HIV and HBV

Tenofovir amibufenamide (TMF; HS-10234) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF)[1].
HS-10234 is a novel prodrug of tenofovir developed to increase anti-viral potency and to reduce systemic toxicities[2].

[1]. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther. 2021 Nov;54(9):1134-1149.

[2]. Randomised clinical trial: safety, efficacy and pharmacokinetics of HS-10234 versus tenofovir for the treatment of chronic hepatitis B infection. Aliment Pharmacol Ther. 2021 Jan;53(2):243-252.

Objective: To compare the efficacy and safety of temozolomide (TMF) and tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) over 48 weeks. [1] Methods: We conducted a randomized, double-blind, non-inferiority study at 49 research centers in China. CHB patients were randomized 2:1 to either the TMF group (25 mg) or the TDF group (300 mg) and received matched placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA below 20 IU/mL at week 48. We also assessed safety, particularly for bone, kidney, and metabolic abnormalities. [1] Results: A total of 1002 eligible patients were randomized. The baseline characteristics of the two groups were balanced. All analysis sets met the non-inferiority criteria after a median of 48 weeks of treatment. In the HBeAg-positive population, 50.2% of patients receiving TMF achieved HBV DNA levels below 20 IU/mL, compared to 53.7% of patients receiving TDF. In the HBeAg-negative population, 88.9% and 87.8% of patients in the TMF and TDF groups, respectively, achieved HBV DNA levels below 20 IU/mL. Patients receiving TMF showed significantly smaller decreases in bone mineral density in the hip (P < 0.001) and spine (P < 0.001) compared to the TDF group, and also showed smaller increases in serum creatinine at week 48 (P < 0.05). Other safety outcomes were similar between the two groups. [1] Conclusion: TMF is non-inferior to TDF in terms of anti-HBV efficacy and has better bone and kidney safety. (NCT03903796).[1]

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Objective: To evaluate the tolerability, pharmacokinetics and antiviral efficacy of HS-10234 in patients with chronic hepatitis B (CHB). Methods: Untreated non-cirrhotic CHB patients were randomly assigned to three groups (n = 12 per group) to receive 10 mg, 25 mg or 40 mg HS-10234 or 300 mg tenofovir disoproxil fumarate (TDF) once daily for 28 days. [2]
Results: Among the 36 enrolled subjects, 33.3% were hepatitis B e antigen negative, and the mean hepatitis B virus (HBV) DNA level was 6.32-7.42 log10 IU/mL. No nephrotoxicity or serious adverse events were observed; all adverse events were mild or moderate and nonspecific. After 28 days of treatment, the mean reduction in serum HBV DNA in patients treated with 10 mg, 25 mg, or 40 mg HS-10234 was -2.70, -2.89, -2.72, and -3.04 log10 IU/mL, respectively, while the mean reduction in serum HBV DNA in patients treated with 300 mg TDF was -2.70, -2.89, -2.72, and -3.04 log10 IU/mL, respectively. The pharmacokinetics of HS-10234 and its metabolite TFV showed a linear dose-proportional relationship. Compared with the TDF group, the HS-10234 group had higher concentrations of active TFV-DP in peripheral blood mononuclear cells (approximately 2 to 11 times) and lower concentrations of TFV in plasma (approximately 4.5 to 25 times). [2] Conclusion: HS-10234 was well tolerated during a 4-week course of treatment. TDF and HS-10234 were comparable in their efficacy in inhibiting HBV replication. It is recommended that patients with chronic hepatitis B (CHB) take 10-25 mg of HS-10234 daily. (China Drug Trial Registration No.: CTR20161077) [2]

C22H31N6O5P

490.492505311966

490.209

C, 53.87; H, 6.37; N, 17.13; O, 16.31; P, 6.31

1571076-26-0

(1R)-Tenofovir amibufenamide;1571076-15-7;(R,1R)-Tenofovir amibufenamide;1571076-37-3

118214142

Typically exists as Off-white to light yellow solids at room temperature

2.1

2

10

12

34

720

2

C[C@H](CN1C=NC2=C(N=CN=C21)N)OC[P@](=O)(NC(C)(C)C(=O)OC(C)C)OC3=CC=CC=C3

ORHSFGJQGPUCRR-JTJFVBHCSA-N

InChI=1S/C22H31N6O5P/c1-15(2)32-21(29)22(4,5)27-34(30,33-17-9-7-6-8-10-17)14-31-16(3)11-28-13-26-18-19(23)24-12-25-20(18)28/h6-10,12-13,15-16H,11,14H2,1-5H3,(H,27,30)(H2,23,24,25)/t16-,34-/m1/s1

propan-2-yl 2-[[[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-phenoxyphosphoryl]amino]-2-methylpropanoate

UNII-SGK6176ZDO; Tenofovir amibufenamide; SGK6176ZDO; Tenofovir amibufenamide [INN]; 1571076-26-0; Alanine, N-((S)-(((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-2-methyl-, 1-methylethyl ester; (R,1R)-Tenofovir amibufenamide; propan-2-yl 2-[[[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-phenoxyphosphoryl]amino]-2-methylpropanoate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~200 mg/mL (~407.76 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)