC androgen receptor (AR) degrader. ARD-2128 effectively reduces AR protein, suppresses AR-regulated genes in tumor tissues, and inhibits growth of tumor without signs of toxicity. ARD-2128 has the potential for the research of the prostate cancer.(In Vitro):ARD-2128 is highly potent and effective in the inhibition of cell growth in the VCaP cell line and LNCaP cell line with the IC 50 values of 4 nM and 5 nM, respectively . ARD-2128 (1, 10, 100, and 1000 nM; 24 hours) effectively reduces the AR protein level by >50% at 1 nM and achieves the AR degradation of >90% at 10, 100, and 1000 nM, respectively, in VCaP cell . Cell Viability Assay Cell Line: VCaP cell Concentration: 1, 10, 100, and 1000 nM Incubation Time: 24 hours Result: Reduces the AR protein level and achieves the AR degradation.(In Vivo):ARD-2128 (20 mg/kg; p.o.; once) is effective in reducing the level of AR protein in mice after 24 hours . ARD-2128 (10-40 mg/kg; p.o.; daily for 21 days) shows antitumor activity in the VCaP xenograft model in mice . ARD-2128 (5mg/kg; p.o.) treatment shows the C max , AUC 0-t and t 1/2 values of 1304 ng/mL, 22361 ng h/mL and 18.8 hours, respectively . Animal Model: SCID mice Dosage: 20 mg/kg Administration: Oral Result: Reducing the level of AR protein in mice after 24 hours. Animal Model: SCID mice Dosage: 10, 20, and 40 mg/kg Administration: P.o.; daily for 21 days Result: Inhibits tumor growth by 46, 69, and 63%, respectively. Animal Model: Male ICR Mice Dosage: 5 mg/kg Administration: P.o. (Pharmacokinetic Analysis) Result: The C max , AUC 0-t and t 1/2 were 1304 ng/mL, 22361 ng h/mL and 18.8 hours, respectively.

Cell Viability Assay Cell Line:VCaP cell Concentration:1, 10, 100, and 1000 nM Incubation Time:24 hours Result:Reduces the AR protein level and achieves the AR degradation.

Animal Model:SCID mice Dosage:20 mg/kg Administration:Oral Result:Reducing the level of AR protein in mice after 24 hours.Animal Model:SCID mice Dosage:10, 20, and 40 mg/kg Administration:P.o.; daily for 21 days Result:Inhibits tumor growth by 46, 69, and 63%, respectively.Animal Model:Male ICR Mice Dosage:5 mg/kg Administration:P.o. (Pharmacokinetic Analysis)Result:The Cmax, AUC0-tand t1/2 were 1304 ng/mL, 22361 ng h/mL and 18.8 hours, respectively.

——

Endocrinology/Hormones

Androgen Receptor (AR)

TNIK

——

——

2222111-87-5

820.38

C45H50ClN7O6

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (121.90 mM)

CC(C)([C@H](C1(C)C)NC(c(cc2)ccc2N2CCN(CC(CC3)CCN3c(cc3)cc(C(N4C(CCC(N5)=O)C5=O)=O)c3C4=O)CC2)=O)[C@H]1Oc(cc1)cc(Cl)c1C#N

——

(-20℃)

With Ice Pack

≥ 2 years