GSK5852 (GSK2485852) is an HCV (hepatitis C virus) NS5B RdRp polymerase inhibitor. GSK5852 inhibits NS5B with IC50 of 50 nM. GSK5852 has anti-viral effect with EC50 of 3.0 nM (GT1a) and 1.7 nM (GT1b) against HCV (hepatitis C virus).

Physicochemical Properties

Molecular Formula	C27H25BF2N2O6S
Molecular Weight	554.3718
Exact Mass	554.149
CAS #	1331942-30-3
PubChem CID	53354790
Appearance	Typically exists as solid at room temperature
Density	1.5±0.1 g/cm3
Index of Refraction	1.670
LogP	3.9
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	8
Heavy Atom Count	39
Complexity	974
Defined Atom Stereocenter Count	0
SMILES	S(C)(N(CC1C=CC(B(O)O)=C(C=1)F)C1=CC2=C(C(C(NC)=O)=C(C3C=CC(=CC=3)F)O2)C=C1C1CC1)(=O)=O
InChi Key	GDSKPIAEYNJODX-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H25BF2N2O6S/c1-31-27(33)25-20-12-19(16-4-5-16)23(13-24(20)38-26(25)17-6-8-18(29)9-7-17)32(39(2,36)37)14-15-3-10-21(28(34)35)22(30)11-15/h3,6-13,16,34-35H,4-5,14H2,1-2H3,(H,31,33)
Chemical Name	[4-[[[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl]-methylsulfonylamino]methyl]-2-fluorophenyl]boronic acid
Synonyms	GSK2485852; GSK 2485852; GSK-2485852
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	One component of HCV is nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase (RdRp), which is utilized to investigate illnesses associated with HCV infection [1]. GSK5852, also known as chemical 87, prevents aggregation by two methods: 1) Stabilizing β-flap in a closed, inactive state to impede the first stage of the RdRp RNA replication cycle; 2) RNA processing channels being disrupted by direct spatial contact[1]. The non-nucleoside NS5B inhibitor GSK5852 inhibits HCV mutations with EC50 values of 1.9 nM (GT1b C316N) and 3.2 nM (GT1a C316Y) [1]. In NS5B resistance mutations that are clinically significant, GSK5852 demonstrates a five-fold reduction in efficacy and good drug resistance [2]. In NS5B, GSK5852 does not show cross-resistance to known resistance mutations [2]. The first stage of the NS5B polymerase cycle is blocked by GSK5852 (Compound 3) (0–10 μM) [3]. When bound to the isolated GT1b 316N protein, GSK5852 (0.6, 10 μM; 0-75 hours) binds slowly and has a dissociation half-life longer than 40 hours [3]. With an IC50 value of 130 nM, GSK5852 (0.6, 10 μM; 15 min) inhibits NS5BΔ21 1b 316N.
Cell Assay	Western Blot Analysis[3] Cell Types: HCV NS5B Tested Concentrations: 0, 0.016, 0.08, 0.4, 2, 10 μM Incubation Duration: Experimental Results: Caused CTP substrate migration (10 μM), pCpG reaction product diminished Dramatically with increasing concentration diminished at doses >2 μM. Indicates that NS5B is prevented from starting.
References	[1]. Small molecule NS5B RdRp non-nucleoside inhibitors for the treatment of HCV infection: A medicinal chemistry perspective. Eur J Med Chem. 2022 Jul 8. 240:114595. [2]. In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2013 Nov;57(11):5216-24. [3]. Discovery of a potent boronic acid derived inhibitor of the HCV RNA-dependent RNA polymerase. J Med Chem. 2014 Mar 13;57(5):1902-13.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) 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). 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) 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). 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8038 mL	9.0192 mL	18.0385 mL
	5 mM	0.3608 mL	1.8038 mL	3.6077 mL
	10 mM	0.1804 mL	0.9019 mL	1.8038 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.