| ln Vitro |
HBK001 effectively inhibits DPP-IV with an IC50 value of 0.04 μM[1]. HBK001 (10 μM) showed no inhibitory activity against DPP-8/9, indicating that it is highly selective for DPP-IV[1]. HBK001 was used as a GPR119 agonist in HEK293 cells with an EC50 value of 1.40 μM and a relative activity of 58% at a concentration of 1 μM[1]. HBK001 (30 min) showed poor stability in mouse and rat hepatocytes, but good stability in human hepatocytes, with 101.2% of the substrate remaining after 30 min of incubation[1]. HBK001 (serial dilution; 48 h) showed low cytotoxicity to Vero cells with an IC50 value of 46.6 μg/mL[1]. HBK001 (3.28 nM–10 μM; 24 h) activated GPR119 in transfected HEK293 cells at an EC50 of 0.03 μM[2]. HBK001 (10 μM; 24 h) did not activate GPR40, GLP1R, or GIPR in transfected HEK293 cells, indicating that its selective activation of GPR119 was superior to other related GPCRs[2]. HBK001 (1–10 μM) enhanced glucose-stimulated insulin secretion (16.7 mM glucose) in primary islets of ICR mice in vitro in a concentration-dependent manner[2]. HBK001 (10 μM) enhanced glucose-stimulated insulin secretion in primary islets of healthy donors[2]. HBK001 (0.1–10 μM) increased cAMP production in cultured NIT-1 mouse islet β cells in vitro in a concentration-dependent manner[2]. HBK001 (10 μM) can activate the transcription of mouse Ins1 and Ins2 gene promoters in GPR119-transfected HEK293 cells [2]. HBK001 (10 μM; 24 h) can upregulate the expression of genes related to β-cell function (Nkx6.1, Nkx2.2, Ins1, Ins2) in primary pancreatic islets of ICR mice [2]. HBK001 (10 μM) can enhance glucose-stimulated insulin secretion in primary pancreatic islets of KKAy mice through an adenylate cyclase-dependent pathway [2].
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| ln Vivo |
HBK001 (30 mg/kg; orally; single dose) showed hypoglycemic activity in normoglycemic ICR mice at a single oral dose of 30 mg/kg[1]. HBK001 (5-30 mg/kg; orally; single dose) selectively inhibited serum DPP4 activity, increased glucose-stimulated incretin release, and reduced glycemic fluctuations in normoglycemic ICR mice, reaching a hypoglycemic plateau at a dose of 30 mg/kg[2]. HBK001 (30 mg/kg; orally; once daily; for 6 weeks) improved hyperglycemia, increased glucose tolerance, enhanced insulin secretion, normalized islet morphology, and upregulated β-cell function-related genes in spontaneously diabetic KKAy mice through the GPR119-dependent signaling pathway, although it only inhibited about 50% of serum DPP4 activity[2]. HBK001 (30 mg/kg; orally; daily; for 5 weeks) improved hyperglycemia and glucose tolerance in spontaneously diabetic db/db mice[2].
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| Cell Assay |
Real-time quantitative PCR[2]
Cell Types: ICR mouse primary pancreatic islet cells Tested Concentrations: 10 μM Incubation Duration: 24 h Experimental Results: Upregulation of expression of β-cell function-related genes (Nkx6.1, Nkx2.2, Ins1, Ins2) |
| Animal Protocol |
Animal/Disease Models:ICR mice (male, 26-27 g) [1]
Doses: 30 mg/kg Route of Administration: Oral; Single dose Experimental Results: Blood glucose levels decreased after oral glucose loading. The area under the curve (AUCOGTT) of the oral glucose tolerance test was higher compared with the equimolar dose of HBK001 hydrochloride (22). Animal/Disease Models:ICR Mice (Male) [2] Doses: 5 mg/kg; 10 mg/kg; 20 mg/kg; 30 mg/kg Route of Administration: Oral; Single Dosage Experimental Results: At a dose of 30 mg/kg, the serum DPP4 inhibition rate decreased by approximately 50% from baseline, lasting for approximately 4 hours. At a dose of 30 mg/kg, the glucose-induced total GLP-1 level increased by 41.0% compared to the solvent group, and the glucose-induced GIP level increased by 40.2%. 30 minutes after oral glucose loading, at doses of 5, 10, 20, and 30 mg/kg, blood glucose levels decreased significantly, with the area under the curve (AUC) decreasing by 17.1%, 21.8%, 24.2%, and 22.8% respectively compared to the carrier group. Animal/Disease Models:KKAy mice (female, spontaneously diabetic, fasting blood glucose >180 mg/dl)[2] Doses: 30 mg/kg Route of Administration: Oral; daily; 6 weeks Experimental Results: Fasting blood glucose levels were significantly reduced over 6 weeks. The area under the curve (AUC) of the oral glucose tolerance test (OGTT) was reduced by 26.5% compared with the control group. Serum DPP4 activity was inhibited by approximately 50%. First-phase insulin secretion was increased by 4.7 times compared with the control group. Glucose infusion rate (GIR) was increased during the hyperglycemic clamp test. The percentage of β-cell area was increased by 17.9% compared with the control group. Pancreatic CREB phosphorylation was increased. Compared to the vector, β-cell function-related genes (including NeuroD, Nkx6.1, Nkx2.2, MafA, Ins1, and Ins2) were upregulated. Animal/Disease Models:db/db (BKS.Cg-m+/+ Leprdb/J) mice (female, spontaneously diabetic, fasting blood glucose >180 mg/dl) [2] Doses: 30 mg/kg Route of Administration: Oral; daily; 5 weeks Experimental Results: Fasting blood glucose levels were significantly reduced over 5 weeks. Compared with the solvent, the OGTT AUC was reduced by 13.0%, which was comparable to that of linagliptin. |
| References |
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| CAS # |
1942922-78-2
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| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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