Antiproliferative compositions comprising curcumin analogs and methods of producing and using same
Patent Number: US9359196
Executive Summary:
General Description:
This invention is a novel curcumin analog (CLEFMA) encapsulated within a liposomal structure for the treatment of several cancers, including lung cancer. Curcumin is a naturally occurring anti-oxidant and anti-inflammatory agent derived from the rhizome of Curcuma longa, a commonly used Indian spice tumeric. It has been shown to be useful for the prevention and treatment of several disorders, including cancer and inflammatory diseases. Analogs and innovative formulations are being developed to improve curcumin bioavailability and effectiveness
Scientific Progress:
Validation of the anti-tumor activity of CLEFMA liposomes in nude rats and mice bearing xenograft lung adenocarcinoma H441 tumors. The biodistribution of CLEFMA liposomes was evaluated, and their uptake in tumor was improved compared to the parent compound. No apparent toxicity was found in rats after multiple administrations
Future Directions:
Strengths:
Weaknesses:
Numerous curcumin analogs and formulations are being studied for their anti-cancer properties. Some are evaluated in clinical trials. Moreover, curcumin capsules are already available on the market (Curamin ®, CuraMed ® for example) to improve various health conditions
Patent Status:
Legal Status: Active
Publication PMID: 25204337, 24102070, 21181232, 21315563, 20638855
Publications:
Yadav VR, Hussain A, Sahoo K, Awasthi V. Remediation of hemorrhagic shock-induced intestinal barrier dysfunction by treatment with diphenyldihaloketones EF24 and CLEFMA. J Pharmacol Exp Ther. 2014 Nov;351(2):413-22. doi: 10.1124/jpet.114.217331. Epub 2014 Sep 9.
Yadav VR, Sahoo K, Awasthi V. Preclinical evaluation of 4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid, in a mouse model of lung cancer xenograft. Br J Pharmacol. 2013 Dec;170(7):1436-48. doi: 10.1111/bph.12406.
Sahoo K, Dozmorov MG, Anant S, Awasthi V. The curcuminoid CLEFMA selectively induces cell death in H441 lung adenocarcinoma cells via oxidative stress. Invest New Drugs. 2012 Apr;30(2):558-67. doi: 10.1007/s10637-010-9610-4. Epub 2010 Dec 22.
Agashe H, Sahoo K, Lagisetty P, Awasthi V. Cyclodextrin-mediated entrapment of curcuminoid 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] or CLEFMA in liposomes for treatment of xenograft lung tumor in rats. Colloids Surf B Biointerfaces. 2011 Jun 1;84(2):329-37. doi: 10.1016/j.colsurfb.2011.01.023. Epub 2011 Jan 25.
Lagisetty P, Vilekar P, Sahoo K, Anant S, Awasthi V. CLEFMA-an anti-proliferative curcuminoid from structure-activity relationship studies on 3,5-bis(benzylidene)-4-piperidones. Bioorg Med Chem. 2010 Aug 15;18(16):6109-20. doi: 10.1016/j.bmc.2010.06.055. Epub 2010 Jun 22.
Inventor Bio: Vibhudutta Awasthi
http://pharmacy.ouhsc.edu/people/view.asp?User=vawasthi
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: US Grant
- Patent Link: https://patents.google.com/patent/US9359196/
- Research Institute: University of Oklahoma
- Disease Focus: Cancers, including lung cancer
- Basis of Invention: Curcumin analogs, comprising 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (CLEFMA), that possess antiproliferative activity
- How it works: The exact mechanism of action of curcumin is unknown, but CLEFMA appears to suppress cancer cell proliferation by inducing oxidative stress and autophagy. The liposomal encapsulation of CLEFMA improves its solubility and bioavailability
- Lead Challenge Inventor: Vibhudutta Awasthi
- Inventors: Vibhudutta Awasthi, Pallavi Lagisetty, Hrushikesh Agashe
- Development Stage: Preclinical (PK/PD, toxicity and efficacy data)
- Novelty: Novel curcumin analog encapsulated within a liposomal structure to improve its bioavailability and effectiveness
- Clinical Applications: Cancers (including lung cancer) and inflammatory diseases (including Alzheimer’s disease), hemorrhagic shock and ischemia/reperfusion injury
General Description:
This invention is a novel curcumin analog (CLEFMA) encapsulated within a liposomal structure for the treatment of several cancers, including lung cancer. Curcumin is a naturally occurring anti-oxidant and anti-inflammatory agent derived from the rhizome of Curcuma longa, a commonly used Indian spice tumeric. It has been shown to be useful for the prevention and treatment of several disorders, including cancer and inflammatory diseases. Analogs and innovative formulations are being developed to improve curcumin bioavailability and effectiveness
Scientific Progress:
Validation of the anti-tumor activity of CLEFMA liposomes in nude rats and mice bearing xenograft lung adenocarcinoma H441 tumors. The biodistribution of CLEFMA liposomes was evaluated, and their uptake in tumor was improved compared to the parent compound. No apparent toxicity was found in rats after multiple administrations
Future Directions:
- Validation in genetic mouse models for lung cancer
- Clinical proof-of-concept
Strengths:
- Increased bioavailability and efficacy due to liposomal encapsulation
- PK/PD and toxicity data available
Weaknesses:
Numerous curcumin analogs and formulations are being studied for their anti-cancer properties. Some are evaluated in clinical trials. Moreover, curcumin capsules are already available on the market (Curamin ®, CuraMed ® for example) to improve various health conditions
Patent Status:
Legal Status: Active
- Priority date: 2009.09.10
- Filing date: 2011.10.24
- Publication date: 2016.06.07
- Grant date: 2016.06.07
Publication PMID: 25204337, 24102070, 21181232, 21315563, 20638855
Publications:
Yadav VR, Hussain A, Sahoo K, Awasthi V. Remediation of hemorrhagic shock-induced intestinal barrier dysfunction by treatment with diphenyldihaloketones EF24 and CLEFMA. J Pharmacol Exp Ther. 2014 Nov;351(2):413-22. doi: 10.1124/jpet.114.217331. Epub 2014 Sep 9.
Yadav VR, Sahoo K, Awasthi V. Preclinical evaluation of 4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid, in a mouse model of lung cancer xenograft. Br J Pharmacol. 2013 Dec;170(7):1436-48. doi: 10.1111/bph.12406.
Sahoo K, Dozmorov MG, Anant S, Awasthi V. The curcuminoid CLEFMA selectively induces cell death in H441 lung adenocarcinoma cells via oxidative stress. Invest New Drugs. 2012 Apr;30(2):558-67. doi: 10.1007/s10637-010-9610-4. Epub 2010 Dec 22.
Agashe H, Sahoo K, Lagisetty P, Awasthi V. Cyclodextrin-mediated entrapment of curcuminoid 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] or CLEFMA in liposomes for treatment of xenograft lung tumor in rats. Colloids Surf B Biointerfaces. 2011 Jun 1;84(2):329-37. doi: 10.1016/j.colsurfb.2011.01.023. Epub 2011 Jan 25.
Lagisetty P, Vilekar P, Sahoo K, Anant S, Awasthi V. CLEFMA-an anti-proliferative curcuminoid from structure-activity relationship studies on 3,5-bis(benzylidene)-4-piperidones. Bioorg Med Chem. 2010 Aug 15;18(16):6109-20. doi: 10.1016/j.bmc.2010.06.055. Epub 2010 Jun 22.
Inventor Bio: Vibhudutta Awasthi
http://pharmacy.ouhsc.edu/people/view.asp?User=vawasthi