INX 08189
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 529117

CAS#: 1234490-83-5

Description: INX 08189, also known as BMS 986094, is an RNA-directed RNA polymerase (NS5B) inhibitor potentially for the treatment of HCV infection.


Chemical Structure

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INX 08189
CAS# 1234490-83-5

Theoretical Analysis

MedKoo Cat#: 529117
Name: INX 08189
CAS#: 1234490-83-5
Chemical Formula: C30H39N6O9P
Exact Mass: 658.25
Molecular Weight: 658.649
Elemental Analysis: C, 54.71; H, 5.97; N, 12.76; O, 21.86; P, 4.70

Price and Availability

Size Price Availability Quantity
5mg USD 350 2 Weeks
25mg USD 950 2 Weeks
Bulk inquiry

Synonym: INX-189; INX-08189; BMS-986094; INX189; INX08189; BMS986094; INX 189; INX 08189; BMS 986094

IUPAC/Chemical Name: neopentyl ((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphoryl)-L-alaninate

InChi Key: YFXGICNMLCGLHJ-RSKRLRQZSA-N

InChi Code: InChI=1S/C30H39N6O9P/c1-17(26(38)42-15-29(2,3)4)35-46(40,45-20-13-9-11-18-10-7-8-12-19(18)20)43-14-21-23(37)30(5,39)27(44-21)36-16-32-22-24(36)33-28(31)34-25(22)41-6/h7-13,16-17,21,23,27,37,39H,14-15H2,1-6H3,(H,35,40)(H2,31,33,34)/t17-,21+,23+,27+,30+,46?/m0/s1

SMILES Code: C[C@H](NP(OC1=C2C=CC=CC2=CC=C1)(OC[C@H]3O[C@@H](N4C=NC5=C(OC)N=C(N)N=C45)[C@](C)(O)[C@@H]3O)=O)C(OCC(C)(C)C)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: BMS-986094 (INX-08189) is a potent inhibitor of hepatitis C virus (HCV) replication, with an EC50 of 35 nM at 24 h in Huh-7 cells. BMS-986094 is a phosphoramidate prodrug of 6-O-methyl-2’-C-methyl guanosine. BMS-986094 can be used for the research of chronic HCV infection.
In vitro activity: BMS-986094 showed marked cytotoxicity in all human cell lines and primary cells tested. After 5-day treatments with BMS-986094, cardiomyocytes showed the most profound sensitivity to cytotoxicity among the primary cells tested, with a CC50 of 0.68 ± 0.32 μM (mean ± standard deviation), almost equivalent to that of puromycin (CC50 of 0.33 ± 0.05 μM). Reference: Antimicrob Agents Chemother. 2015 Nov 23;60(2):806-17. https://pubmed.ncbi.nlm.nih.gov/26596942/
In vivo activity: These data suggest that INX-08189 is efficiently extracted from the portal circulation by the monkey liver following oral administration, which results in the formation of the active HCV polymerase inhibitor 2′-C-MeGTP in liver tissue. Reference: Antimicrob Agents Chemother. 2011 May;55(5):1843-51. https://pubmed.ncbi.nlm.nih.gov/21357300/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 157.9 239.78
Ethanol 65.9 99.99

Preparing Stock Solutions

The following data is based on the product molecular weight 658.65 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Feng JY, Xu Y, Barauskas O, Perry JK, Ahmadyar S, Stepan G, Yu H, Babusis D, Park Y, McCutcheon K, Perron M, Schultz BE, Sakowicz R, Ray AS. Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus. Antimicrob Agents Chemother. 2015 Nov 23;60(2):806-17. doi: 10.1128/AAC.01922-15. PMID: 26596942; PMCID: PMC4750701. 2. Vernachio JH, Bleiman B, Bryant KD, Chamberlain S, Hunley D, Hutchins J, Ames B, Gorovits E, Ganguly B, Hall A, Kolykhalov A, Liu Y, Muhammad J, Raja N, Walters CR, Wang J, Williams K, Patti JM, Henson G, Madela K, Aljarah M, Gilles A, McGuigan C. INX-08189, a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob Agents Chemother. 2011 May;55(5):1843-51. doi: 10.1128/AAC.01335-10. Epub 2011 Feb 28. PMID: 21357300; PMCID: PMC3088254.
In vitro protocol: 1. Feng JY, Xu Y, Barauskas O, Perry JK, Ahmadyar S, Stepan G, Yu H, Babusis D, Park Y, McCutcheon K, Perron M, Schultz BE, Sakowicz R, Ray AS. Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus. Antimicrob Agents Chemother. 2015 Nov 23;60(2):806-17. doi: 10.1128/AAC.01922-15. PMID: 26596942; PMCID: PMC4750701.
In vivo protocol: 1. Vernachio JH, Bleiman B, Bryant KD, Chamberlain S, Hunley D, Hutchins J, Ames B, Gorovits E, Ganguly B, Hall A, Kolykhalov A, Liu Y, Muhammad J, Raja N, Walters CR, Wang J, Williams K, Patti JM, Henson G, Madela K, Aljarah M, Gilles A, McGuigan C. INX-08189, a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob Agents Chemother. 2011 May;55(5):1843-51. doi: 10.1128/AAC.01335-10. Epub 2011 Feb 28. PMID: 21357300; PMCID: PMC3088254.

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1: McGuigan C, Madela K, Aljarah M, Gilles A, Brancale A, Zonta N, Chamberlain S, Vernachio J, Hutchins J, Hall A, Ames B, Gorovits E, Ganguly B, Kolykhalov A, Wang J, Muhammad J, Patti JM, Henson G. Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4850-4. doi: 10.1016/j.bmcl.2010.06.094. PubMed PMID: 20637609.

2: Vernachio JH, Bleiman B, Bryant KD, Chamberlain S, Hunley D, Hutchins J, Ames B, Gorovits E, Ganguly B, Hall A, Kolykhalov A, Liu Y, Muhammad J, Raja N, Walters CR, Wang J, Williams K, Patti JM, Henson G, Madela K, Aljarah M, Gilles A, McGuigan C. INX-08189, a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob Agents Chemother. 2011 May;55(5):1843-51. doi: 10.1128/AAC.01335-10. PubMed PMID: 21357300; PubMed Central PMCID: PMC3088254.

3: Yeo KL, Chen YL, Xu HY, Dong H, Wang QY, Yokokawa F, Shi PY. Synergistic suppression of dengue virus replication using a combination of nucleoside analogs and nucleoside synthesis inhibitors. Antimicrob Agents Chemother. 2015 Apr;59(4):2086-93. doi: 10.1128/AAC.04779-14. PubMed PMID: 25624323; PubMed Central PMCID: PMC4356831.

4: Gentile I, Buonomo AR, Zappulo E, Borgia G. Discontinued drugs in 2012 - 2013: hepatitis C virus infection. Expert Opin Investig Drugs. 2015 Feb;24(2):239-51. doi: 10.1517/13543784.2015.982274. PubMed PMID: 25384989.

5: Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Zennou V, Otto MJ, Furman PA. Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA. J Virol. 2011 Dec;85(23):12334-42. doi: 10.1128/JVI.05639-11. PubMed PMID: 21957306; PubMed Central PMCID: PMC3209386.

6: Feng JY, Xu Y, Barauskas O, Perry JK, Ahmadyar S, Stepan G, Yu H, Babusis D, Park Y, McCutcheon K, Perron M, Schultz BE, Sakowicz R, Ray AS. Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus. Antimicrob Agents Chemother. 2015 Nov 23;60(2):806-17. doi: 10.1128/AAC.01922-15. PubMed PMID: 26596942; PubMed Central PMCID: PMC4750701.

7: Liu A, Lute J, Gu H, Wang B, Trouba KJ, Arnold ME, Aubry AF, Wang J. Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Sep 1;1000:29-40. doi: 10.1016/j.jchromb.2015.07.006. PubMed PMID: 26209768.

8: Ahmad T, Yin P, Saffitz J, Pockros PJ, Lalezari J, Shiffman M, Freilich B, Zamparo J, Brown K, Dimitrova D, Kumar M, Manion D, Heath-Chiozzi M, Wolf R, Hughes E, Muir AJ, Hernandez AF. Cardiac dysfunction associated with a nucleotide polymerase inhibitor for treatment of hepatitis C. Hepatology. 2015 Aug;62(2):409-16. doi: 10.1002/hep.27488. PubMed PMID: 25251156.

9: Furman PA, Murakami E, Niu C, Lam AM, Espiritu C, Bansal S, Bao H, Tolstykh T, Micolochick Steuer H, Keilman M, Zennou V, Bourne N, Veselenak RL, Chang W, Ross BS, Du J, Otto MJ, Sofia MJ. Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661. Antiviral Res. 2011 Aug;91(2):120-32. doi: 10.1016/j.antiviral.2011.05.003. PubMed PMID: 21600932; PubMed Central PMCID: PMC3135787.