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

MedKoo CAT#: 205968

CAS#: 55837-20-2

Description: Halofuginone, also known as RU-19110, is a semisynthetic quinazolinone alkaloid anticoccidial derived from the plant Dichroa febrifuga, with antifibrotic and potential antineoplastic activities. Halofuginone specifically inhibits collagen type I gene expression and matrix metalloproteinase 2 (MMP-2) gene expression, which may result in the suppression of angiogenesis, tumor stromal cell development, and tumor cell growth. These effects appear to be due to halofuginone-mediated inhibition of the collagen type I and MMP-2 promoters.


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Halofuginone is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205968
Name: Halofuginone
CAS#: 55837-20-2
Chemical Formula: C16H17BrClN3O3
Exact Mass: 413.01418
Molecular Weight: 414.68
Elemental Analysis: C, 46.34; H, 4.13; Br, 19.27; Cl, 8.55; N, 10.13; O, 11.57


Synonym: RU 19110; RU19110; RU-19110; Halofuginone; Tempostatin.

IUPAC/Chemical Name: 7-bromo-6-chloro-3-(3-((2S,3R)-3-hydroxypiperidin-2-yl)-2-oxopropyl)quinazolin-4(3H)-one.

InChi Key: LVASCWIMLIKXLA-LSDHHAIUSA-N

InChi Code: InChI=1S/C16H17BrClN3O3/c17-11-6-13-10(5-12(11)18)16(24)21(8-20-13)7-9(22)4-14-15(23)2-1-3-19-14/h5-6,8,14-15,19,23H,1-4,7H2/t14-,15+/m0/s1

SMILES Code: O=C1N(CC(C[C@@H]2NCCC[C@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3


Technical Data

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).

Harmonized System Code:
293490


Additional Information

Halofuginone is a coccidiostat used in veterinary medicine. It is a synthetic halogenated derivative of febrifugine, a natural quinazolinone alkaloid which can be found in the Chinese herb Dichroa febrifuga (Chang Shan).  Collgard Biopharmaceuticals is developing halofuginone for the treatment of scleroderma and it has received orphan drug designation from the U.S. Food and Drug Administration. Halofuginone inhibits the development of T helper 17 cells, immune cells that play an important role in autoimmune disease, but it does not affect other kinds of T cells which involved in normal immune function.Halofuginone therefore has potential for the treatment of autoimmune disorders. Halofuginone is also an inhibitor of collagen type I gene expression and as a consequence it may inhibit tumor cell growth. Halofuginone exerts its effects by acting as a high affinity inhibitor of the enzyme Glutamyl-Prolyl tRNA synthetase. Inhibition of prolyl tRNA charging leads to the accumulation of uncharged prolyl tRNAs, which serve as a signal to initiate the amino acid starvation response, which in turn exerts anti-inflammatory and anti-fibrotic effects.  (source: http://en.wikipedia.org/wiki/Halofuginone)
 
 
 


References

1: Pines M, Spector I. Halofuginone - The Multifaceted Molecule. Molecules. 2015 Jan 5;20(1):573-594. Review. PubMed PMID: 25569515.

2: Pines M. Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract. World J Gastroenterol. 2014 Oct 28;20(40):14778-86. doi: 10.3748/wjg.v20.i40.14778. PubMed PMID: 25356039; PubMed Central PMCID: PMC4209542.

3: Guo LW, Wang B, Goel SA, Little C, Takayama T, Shi XD, Roenneburg D, DiRenzo D, Kent KC. Halofuginone stimulates adaptive remodeling and preserves re-endothelialization in balloon-injured rat carotid arteries. Circ Cardiovasc Interv. 2014 Aug;7(4):594-601. doi: 10.1161/CIRCINTERVENTIONS.113.001181. Epub 2014 Jul 29. PubMed PMID: 25074254; PubMed Central PMCID: PMC4140988.

4: Park MK, Park JS, Park EM, Lim MA, Kim SM, Lee DG, Baek SY, Yang EJ, Woo JW, Lee J, Kwok SK, Kim HY, Cho ML, Park SH. Halofuginone ameliorates autoimmune arthritis in mice by regulating the balance between Th17 and Treg cells and inhibiting osteoclastogenesis. Arthritis Rheumatol. 2014 May;66(5):1195-207. doi: 10.1002/art.38313. PubMed PMID: 24782183.

5: Bodanovsky A, Guttman N, Barzilai-Tutsch H, Genin O, Levy O, Pines M, Halevy O. Halofuginone improves muscle-cell survival in muscular dystrophies. Biochim Biophys Acta. 2014 Jul;1843(7):1339-47. doi: 10.1016/j.bbamcr.2014.03.025. Epub 2014 Apr 2. PubMed PMID: 24703880.

6: McLaughlin NP, Evans P, Pines M. The chemistry and biology of febrifugine and halofuginone. Bioorg Med Chem. 2014 Apr 1;22(7):1993-2004. doi: 10.1016/j.bmc.2014.02.040. Epub 2014 Mar 1. Review. PubMed PMID: 24650700.

7: Petermann J, Paraud C, Pors I, Chartier C. Efficacy of halofuginone lactate against experimental cryptosporidiosis in goat neonates. Vet Parasitol. 2014 May 28;202(3-4):326-9. doi: 10.1016/j.vetpar.2014.02.027. Epub 2014 Feb 22. PubMed PMID: 24636788.

8: Kapoor S. Reduction of burn scar formation by halofuginone-eluting silicone gel sheets: a controlled study on nude mice. Ann Plast Surg. 2014 Apr;72(4):489. doi: 10.1097/SAP.0b013e318281ad59. PubMed PMID: 24618743.

9: Carlson TJ, Pellerin A, Djuretic IM, Trivigno C, Koralov SB, Rao A, Sundrud MS. Halofuginone-induced amino acid starvation regulates Stat3-dependent Th17 effector function and reduces established autoimmune inflammation. J Immunol. 2014 Mar 1;192(5):2167-76. doi: 10.4049/jimmunol.1302316. Epub 2014 Jan 31. PubMed PMID: 24489094; PubMed Central PMCID: PMC3936195.

10: Jin C, Jia Y, Jin C, Dong H, Cheng P, Zhou J, Wang Y, Zheng B, Liu F. Therapeutic effect of Halofuginone on ITP mice by regulating the differentiation of Th cell subsets. Int Immunopharmacol. 2014 Feb;18(2):213-6. doi: 10.1016/j.intimp.2013.12.013. Epub 2013 Dec 22. PubMed PMID: 24368123.

11: Liang J, Zhang B, Shen RW, Liu JB, Gao MH, Li Y, Li YY, Zhang W. Preventive effect of halofuginone on concanavalin A-induced liver fibrosis. PLoS One. 2013 Dec 16;8(12):e82232. doi: 10.1371/journal.pone.0082232. eCollection 2013. PubMed PMID: 24358159; PubMed Central PMCID: PMC3864948.

12: Jin ML, Park SY, Kim YH, Park G, Lee SJ. Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9. Int J Oncol. 2014 Jan;44(1):309-18. doi: 10.3892/ijo.2013.2157. Epub 2013 Oct 31. PubMed PMID: 24173318.

13: Son J, Lee EH, Park M, Kim JH, Kim J, Kim S, Jeon YH, Hwang KY. Conformational changes in human prolyl-tRNA synthetase upon binding of the substrates proline and ATP and the inhibitor halofuginone. Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2136-45. doi: 10.1107/S0907444913020556. Epub 2013 Sep 20. PubMed PMID: 24100331.

14: Zeplin PH. Halofuginone down-regulates Smad3 expression and inhibits the TGFbeta-induced expression of fibrotic markers in human corneal fibroblasts. Ann Plast Surg. 2014 Apr;72(4):489. doi: 10.1097/SAP.0b013e31828a49e3. PubMed PMID: 23845969.

15: Almawly J, Prattley D, French NP, Lopez-Villalobos N, Hedgespeth B, Grinberg A. Utility of halofuginone lactate for the prevention of natural cryptosporidiosis of calves, in the presence of co-infection with rotavirus and Salmonella Typhimurium. Vet Parasitol. 2013 Oct 18;197(1-2):59-67. doi: 10.1016/j.vetpar.2013.04.029. Epub 2013 Apr 24. PubMed PMID: 23707392.

16: Chu TL, Guan Q, Nguan CY, Du C. Halofuginone suppresses T cell proliferation by blocking proline uptake and inducing cell apoptosis. Int Immunopharmacol. 2013 Aug;16(4):414-23. doi: 10.1016/j.intimp.2013.04.031. Epub 2013 May 16. PubMed PMID: 23685128.

17: Keidel J, Daugschies A. Integration of halofuginone lactate treatment and disinfection with p-chloro-m-cresol to control natural cryptosporidiosis in calves. Vet Parasitol. 2013 Sep 23;196(3-4):321-6. doi: 10.1016/j.vetpar.2013.03.003. Epub 2013 Mar 14. PubMed PMID: 23561324.

18: Yavas G, Calik M, Calik G, Yavas C, Ata O, Esme H. The effect of Halofuginone in the amelioration of radiation induced-lung fibrosis. Med Hypotheses. 2013 Apr;80(4):357-9. doi: 10.1016/j.mehy.2013.01.001. Epub 2013 Jan 23. PubMed PMID: 23352286.

19: Halevy O, Genin O, Barzilai-Tutsch H, Pima Y, Levi O, Moshe I, Pines M. Inhibition of muscle fibrosis and improvement of muscle histopathology in dysferlin knock-out mice treated with halofuginone. Histol Histopathol. 2013 Feb;28(2):211-26. PubMed PMID: 23275304.

20: Juárez P, Mohammad KS, Yin JJ, Fournier PG, McKenna RC, Davis HW, Peng XH, Niewolna M, Javelaud D, Chirgwin JM, Mauviel A, Guise TA. Halofuginone inhibits the establishment and progression of melanoma bone metastases. Cancer Res. 2012 Dec 1;72(23):6247-56. doi: 10.1158/0008-5472.CAN-12-1444. Epub 2012 Sep 20. PubMed PMID: 23002206.