Lersivirine | CAS#473921-12-9 | NNRT inhibitor

MedKoo Cat#: 319834 | Name: Lersivirine

Description:

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

Lersivirine, also known as UK-453061, is a novel second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) under development for HIV infection therapy. It binds reverse transcriptase in a distinct way leading to a unique resistance profile. In February 2013, ViiV Healthcare announced a stop of the development program investigating lersivirine.

Chemical Structure

Lersivirine

CAS#473921-12-9

Theoretical Analysis

MedKoo Cat#: 319834

Name: Lersivirine

CAS#: 473921-12-9

Chemical Formula: C17H18N4O2

Exact Mass: 310.1430

Molecular Weight: 310.36

Elemental Analysis: C, 65.79; H, 5.85; N, 18.05; O, 10.31

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,450.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,950.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Synonym

UK-453061; UK453061; UK 453061; UK-453,061; UK453,061; UK 453,061;Lersivirine

IUPAC/Chemical Name

5-((3,5-diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl)oxy)isophthalonitrile

InChi Key

MCPUZZJBAHRIPO-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H18N4O2/c1-3-15-17(16(4-2)21(20-15)5-6-22)23-14-8-12(10-18)7-13(9-14)11-19/h7-9,22H,3-6H2,1-2H3

SMILES Code

N#CC1=CC(OC2=C(CC)N(CCO)N=C2CC)=CC(C#N)=C1

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, not in water

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

Product Data

Instruction

View handling instruction

Biological target:

Lersivirine (UK-453061) is potent and selective non-nucleoside reverse transcription inhibitor (NNRTI; IC50=119 nM) with excellent efficacy against NNRTI-resistant viruses.

In vitro activity:

The emerging candidate, lersivirine (UK-453,061), binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC(50)s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets. Altogether lersivirine is a highly potent and selective NNRTI, with excellent efficacy against NNRTI-resistant viruses. Reference: Antimicrob Agents Chemother. 2010 Oct;54(10):4451-63. https://pubmed.ncbi.nlm.nih.gov/20660667/

In vivo activity:

Administration of lersivirine, a nonnucleotide reverse transcriptase inhibitor, daily by oral gavage to Sprague-Dawley rats for up to 2 yr was associated with decreased survival, decreased body weights, and an increase in neoplasms and related proliferative lesions in the liver, thyroid, kidney, and urinary bladder. Reference: Toxicol Pathol. 2015 Apr;43(3):354-65. https://pubmed.ncbi.nlm.nih.gov/25122632/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	96.66
	DMSO	47.3	152.51
	Ethanol	36.0	116.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 310.36 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.

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. Corbau R, Mori J, Phillips C, Fishburn L, Martin A, Mowbray C, Panton W, Smith-Burchnell C, Thornberry A, Ringrose H, Knöchel T, Irving S, Westby M, Wood A, Perros M. Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2010 Oct;54(10):4451-63. doi: 10.1128/AAC.01455-09. Epub 2010 Jul 26. PMID: 20660667; PMCID: PMC2944613. 2. Allan G, Davis J, Dickins M, Gardner I, Jenkins T, Jones H, Webster R, Westgate H. Pre-clinical pharmacokinetics of UK-453,061, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), and use of in silico physiologically based prediction tools to predict the oral pharmacokinetics of UK-453,061 in man. Xenobiotica. 2008 Jun;38(6):620-40. doi: 10.1080/00498250802069088. PMID: 18570162. 3. Nambiar PR, Morton D, Dochterman LW, Houle C, Thomford PJ, Fate G, Bailey SA, Finch GL. Two-year carcinogenicity study in rats with a nonnucleoside reverse transcriptase inhibitor. Toxicol Pathol. 2015 Apr;43(3):354-65. doi: 10.1177/0192623314544381. Epub 2014 Aug 13. PMID: 25122632. 4. Houle CD, Finch GL, Mauthe RJ, Potter DM, Walisser JA, Gardner IB, DeWit RH. Effects of lersivirine on canine and rodent thyroid function. Toxicol Pathol. 2014 Jul;42(5):897-912. doi: 10.1177/0192623313503516. Epub 2013 Oct 16. PMID: 24135463.

In vitro protocol:

In vivo protocol:

1. Nambiar PR, Morton D, Dochterman LW, Houle C, Thomford PJ, Fate G, Bailey SA, Finch GL. Two-year carcinogenicity study in rats with a nonnucleoside reverse transcriptase inhibitor. Toxicol Pathol. 2015 Apr;43(3):354-65. doi: 10.1177/0192623314544381. Epub 2014 Aug 13. PMID: 25122632. 2. Houle CD, Finch GL, Mauthe RJ, Potter DM, Walisser JA, Gardner IB, DeWit RH. Effects of lersivirine on canine and rodent thyroid function. Toxicol Pathol. 2014 Jul;42(5):897-912. doi: 10.1177/0192623313503516. Epub 2013 Oct 16. PMID: 24135463.

1: DeJesus E, Fätkenheuer G, Orrell C, Wang C, Jones J, Craig C, Tawadrous M, Heera J. Efficacy and safety of lersivirine versus etravirine for the treatment of HIV-1 infection in patients with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) use and evidence of NNRTI resistance: a randomized phase 2B trial. HIV Clin Trials. 2014 Sep-Oct;15(5):209-17. doi: 10.1310/hct1505-209. PubMed PMID: 25350959. 2: Houle CD, Finch GL, Mauthe RJ, Potter DM, Walisser JA, Gardner IB, DeWit RH. Effects of lersivirine on canine and rodent thyroid function. Toxicol Pathol. 2014 Jul;42(5):897-912. doi: 10.1177/0192623313503516. Epub 2013 Oct 16. PubMed PMID: 24135463. 3: Platten M, Fätkenheuer G. Lersivirine - a new drug for HIV infection therapy. Expert Opin Investig Drugs. 2013 Dec;22(12):1687-94. doi: 10.1517/13543784.2013.846325. Epub 2013 Oct 16. Review. PubMed PMID: 24128277. 4: Vourvahis M, Davis J, Langdon G, Layton G, Fang J, Choo HW, Hansson AG, Tawadrous M. Pharmacokinetic interactions between lersivirine and zidovudine, tenofovir disoproxil fumarate/emtricitabine and abacavir/lamivudine. Antivir Ther. 2013;18(6):745-54. doi: 10.3851/IMP2566. Epub 2013 Apr 4. PubMed PMID: 23558061. 5: Vernazza P, Wang C, Pozniak A, Weil E, Pulik P, Cooper DA, Kaplan R, Lazzarin A, Valdez H, Goodrich J, Mori J, Craig C, Tawadrous M. Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment-naive HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial. J Acquir Immune Defic Syndr. 2013 Feb 1;62(2):171-9. doi: 10.1097/QAI.0b013e31827a2ba2.. PubMed PMID: 23328090. 6: Vourvahis M, Wang R, Gruener DM, Bruce RD, Haider S, Tawadrous M. Effect of lersivirine co-administration on pharmacokinetics of methadone in healthy volunteers. Drug Alcohol Depend. 2012 Nov 1;126(1-2):183-8. doi: 10.1016/j.drugalcdep.2012.05.009. Epub 2012 Jun 8. PubMed PMID: 22682979. 7: Vourvahis M, Davis J, Wang R, Layton G, Choo HW, Chong CL, Tawadrous M. Effect of rifampin and rifabutin on the pharmacokinetics of lersivirine and effect of lersivirine on the pharmacokinetics of rifabutin and 25-O-desacetyl-rifabutin in healthy subjects. Antimicrob Agents Chemother. 2012 Aug;56(8):4303-9. doi: 10.1128/AAC.06282-11. Epub 2012 May 29. PubMed PMID: 22644026; PubMed Central PMCID: PMC3421562. 8: Kar P, Knecht V. Energetics of mutation-induced changes in potency of lersivirine against HIV-1 reverse transcriptase. J Phys Chem B. 2012 Jun 7;116(22):6269-78. doi: 10.1021/jp300818c. Epub 2012 May 22. PubMed PMID: 22574920. 9: Davis J, Langdon G, Layton G, Chong CL, Ndongo MN, Vourvahis M. The effect of lersivirine, a next-generation NNRTI, on the pharmacokinetics of midazolam and oral contraceptives in healthy subjects. Eur J Clin Pharmacol. 2012 Nov;68(11):1567-72. doi: 10.1007/s00228-012-1287-5. Epub 2012 Apr 22. PubMed PMID: 22527351. 10: Vourvahis M, Langdon G, Layton G, Labadie RR, Choo HW, Ndongo MN, Davis J. The pharmacokinetics of lersivirine (UK-453,061) and HIV-1 protease inhibitor coadministration in healthy subjects. J Acquir Immune Defic Syndr. 2012 May 1;60(1):24-32. doi: 10.1097/QAI.0b013e31824c4186. PubMed PMID: 22517413. 11: Campion SN, Bowman CJ, Cappon GD, Harrison A, Finch GL, Hurtt ME. Developmental toxicity of lersivirine in rabbits when administered throughout organogenesis and when limited to sensitive windows of axial skeletal development. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):250-61. doi: 10.1002/bdrb.21014. Epub 2012 Apr 11. PubMed PMID: 22495820. 12: Cappon GD, Bowman CJ, Campion SN, Chmielewski G, Hurtt ME, Finch GL, Lewis EM. Developmental toxicity study of lersivirine in mice. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):225-30. doi: 10.1002/bdrb.21008. Epub 2012 Mar 22. PubMed PMID: 22447726. 13: Vourvahis M, Wang R, Ndongo MN, O'Gorman M, Tawadrous M. No effect of a single supratherapeutic dose of lersivirine, a next-generation nonnucleoside reverse transcriptase inhibitor, on corrected QT interval in healthy subjects. Antimicrob Agents Chemother. 2012 May;56(5):2408-13. doi: 10.1128/AAC.05194-11. Epub 2012 Feb 27. PubMed PMID: 22371898; PubMed Central PMCID: PMC3346613. 14: Vourvahis M, Langdon G, Labadie RR, Layton G, Ndongo MN, Banerjee S, Davis J. Pharmacokinetic effects of coadministration of lersivirine with raltegravir or maraviroc in healthy subjects. Antimicrob Agents Chemother. 2012 Feb;56(2):887-92. doi: 10.1128/AAC.00572-11. Epub 2011 Nov 28. PubMed PMID: 22123705; PubMed Central PMCID: PMC3264271. 15: Langdon G, Davis J, Layton G, Chong CL, Weissgerber G, Vourvahis M. Effects of ketoconazole and valproic acid on the pharmacokinetics of the next generation NNRTI, lersivirine (UK-453,061), in healthy adult subjects. Br J Clin Pharmacol. 2012 May;73(5):768-75. doi: 10.1111/j.1365-2125.2011.04136.x. PubMed PMID: 22040521; PubMed Central PMCID: PMC3403204. 16: Jones LH, Allan G, Corbau R, Middleton DS, Mowbray CE, Newman SD, Phillips C, Webster R, Westby M. Comparison of the non-nucleoside reverse transcriptase inhibitor lersivirine with its pyrazole and imidazole isomers. Chem Biol Drug Des. 2011 May;77(5):393-7. doi: 10.1111/j.1747-0285.2011.01113.x. Epub 2011 Mar 29. PubMed PMID: 21352504. 17: Davis J, Hackman F, Ndongo MN, Choo H, Lewis D, Tawadrous M, Goodrich J, Langdon G. Safety and tolerability of lersivirine, a nonnucleoside reverse transcriptase inhibitor, during a 28-day, randomized, placebo-controlled, Phase I clinical study in healthy male volunteers. Clin Ther. 2010 Oct;32(11):1889-95. doi: 10.1016/j.clinthera.2010.10.007. PubMed PMID: 21095483. 18: Corbau R, Mori J, Phillips C, Fishburn L, Martin A, Mowbray C, Panton W, Smith-Burchnell C, Thornberry A, Ringrose H, Knöchel T, Irving S, Westby M, Wood A, Perros M. Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2010 Oct;54(10):4451-63. doi: 10.1128/AAC.01455-09. Epub 2010 Jul 26. PubMed PMID: 20660667; PubMed Central PMCID: PMC2944613. 19: Vourvahis M, Banerjee S, LaBadie R, Gore D, Mayer H. Lack of a clinically relevant effect of an antacid on the pharmacokinetics of lersivirine. Antimicrob Agents Chemother. 2010 May;54(5):2209-11. doi: 10.1128/AAC.01110-09. Epub 2010 Feb 16. PubMed PMID: 20160047; PubMed Central PMCID: PMC2863683. 20: Vourvahis M, Gleave M, Nedderman AN, Hyland R, Gardner I, Howard M, Kempshall S, Collins C, LaBadie R. Excretion and metabolism of lersivirine (5-{[3,5-diethyl-1-(2-hydroxyethyl)(3,5-14C2)-1H-pyrazol-4-yl]oxy}benzene-1,3-dic arbonitrile), a next-generation non-nucleoside reverse transcriptase inhibitor, after administration of [14C]Lersivirine to healthy volunteers. Drug Metab Dispos. 2010 May;38(5):789-800. doi: 10.1124/dmd.109.031252. Epub 2010 Feb 2. PubMed PMID: 20124396.