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Leflunomide (HWA486)

Name: Leflunomide (HWA486)
Brand: Selleck Chemicals
SKU: S1247
Rating: 5 (11 reviews)

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.

CAS No. 75706-12-6

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

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Dehydrogenase Signaling Pathway Map

Biological Activity

Description

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=>

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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)

References

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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
Storage	2 years	-80°C	in solvent
Smiles	CC1=C(C=NO1)C(=O)NC2=CC=C(C=C2)C(F)(F)F

Download Leflunomide (HWA486) SDF

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

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

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

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)

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