Licofelone | ML-3000 | CAS#156897-06-2 | dual COX/LOX inhibitor

MedKoo Cat#: 326950 | Name: Licofelone

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Description:

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

Licofelone, also known as ML-3000, is a dual COX/LOX inhibitor potentially for the treatment of osteoarthritis. Licofelone is both an analgesic and an anti-inflammatory. Inhibition of 5-LOX may reduce the gastrointestinal toxicity associated with other non-steroidal anti-inflammatory drugs, which only inhibit COX (cyclooxygenase). Licofelone is the first drug to inhibit both.

Chemical Structure

Licofelone

CAS#156897-06-2

Theoretical Analysis

MedKoo Cat#: 326950

Name: Licofelone

CAS#: 156897-06-2

Chemical Formula: C23H22ClNO2

Exact Mass: 379.1339

Molecular Weight: 379.88

Elemental Analysis: C, 72.72; H, 5.84; Cl, 9.33; N, 3.69; O, 8.42

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
10mg	USD 600.00	2 Weeks

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Related CAS #

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Synonym

Licofelone; ML-3000; ML 3000; ML3000.

IUPAC/Chemical Name

(6-(4-Chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetic acid

InChi Key

UAWXGRJVZSAUSZ-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H22ClNO2/c1-23(2)13-19-22(15-6-4-3-5-7-15)21(16-8-10-17(24)11-9-16)18(12-20(26)27)25(19)14-23/h3-11H,12-14H2,1-2H3,(H,26,27)

SMILES Code

O=C(O)CC1=C(C2=CC=C(Cl)C=C2)C(C3=CC=CC=C3)=C4N1CC(C)(C)C4

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

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:

Licofelone (ML-3000) is a dual COX/5-lipoxygenase (5-LOX) inhibitor (IC50=0.21/0.18 μM, respectively) for the treatment of osteoarthritis.

In vitro activity:

The dual COX/5-LOX inhibitor licofelone triggers apoptosis in a dose- and time-dependent manner in HCA-7 colon cancer cells. Pre-treatment of HCA-7 cells with the pan-caspase inhibitor z-VAD-fmk significantly blocked licofelone-induced apoptosis, confirming that this process occurred primarily in a caspase-dependent pathway. Reference: Carcinogenesis. 2008 Feb;29(2):371-80. https://pubmed.ncbi.nlm.nih.gov/18033773/

In vivo activity:

Clonic seizures were induced in male NMRI mice by intravenous administration of pentylenetetrazol (PTZ). Acute administration of licofelone exerted anticonvulsant effects at 10 (p<0.01) and 20 mg/kg (p<0.001). A combined treatment with sub-effective doses of the selective NMDAR antagonist MK-801 (0.05 mg/kg, i.p.) and licofelone (5 mg/kg, i.p.) significantly (p<0.001) exerted an anticonvulsant effect on the PTZ-induced clonic seizures in mice. Reference: J Epilepsy Res. 2021 Jun 30;11(1):14-21. https://pubmed.ncbi.nlm.nih.gov/34395219/

	Solvent	mg/mL	mM
Solubility
	DMF	20.0	52.65
	DMSO	40.3	101.37
	DMSO:PBS (pH 7.2) (1:18	0.5	1.32
	Ethanol	21.5	56.50

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 379.88 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. Neumann S, Shirley SA, Kemp RA, Hook SM. Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone. Front Immunol. 2016 Dec 5;7:537. doi: 10.3389/fimmu.2016.00537. PMID: 27994586; PMCID: PMC5137024. 2. Tavolari S, Bonafè M, Marini M, Ferreri C, Bartolini G, Brighenti E, Manara S, Tomasi V, Laufer S, Guarnieri T. Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis. 2008 Feb;29(2):371-80. doi: 10.1093/carcin/bgm265. Epub 2007 Nov 21. PMID: 18033773. 3. Gholizadeh R, Abdolmaleki Z, Bahremand T, Ghasemi M, Gharghabi M, Dehpour AR. Involvement of N-Methyl-D-Aspartate Receptors in the Anticonvulsive Effects of Licofelone on Pentylenetetrazole-Induced Clonic Seizure in Mice. J Epilepsy Res. 2021 Jun 30;11(1):14-21. doi: 10.14581/jer.21003. PMID: 34395219; PMCID: PMC8357553. 4. Nikoui V, Mehrzadi S, Khan MI, Aman W, Ostadhadi S, Dehpour AR. Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats. Eur J Pharmacol. 2020 Nov 15;887:173569. doi: 10.1016/j.ejphar.2020.173569. Epub 2020 Sep 16. PMID: 32949599.

In vitro protocol:

In vivo protocol:

1. Gholizadeh R, Abdolmaleki Z, Bahremand T, Ghasemi M, Gharghabi M, Dehpour AR. Involvement of N-Methyl-D-Aspartate Receptors in the Anticonvulsive Effects of Licofelone on Pentylenetetrazole-Induced Clonic Seizure in Mice. J Epilepsy Res. 2021 Jun 30;11(1):14-21. doi: 10.14581/jer.21003. PMID: 34395219; PMCID: PMC8357553. 2. Nikoui V, Mehrzadi S, Khan MI, Aman W, Ostadhadi S, Dehpour AR. Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats. Eur J Pharmacol. 2020 Nov 15;887:173569. doi: 10.1016/j.ejphar.2020.173569. Epub 2020 Sep 16. PMID: 32949599.

1: Payandemehr B, Khoshneviszadeh M, Varastehmoradi B, Gholizadeh R, Bahremand T, Attar H, Bahremand A, Dehpour AR. A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice. Neurochem Res. 2015 Sep;40(9):1819-28. doi: 10.1007/s11064-015-1669-z. Epub 2015 Jul 28. PubMed PMID: 26216049. 2: Balansky R, Ganchev G, Iltcheva M, Nikolov M, Maestra SL, Micale RT, D'Agostini F, Steele VE, De Flora S. Modulation by licofelone and celecoxib of experimentally induced cancer and preneoplastic lesions in mice exposed to cigarette smoke. Curr Cancer Drug Targets. 2015;15(3):188-95. PubMed PMID: 25687474. 3: Kumar A, Sharma S, Prashar A, Deshmukh R. Effect of licofelone--a dual COX/5-LOX inhibitor in intracerebroventricular streptozotocin-induced behavioral and biochemical abnormalities in rats. J Mol Neurosci. 2015 Mar;55(3):749-59. doi: 10.1007/s12031-014-0414-4. Epub 2014 Sep 10. PubMed PMID: 25204299. 4: Zhang K, Zhao J, Su W, Lu R, Lv P. Immunomodulatory effectiveness of licofelone in preventing epidural fibrosis in post-laminectomy rat. Eur J Orthop Surg Traumatol. 2015 Jul;25 Suppl 1:S63-8. doi: 10.1007/s00590-014-1534-9. Epub 2014 Sep 9. PubMed PMID: 25200318. 5: Madka V, Mohammed A, Li Q, Zhang Y, Patlolla JM, Biddick L, Lightfoot S, Wu XR, Steele V, Kopelovich L, Rao CV. Chemoprevention of urothelial cell carcinoma growth and invasion by the dual COX-LOX inhibitor licofelone in UPII-SV40T transgenic mice. Cancer Prev Res (Phila). 2014 Jul;7(7):708-16. doi: 10.1158/1940-6207.CAPR-14-0087. Epub 2014 May 2. PubMed PMID: 24795386; PubMed Central PMCID: PMC4310686. 6: Kus G, Oztopcu-Vatan P, Uyar R, Kabadere S. Cytotoxic and apoptotic functions of licofelone on rat glioma cells. Acta Biol Hung. 2013 Dec;64(4):438-52. doi: 10.1556/ABiol.64.2013.4.4. PubMed PMID: 24275590. 7: Kabadere S, Kus G, Uyar R, Oztopcu-Vatan P. Licofelone abolishes survival of carcinogenic fibroblasts by inducing apoptosis. Drug Chem Toxicol. 2014 Jan;37(1):1-7. doi: 10.3109/01480545.2013.806525. Epub 2013 Jul 8. PubMed PMID: 23834160. 8: Dulin JN, Karoly ED, Wang Y, Strobel HW, Grill RJ. Licofelone modulates neuroinflammation and attenuates mechanical hypersensitivity in the chronic phase of spinal cord injury. J Neurosci. 2013 Jan 9;33(2):652-64. doi: 10.1523/JNEUROSCI.6128-11.2013. PubMed PMID: 23303944; PubMed Central PMCID: PMC3586230. 9: Kumar A, Vashist A, Kumar P, Kalonia H, Mishra J. Potential role of licofelone, minocycline and their combination against chronic fatigue stress induced behavioral, biochemical and mitochondrial alterations in mice. Pharmacol Rep. 2012;64(5):1105-15. PubMed PMID: 23238467. 10: Dulin JN, Moore ML, Grill RJ. The dual cyclooxygenase/5-lipoxygenase inhibitor licofelone attenuates p-glycoprotein-mediated drug resistance in the injured spinal cord. J Neurotrauma. 2013 Feb 1;30(3):211-26. doi: 10.1089/neu.2012.2587. Epub 2013 Jan 23. PubMed PMID: 22947335; PubMed Central PMCID: PMC3565554. 11: Wu YJ, Xue M, Chen H. Licofelone inhibits interleukin-18-induced pro-inflammatory cytokine release and cellular proliferation in human mesangial cells. Basic Clin Pharmacol Toxicol. 2012 Sep;111(3):166-72. doi: 10.1111/j.1742-7843.2012.00882.x. Epub 2012 Apr 11. PubMed PMID: 22433003. 12: Tavolari S, Munarini A, Storci G, Laufer S, Chieco P, Guarnieri T. The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cells. Cancer Lett. 2012 Aug 28;321(2):187-94. doi: 10.1016/j.canlet.2012.02.003. Epub 2012 Feb 14. PubMed PMID: 22343320. 13: Mohammed A, Janakiram NB, Li Q, Choi CI, Zhang Y, Steele VE, Rao CV. Chemoprevention of colon and small intestinal tumorigenesis in APC(Min/+) mice by licofelone, a novel dual 5-LOX/COX inhibitor: potential implications for human colon cancer prevention. Cancer Prev Res (Phila). 2011 Dec;4(12):2015-26. doi: 10.1158/1940-6207.CAPR-11-0233. Epub 2011 Sep 1. PubMed PMID: 21885812; PubMed Central PMCID: PMC3232346. 14: Liu W, Zhou J, Liu Y, Liu H, Bensdorf K, Guo C, Gust R. Licofelone-nitric oxide donors as anticancer agents. Arch Pharm (Weinheim). 2011 Aug;344(8):487-93. doi: 10.1002/ardp.201000397. Epub 2011 Jun 16. PubMed PMID: 21681808. 15: Sharma S, Lee J, Zhou J, Steele VE. Chemopreventive efficacy and mechanism of licofelone in a mouse lung tumor model via aspiration. Cancer Prev Res (Phila). 2011 Aug;4(8):1233-42. doi: 10.1158/1940-6207.CAPR-10-0117. Epub 2011 May 11. PubMed PMID: 21562034; PubMed Central PMCID: PMC3151334. 16: Kumar P, Kalonia H, Kumar A. Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats: protective effect of licofelone. Br J Pharmacol. 2011 Sep;164(2b):644-54. doi: 10.1111/j.1476-5381.2011.01418.x. PubMed PMID: 21486276; PubMed Central PMCID: PMC3188893. 17: Liu W, Zhou J, Bensdorf K, Zhang H, Liu H, Wang Y, Qian H, Zhang Y, Wellner A, Rubner G, Huang W, Guo C, Gust R. Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives. Eur J Med Chem. 2011 Mar;46(3):907-13. doi: 10.1016/j.ejmech.2011.01.002. Epub 2011 Jan 11. PubMed PMID: 21295381. 18: Kalonia H, Kumar P, Kumar A. Licofelone attenuates quinolinic acid induced Huntington like symptoms: possible behavioral, biochemical and cellular alterations. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):607-15. doi: 10.1016/j.pnpbp.2011.01.003. Epub 2011 Jan 13. PubMed PMID: 21237233. 19: Gupta A, Kumar A, Kulkarni SK. Licofelone attenuates MPTP-induced neuronal toxicity: behavioral, biochemical and cellular evidence. Inflammopharmacology. 2010 Oct;18(5):223-32. doi: 10.1007/s10787-010-0052-6. Epub 2010 Aug 11. PubMed PMID: 20697819. 20: Raynauld JP, Martel-Pelletier J, Bias P, Laufer S, Haraoui B, Choquette D, Beaulieu AD, Abram F, Dorais M, Vignon E, Pelletier JP; Canadian Licofelone Study Group. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis. 2009 Jun;68(6):938-47. doi: 10.1136/ard.2008.088732. Epub 2008 Jul 23. PubMed PMID: 18653484.