Leflunomide | CAS#75706-12-6

MedKoo Cat#: 318090 | Name: Leflunomide

Featured

Description:

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

Leflunomide (original brand name Arava) is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Chemical Structure

Leflunomide

CAS#75706-12-6

Theoretical Analysis

MedKoo Cat#: 318090

Name: Leflunomide

CAS#: 75706-12-6

Chemical Formula: C12H9F3N2O2

Exact Mass: 270.0616

Molecular Weight: 270.21

Elemental Analysis: C, 53.34; H, 3.36; F, 21.09; N, 10.37; O, 11.84

Price and Availability

Size	Price	Availability	Quantity
200mg	USD 250.00
500mg	USD 450.00
1g	USD 750.00

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

Leflunomide, Arava, Leflunomidum, HWA-486

IUPAC/Chemical Name

5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide

InChi Key

VHOGYURTWQBHIL-UHFFFAOYSA-N

InChi Code

InChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18)

SMILES Code

O=C(C1=C(C)ON=C1)NC2=CC=C(C(F)(F)F)C=C2

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:

Leflunomide is a pyrimidine synthesis inhibitor, inhibiting dihydroorotate dehydrogenase (DHODH).

In vitro activity:

This study demonstrates that PTEN-deficient prostate cancer cell lines are susceptible to inhibition of de novo pyrimidine synthesis by leflunomide. Tumor growth inhibition was observed in vitro and in vivo following leflunomide treatment, and is likely due to an overwhelming accumulation of DNA damage. Reference: Prostate Cancer Prostatic Dis. 2020 Dec;23(4):718-723. https://pubmed.ncbi.nlm.nih.gov/32661432/

In vivo activity:

The results showed that AlCl3 disrupted learning and memory parameters in rats and increased amyloid-β plaque deposition and neurofibrillary tangle aggregation. Moreover, AlCl3 administration markedly elevated acetylcholinesterase activity, nuclear factor-kappa β, tumor necrosis factor-α, and interleukin-1 beta, and marked degenerative changes in the pyramidal neurons. However, administration of leflunomide alone or with rivastigmine in AlCl3-induced AD rats restored most of the behavioral, biochemical, and histological parameters triggered by AlCl3 in rats. These findings suggest that leflunomide can potentially restore most of the neuronal damage in the hippocampal tissues of AlCl3-induced AD rats. Reference: Naunyn Schmiedebergs Arch Pharmacol. 2022 Nov 17. https://pubmed.ncbi.nlm.nih.gov/36385687/

	Solvent	mg/mL	mM
Solubility
	DMF	25.0	92.52
	DMF:PBS (pH 7.2) (1:1)	0.5	1.85
	DMSO	40.2	148.90
	Ethanol	37.0	136.93

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 270.21 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. Ozturk S, Mathur D, Zhou RW, Mulholland D, Parsons R. Leflunomide triggers synthetic lethality in PTEN-deficient prostate cancer. Prostate Cancer Prostatic Dis. 2020 Dec;23(4):718-723. doi: 10.1038/s41391-020-0251-1. Epub 2020 Jul 13. PMID: 32661432; PMCID: PMC7666085. 2. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA. The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry. 1996 Jan 30;35(4):1270-3. doi: 10.1021/bi952168g. PMID: 8573583. 3. Nafea M, Elharoun M, Abd-Alhaseeb MM, Helmy MW. Leflunomide abrogates neuroinflammatory changes in a rat model of Alzheimer's disease: the role of TNF-α/NF-κB/IL-1β axis inhibition. Naunyn Schmiedebergs Arch Pharmacol. 2022 Nov 17. doi: 10.1007/s00210-022-02322-3. Epub ahead of print. PMID: 36385687. 4. Aljohani AA, Alqarni YS, Alrashidi MN, Aljuhani MH, Shehata SA, El-Kherbetawy MK, Prabahar K, Alshaman R, Alattar A, Helaly AMN, Ateyya H, Ismail EA, Zaitone SA. The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFβ-Mediated p53/Smad2/3 Signaling. Toxics. 2022 May 23;10(5):274. doi: 10.3390/toxics10050274. PMID: 35622687; PMCID: PMC9144816.

In vitro protocol:

In vivo protocol:

1. Nafea M, Elharoun M, Abd-Alhaseeb MM, Helmy MW. Leflunomide abrogates neuroinflammatory changes in a rat model of Alzheimer's disease: the role of TNF-α/NF-κB/IL-1β axis inhibition. Naunyn Schmiedebergs Arch Pharmacol. 2022 Nov 17. doi: 10.1007/s00210-022-02322-3. Epub ahead of print. PMID: 36385687. 2. Aljohani AA, Alqarni YS, Alrashidi MN, Aljuhani MH, Shehata SA, El-Kherbetawy MK, Prabahar K, Alshaman R, Alattar A, Helaly AMN, Ateyya H, Ismail EA, Zaitone SA. The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFβ-Mediated p53/Smad2/3 Signaling. Toxics. 2022 May 23;10(5):274. doi: 10.3390/toxics10050274. PMID: 35622687; PMCID: PMC9144816.

1: Fragoso YD, Brooks JB. Leflunomide and teriflunomide: altering the metabolism of pyrimidines for the treatment of autoimmune diseases. Expert Rev Clin Pharmacol. 2015 May;8(3):315-20. doi: 10.1586/17512433.2015.1019343. Epub 2015 Feb 24. Review. PubMed PMID: 25712857. 2: Soukup T, Dosedel M, Nekvindova J, Toms J, Vlcek J, Pavek P. Genetic polymorphisms in metabolic pathways of leflunomide in the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2015 May-Jun;33(3):426-32. Epub 2015 Jan 29. Review. PubMed PMID: 25664505. 3: Smith KJ, Germain M. Leflunomide: an immune modulating drug that may have a role in controlling secondary infections with review of its mechanisms of action. J Drugs Dermatol. 2015 Mar;14(3):230-6. Review. PubMed PMID: 25738844. 4: Verkaik NJ, Hoek RA, van Bergeijk H, van Hal PT, Schipper ME, Pas SD, Beersma MF, Boucher CA, Jedema I, Falkenburg F, Hoogsteden HC, van den Blink B, Murk JL. Leflunomide as part of the treatment for multidrug-resistant cytomegalovirus disease after lung transplantation: case report and review of the literature. Transpl Infect Dis. 2013 Dec;15(6):E243-9. doi: 10.1111/tid.12156. Epub 2013 Oct 23. Review. PubMed PMID: 24298985. 5: Keen HI, Conaghan PG, Tett SE. Safety evaluation of leflunomide in rheumatoid arthritis. Expert Opin Drug Saf. 2013 Jul;12(4):581-8. doi: 10.1517/14740338.2013.798299. Epub 2013 May 14. Review. PubMed PMID: 23668332. 6: Pinto B, Dhir V, Krishnan S, Nada R. Leflunomide-induced DRESS syndrome with renal involvement and vasculitis. Clin Rheumatol. 2013 May;32(5):689-93. doi: 10.1007/s10067-012-2152-8. Epub 2012 Dec 28. Review. PubMed PMID: 23271613. 7: Sehgal VN, Verma P. Leflunomide: dermatologic perspective. J Dermatolog Treat. 2013 Apr;24(2):89-95. doi: 10.3109/09546634.2011.595383. Epub 2011 Jul 31. Review. PubMed PMID: 21801113. 8: Jung YH, Moon KC, Ha JW, Kim SJ, Ha IS, Cheong HI, Kang HG. Leflunomide therapy for BK virus allograft nephropathy after pediatric kidney transplantation. Pediatr Transplant. 2013 Mar;17(2):E50-4. doi: 10.1111/petr.12029. Epub 2012 Dec 4. Review. PubMed PMID: 23210794. 9: Wu GC, Xu XD, Huang Q, Wu H. Leflunomide: friend or foe for systemic lupus erythematosus? Rheumatol Int. 2013 Feb;33(2):273-6. doi: 10.1007/s00296-012-2508-z. Epub 2012 Sep 8. Review. PubMed PMID: 22961090. 10: Boyd AS. Leflunomide in dermatology. J Am Acad Dermatol. 2012 Apr;66(4):673-9. doi: 10.1016/j.jaad.2011.08.025. Epub 2011 Oct 1. Review. PubMed PMID: 21962758. 11: Navarro R, Daudén E, Gallo E, Santiago Sánchez-Mateos D, García-Diez A. Alopecia areata during treatment of psoriasis with adalimumab and leflunomide: a case and review of the literature. Skin Pharmacol Physiol. 2012;25(2):107-10. doi: 10.1159/000335264. Epub 2012 Jan 31. Review. PubMed PMID: 22301842. 12: Golicki D, Newada M, Lis J, Pol K, Hermanowski T, Tłustochowicz M. Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trials. Pol Arch Med Wewn. 2012;122(1-2):22-32. Epub 2012 Jan 11. Review. PubMed PMID: 22353705. 13: Sawada T. [Treatment of rheumatic diseases: current status and future prospective. Topics: II. Immunosuppressant/antirheumatic drugs; 5. Leflunomide and mizoribine]. Nihon Naika Gakkai Zasshi. 2011 Oct 10;100(10):2929-35. Review. Japanese. PubMed PMID: 22175133. 14: Inokuma S. Leflunomide-induced interstitial pneumonitis might be a representative of disease-modifying antirheumatic drug-induced lung injury. Expert Opin Drug Saf. 2011 Jul;10(4):603-11. doi: 10.1517/14740338.2011.560835. Epub 2011 Mar 17. Review. PubMed PMID: 21410426. 15: Kim SH, Yoo WH. Recurrent pneumothorax associated with pulmonary nodules after leflunomide therapy in rheumatoid arthritis: a case report and review of the literature. Rheumatol Int. 2011 Jul;31(7):919-22. doi: 10.1007/s00296-009-1240-9. Epub 2009 Oct 28. Review. PubMed PMID: 19862529. 16: Dai L, Wei XN, Zheng DH, Mo YQ, Pessler F, Zhang BY. Effective treatment of Kimura's disease with leflunomide in combination with glucocorticoids. Clin Rheumatol. 2011 Jun;30(6):859-65. doi: 10.1007/s10067-011-1689-2. Epub 2011 Feb 1. Review. PubMed PMID: 21286771. 17: Singer O, Gibofsky A. Methotrexate versus leflunomide in rheumatoid arthritis: what is new in 2011? Curr Opin Rheumatol. 2011 May;23(3):288-92. doi: 10.1097/BOR.0b013e328344f2e4. Review. PubMed PMID: 21378570. 18: Chon WJ, Josephson MA. Leflunomide in renal transplantation. Expert Rev Clin Immunol. 2011 May;7(3):273-81. doi: 10.1586/eci.11.20. Review. PubMed PMID: 21595593. 19: Behrens F, Koehm M, Burkhardt H. Update 2011: leflunomide in rheumatoid arthritis - strengths and weaknesses. Curr Opin Rheumatol. 2011 May;23(3):282-7. doi: 10.1097/BOR.0b013e328344fddb. Review. PubMed PMID: 21427581. 20: Antonio-Valdiviezo A, Peña-Santos G, Martínez-Torres J. [Peripheral neuropathy caused by leflunomide. A case reported with a brief review]. Rev Med Inst Mex Seguro Soc. 2010 Sep-Oct;48(5):567-70. Review. Spanish. PubMed PMID: 21205510.