HBK001
HBK001 is an orally active and selective dual GPR119 agonist and DPP-IV inhibitor. HBK001 triggers cAMP production, PKA activation, CREB phosphorylation, glucose-stimulated insulin secretion, plasma incretin elevation, β-cell proliferation, and β-cell function gene up-regulation. HBK001 reduces blood glucose, ameliorates hyperglycemia, improves glucose tolerance, and enhances islet morphology. HBK001 can be used for the research of type 2 diabetes mellitus.
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- CAS 番号: 1942922-78-2
- 分子式: C30H38N10O3
- 分子量:586.69
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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DPP-4 40 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| Vero | IC50 |
46.6 μg/mL
Compound: 21h; HBK001
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Cytotoxicity against African green monkey Vero cells incubated for 48 hrs by MTT assay
Cytotoxicity against African green monkey Vero cells incubated for 48 hrs by MTT assay
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[PMID: 31926470] |
HBK001 potently inhibits DPP-IV with an IC50 of 0.04 μM[1].
HBK001 (10 μM) exhibits no inhibitory activity against DPP-8/9 at 10 μM, demonstrating high selectivity for DPP-IV[1].
HBK001 acts as a GPR119 agonist in HEK293 cells with an EC50 of 1.40 μM and 58% relative activity at 1 μM[1].
HBK001 (30 min) shows low stability in mouse and rat hepatocytes, but favorable stability in human hepatocytes with 101.2% substrate remaining after 30 min incubation[1].
HBK001 (serial dilutions; 48 h) displays low cytotoxicity against Vero cells with an IC50 of 46.6 μg/mL[1].
HBK001 (3.28 nM-10 μM; 24 h) activates GPR119 in transfected HEK293 cells with an EC50 of 0.03 μM[2].
HBK001 (10 μM; 24 h) does not activate GPR40, GLP1R, or GIPR at 10 μM in transfected HEK293 cells, demonstrating selective activation of GPR119 over related GPCRs[2].
HBK001 (1-10 μM) enhances glucose-stimulated insulin secretion in ICR mouse primary islets in vitro in a concentration-dependent manner at 16.7 mM glucose[2].
HBK001 (10 μM) enhances glucose-stimulated insulin secretion in human primary islets from healthy donors[2].
HBK001 (0.1-10 μM) increases intracellular cAMP production in NIT-1 mouse pancreatic β-cells in vitro in a concentration-dependent manner[2].
HBK001 (10 μM) activates transactivation of mouse Ins1 and Ins2 gene promoters in GPR119-transfected HEK293 cells at 10 μM[2].
HBK001 (10 μM; 24 h) upregulates expression of β-cell function-related genes (Nkx6.1, Nkx2.2, Ins1, Ins2) in ICR mouse primary islets[2].
HBK001 (10 μM) enhances glucose-stimulated insulin secretion in KKAy mouse primary islets via an adenylate cyclase-dependent pathway[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:ICR mouse primary islets
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Concentration:10 μM
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Incubation Time:24 h
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Result:Upregulated expression of β-cell function-related genes (Nkx6.1, Nkx2.2, Ins1, Ins2)
HBK001 (5-30 mg/kg; p.o.; single dose) selectively inhibits serum DPP4 activity, increases glucose-stimulated incretin release, and reduces glucose excursion in euglycemic ICR mice, with a glucose-lowering plateau at 30 mg/kg[2].
HBK001 (30 mg/kg; p.o.; daily; 6 weeks) ameliorates hyperglycemia, improves glucose tolerance, enhances insulin secretion, normalizes islet morphology, and up-regulates β-cell function-related genes in spontaneous diabetic KKAy mice via GPR119-dependent signaling, despite only inhibiting ~50% of serum DPP4 activity[2].
HBK001 (30 mg/kg; p.o.; daily; 5 weeks) ameliorates hyperglycemia and improves glucose tolerance in spontaneous diabetic db/db mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR mice (male, 26-27 g)[1]
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Dosage:30 mg/kg
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Administration:p.o.; single dose
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Result:Reduced blood glucose levels after oral glucose loading.
Showed higher area under the oral glucose tolerance test curve (AUCOGTT) than HBK001 hydrochloride (22) group at equivalent molar dose.
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Animal Model:ICR mice (male)[2]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Achieved approximately 50% serum DPP4 inhibition compared to baseline for about 4 hours at 30 mg/kg.
Increased glucose-induced total GLP-1 levels by 41.0% and glucose-induced GIP levels by 40.2% compared to vehicle at 30 mg/kg.
Significantly reduced blood glucose levels 30 minutes after oral glucose loading at doses of 5, 10, 20, and 30 mg/kg, with the area under the curve (AUC) decreased by 17.1%, 21.8%, 24.2%, and 22.8%, respectively, compared to vehicle.
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Animal Model:KKAy mice (female, spontaneous diabetic, fasting blood glucose >180 mg/dl)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 6 weeks
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Result:Significantly decreased fasting blood glucose levels over 6 weeks.
Reduced OGTT AUC by 26.5% compared to vehicle.
Inhibited ~50% of serum DPP4 activity.
Increased first-phase insulin secretion by 4.7-fold compared to vehicle.
Increased glucose infusion rate (GIR) during hyperglycemic clamp.
Increased β-cell area percentage by 17.9% compared to vehicle.
Increased pancreatic CREB phosphorylation.
Up-regulated β-cell function-related genes including NeuroD, Nkx6.1, Nkx2.2, MafA, Ins1, and Ins2 compared to vehicle.
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Animal Model:db/db (BKS.Cg-m+/+ Leprdb/J) mice (female, spontaneous diabetic, fasting blood glucose >180 mg/dl)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 5 weeks
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Result:Significantly decreased fasting blood glucose levels over 5 weeks.
Reduced OGTT AUC by 13.0% compared to vehicle, with effects comparable to linagliptin.
化学情報
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CAS 番号 1942922-78-2
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分子量 586.69
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分子式 C30H38N10O3
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SMILES
CC#CCN1C2=C(N(C(N(C2=O)CCCN3CCN(C4=NC(C5=CC=CC=C5)=NO4)CC3)=O)C)N=C1N6C[C@@H](CCC6)N
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Li G, et al. The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119. Eur J Med Chem. 2020;188:112017. [Content Brief]
[2]. Huan Y, et al. The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. Sci Rep. 2017;7(1):4351. Published 2017 Jun 28. [Content Brief]
Calculators
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