Leflunomide (HWA486)

Catalog No.S1247 Synonyms: RS-34821, SU101, Arava

For research use only.

Leflunomide (HWA486, RS-34821, SU101, Arava) is a pyrimidine synthesis and protein tyrosine kinase inhibitor belonging to the DMARD, used as an immunosuppressant agent. The active metabolite of Leflunomide is A77 1726, which inhibits dihydroorotate dehydrogenase (DHODH). Leflunomide is also an agonist of the AhR.

Leflunomide (HWA486) Chemical Structure

CAS No. 75706-12-6

Selleck's Leflunomide (HWA486) has been cited by 11 Publications

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Biological Activity

Description Leflunomide (HWA486, RS-34821, SU101, Arava) is a pyrimidine synthesis and protein tyrosine kinase inhibitor belonging to the DMARD, used as an immunosuppressant agent. The active metabolite of Leflunomide is A77 1726, which inhibits dihydroorotate dehydrogenase (DHODH). Leflunomide is also an agonist of the AhR.
Targets
Dihydroorotate dehydrogenase [1]
In vitro

Leflunomide is actually a prodrug that is processed in vivo to the active metabolite A771726,which has been shown to inhibit proliferation of mononuclear and T-cells. Leflunomide is an inhibitor of several protein tyrosine kinases, with IC50 values between 30 mM and 100 mM in vitro cellular and enzymatic assays. [1] Leflunomide is capable of inhibiting anti-CD3- and interleukin-2 (IL-2)-stimulated T cell proliferation. Leflunomide is able to inhibit p59fyn and p56lck activity in in vitro tyrosine kinase assays. Leflunomide also inhibits Ca2+ mobilization in Jurkat cells stimulated by anti-CD3 antibody but not in those stimulated by ionomycin. Leflunomide also inhibits distal events of anti-CD3 monoclonal antibody stimulation, namely, IL-2 production and IL-2 receptor expression on human T lymphocytes. Leflunomide also inhibits tyrosine phosphorylation in CTLL-4 cells stimulated by IL-2. [2] Leflunomide is an immunomodulatory drug that may exert its effects by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which plays a key role in the de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP). Leflunomide prevents the expansion of activated and autoimmune lymphocytes by interfering with the cell cycle progression due to inadequate production of rUMP and utilizing mechanisms involving p53. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
B-cells M2T3UWZ2dmO2aX;uJIF{e2G7 M3rIXWlvKH[rdILvJIlvcGmkaYTpc44hd2ZiQXKg[o9zdWG2aX;uJIZzd21idILpcol1em:yaHXufYwudGmyb4DvcJl{[WOlaHHybYRmKCiWTmCtUHBUMSCELXPlcIx{NCCLQ{WwQVUvOc7:TR?= MlvBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTF|OESyOFMoRjFzM{i0NlQ{RC:jPh?=
A673 MWXxTHRUKGG|c3H5 NVvTTmF3eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFG2O|Mh[2WubIO= NHLIe5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-MC NXzyR5d1eUiWUzDhd5NigQ>? NVfpUoJreUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> NX61SIgzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC NHH1NZByUFSVIHHzd4F6 NIC1VmVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLV3DJINmdGy| NUDTdXhRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 29423085
Western blot DH0DH ; ATF4 / CHOP ; CDK2 / Cyclin A2 23977077 29427785 29348830
In vivo Leflunomide is able to prevent and reverse allograft and xenograft rejection in rodents, dogs, and monkeys. [2]

Protocol (from reference)

Solubility (25°C)

In vitro

DMSO 54 mg/mL
(199.84 mM)
Water Insoluble
Ethanol ''54 mg/mL

Chemical Information

Molecular Weight 270.21
Formula

C12H9F3N2O2

CAS No. 75706-12-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(C=NO1)C(=O)NC2=CC=C(C=C2)C(F)(F)F

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04212416 Recruiting Drug: Leflunomide Chronic Graft Versus Host Disease|Steroid Refractory Graft Versus Host Disease City of Hope Medical Center|National Cancer Institute (NCI) May 12 2020 Phase 1
NCT04361214 Recruiting Drug: Leflunomide COVID-19 University of Chicago May 5 2020 Phase 1
NCT03715699 Unknown status Drug: Prednisone|Drug: Prednisone and Leflunomide Autoimmune Disease Peking Union Medical College Hospital July 1 2018 Not Applicable
NCT03599986 Completed -- Active Rheumatoid Arthritis Eva Pharma|DataClin June 16 2017 --
NCT01500551 Recruiting Drug: Tofacitinib Juvenile Idiopathic Arthritis Pfizer March 18 2013 Phase 3

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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