AZD 9977

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

AZD9977 是一种新型、一流、选择性口服盐皮质激素受体 (MR) 调节剂，pKi 为 7.5，对 GR、PR 和 AR 几乎没有亲和力 (pIC50<5.5)。

AZD9977 is a novel, first-in-class, selective and oral mineralocorticoid receptor (MR) modulator with pKi of 7.5, shows little to no affitnity for GR, PR and AR (pIC50<5.5); dose dependently reduces albuminuria and improves kidney histopathology similar to eplerenone in db/db uni-nephrectomised mice and uni-nephrectomised rats, does not affect urinary Na+/K+ ratio.Diabetes Phase 1 Clinical(In Vitro):Balcinrenone (AZD9977) and eplerenone activities on MR, GR, PR and AR in binding assays. The observed pKi of MR, GR, and PR are 7.5, 5.4 and 4.6, respectively.Functional interaction of Balcinrenone with MR is characterized in a reporter gene assay where the full-length MR drives a luciferase reporter gene in U2-OS cells. Balcinrenone antagonizes aldosterone-activated MR with an IC50 of 0.28 μM. Whereas eplerenone is a full antagonist, Balcinrenone suppresses only 69% of the MR activity in this assay.Species selective potencies of Balcinrenone are established in reporter gene assays using the MR LBDs from human, mouse or rat. The corresponding IC50 values are 0.37 μM, 0.08 μM and 0.08μM, respectively. (In Vivo):Balcinrenone (AZD9977) (oral administration; 10-100 mg/kg; 4 weeks) dose dependently reduces the UACR compared to vehicle in uni-nephrectomised male Sprague Dawley rats administered aldosterone and fed a high-salt diet. Balcinrenone is as efficacious as full MR antagonists on renal protection, despite the partial antagonism observed in in vitro assays.Balcinrenone (oral administration; 100 mg/kg; co-administration with enalapril) stops further disease progression and reduces the urine albumin excretion (UAE) compared to vehicle treatment. Co-administration of enalapril has an apparent additive effect on UAE reduction, although this reduction is not statistically significant.

Balcinrenone (AZD9977) and eplerenone activities on MR, GR, PR and AR in binding assays. The observed pKi?of MR, GR, and PR are 7.5, 5.4 and 4.6, respectively.Functional interaction of Balcinrenone with MR is characterized in a reporter gene assay where the full-length MR drives a luciferase reporter gene in U2-OS cells. Balcinrenone antagonizes aldosterone-activated MR with an IC50 of 0.28 μM. Whereas eplerenone is a full antagonist, Balcinrenone suppresses only 69% of the MR activity in this assay.Species selective potencies of Balcinrenone are established in reporter gene assays using the MR LBDs from human, mouse or rat. The corresponding IC50 values are 0.37 μM, 0.08 μM and 0.08μM, respectively.

Balcinrenone (AZD9977) (oral administration; 10-100 mg/kg; 4 weeks) dose dependently reduces the UACR compared to vehicle in uni-nephrectomised male Sprague Dawley rats administered aldosterone and fed a high-salt diet. Balcinrenone is as efficacious as full MR antagonists on renal protection, despite the partial antagonism observed in?in vitro?assays.Balcinrenone (oral administration; 100 mg/kg; co-administration with enalapril) stops further disease progression and reduces the urine albumin excretion (UAE) compared to vehicle treatment. Co-administration of enalapril has an apparent additive effect on UAE reduction, although this reduction is not statistically significant. Animal Model:Uni-nephrectomised male Sprague Dawley rats administered aldosterone and fed a high-salt diet with AZD9977 Dosage:10, 30 and 100 mg/kg Administration:Oral administration; 10-100 mg/kg; 4 weeks Result:Improved kidney function and histology in animal models of CKD.Animal Model:Db/db mice uni-nephrectomised at 8 weeks of age are treated from age 18w to age 22w Dosage:100 mg/kg Administration:Oral administration; 100 mg/kg; co-administration with enalapril Result:Reduced albuminuria in diabetic kidney disease.Co-administration of enalapril with AZD9977 had an additive effect on renal pathology scoring.

AZD9977

Nuclear Receptor/Transcription Factor

MLR

MLR

Metabolic Disease

Diabetes

1850385-64-6

399.378

C20H18FN3O5

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (625.99 mM)

CNC(=O)CC1COC2=C(N1C(=O)C3=CC4=C(C=C3)OCC(=O)N4)C=CC(=C2)F

(S)-2-(7-fluoro-4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl)-N-methylacetamide

(-20℃)

With Ice Pack

≥ 2 years