Archive for May 24, 2012

HepatoChem Spring 2012 Newsletter

Collaboration With Prof. Michael Pollastri on Lead Diversification

HepatoChem Inc. and Prof. Michael Pollastri at Northeastern University initiated a collaboration on lead diversification of bioactive small molecules. The objective of this partnership is to discover new therapeutics using both the HepatoChem biomimetic technology and Pollastri’s approach, which consists of repurposing optimized human compound classes for neglected tropical diseases.

An example of Prof Pollastri’s approach is a parasitic target like trypanosomal phosphodiesterases has ~30% homology to human PDE4 and 5. That considered it becomes advantageous to use known human PDE4/5 inhibitors as a starting point to develop a new parasitic drug.

HepatoChem will bring its expertise in biomimetic technology to allow fast synthesis of new metabolite-like analogues. Indeed, the diversity expansion inherent in transformations that mimic the metabolism of small molecules and natural products provides a new direction into new chemical space. This new application is the result of the expansion of the spectrum of chemical reactions offered by HepatoChem to include halogenation and amination, in addition to oxidation.

This collaboration is part of the HepatoChem effort to develop and offer innovative tools for drug discovery. For more information about Prof Pollastri http://www.northeastern.edu/pollastri/

HepatoChem is a Recipient of the ‘Mass Life Science Center Life Science Center’s Accelerator Program

Mass Life Science Center Life Sciences Accelerator Program – Announces the 5 FY2012 Recipients on April 24, 2012

We are delighted to learn on April 24th that HepatoChem was one of five early stage companies to be awarded the Massachusetts Life Science Center Accelerator Program Loan for FY2012. “The $330,000.00 loan has arrived at the right time. Each month, small to big pharmaceutical organizations are turning to us to help them produce and characterize their drug candidate metabolites faster and in larger quantities than they could trying more traditional methods. To learn more …
http://www.marketwatch.com/story/hepatochem-is-one-of-five-early-stage-life-sciences-companies-awarded-the-massachusetts-life-sciences-center-accelerator-program-loan-for-fy-2012-2012-04-30

Cationic Iron(III) Porphyrin-Catalyzed [4 + 2] Cycloaddition of Unactivated Aldehydes with Simple Dienes

Usually iron porphyrin complexes are studies as models of heme proteins and as biomimetic oxidation catalysts. Interestingly, simple iron porphyrins can also catalyze other important transformations of organic compounds. The team of Kyohei Fujiwara, Takuya Kurahashi, and Seijiro Matsubara at Kyoto University have reported that the readily available cationic tetraphenyl iron(III) porphyrin (FeTPP) is an efficient catalyst for the highly chemoselective hetero-Diels−Alder reaction of aldehydes with conjugated dienes.

This reaction is one of the most powerful synthetic methods for the construction of heterocyclic compounds containing the pyran structural motif and has been widely applied in the preparation of drugs and natural products. Significantly, the process did not require activated reaction partners. A crystal structure of the catalyst shows that aryl aldehydes are activated by the catalyst via coordination of the carbonyl oxygen to the iron(III) center. High functional group tolerance was observed and a large variety of cycloadduct products were obtained in good to excellent yield. For example, phenyl-acetaldehyde underwent cycloaddition to afford a pyran in 72% yield. Thus, the catalyst is apparently able to suppress the high tendancy of this substrate to enolize. Cyclopropane carboxaldehyde, which is sensitive to rearrangement, also fomed a pyran in good yield. Significantly, the catalyst was shown to tolerate the presence of water.

Kyohei Fujiwara, Takuya Kurahashi, and Seijiro Matsubara, J. Am. Chem. Soc. 2012, 134, 5512−5515

Proximal Ligand Electron Donation and Reactivity of the Cytochrome P450 Ferric−Peroxo Anion

Cytochrome P450 enzymes, also called CYPs, are heme proteins with unusual cycteine-derived axial thiolate ligands that catalyze a wide variety of biological oxidations. In humans so-caled phase I metabolism of drugs results from P450-mediated oxidations. However, thousands of P450 proteins have been identified throughout biology that oxygenate all sorts of organic compounds compounds, including fatty acids, steroids, and xenobiotics. For a vast majority of bacterial P450s the subsrates and functions remain unknown. Some, such as EryF, are known to be involved in the biosynthesis of antibiotics, while others, such as P450cam (CYP101) are involved terpene catabolism.

CYP125 from Mycobacterium tuberculosis catalyzes the conversion of the terminal side-chain methyl group of cholesterol to various oxygenated states, alcohol, aldehyde and carboxylic acid. Paul R. Ortiz de Montellano and his group at UC San Francisco have recently reported that that CYP125 also the deformylation of the sterol side chain. The aldehyde intermediate is shown to be the precursor of both the conventional acid metabolite and the five deformylation products. These deformylation products are thought to arise from a reaction of the aldehyde intermedaite with a deprotonated ferric-peroxo intermediate, (heme)Fe(III)-O-O-. Replacement of the coordinating cysteine sulfur with selenium led to a product distribution with less of the deformylation products and more terminal side chain carboxylic acid. The results are interpreted to derive from an increase in the pKa of the ferric− peroxo anion in the selenium derivative as compared to the natural cysteine sulfur coordination.

In the early stages of MTb infection, the bacterium invades the aveolar macrophage (white) cells of the lung. These are the very cells usually responsible for bacterial killing and general house keeping. Remarkably, however, MTb is able to disable the bacteriocidal activities of the aveolar macrophage and propagate within the host cell. Once ensconced within the host, MTb uses cholesterol derived from the host as food. Furthermore, the steroid nucleus is then tailored by various oxidizing proteins in the bacterium to extend its control over the host cell. Studies such as these that reveal the pathways used by MTb to manipulate cholesterol may reveal drugable targets to help control this terrible disease.

Santhosh Sivaramakrishnan, Hugues Ouellet, Hirotoshi Matsumura,Shenheng Guan, Pierre Moënne-Loccoz, Alma L. Burlingame,and Paul R. Ortiz de Montellano, J. Am. Chem. Soc. 2012, ASAP, published on-line March 23, 2012. DOI: 10.1021/ja211499q

HepatoChem Presents at Early Stage Technology Event

UMASS MATTC Center’s VII Annual Event Features HepatoChem
Marc Bazin, CEO President, and Co-Founder, HepatoChem presented at the UMASS MATTC Center’s VII Annual ‘The Early-Stage Life Sciences Technology Conference’ on Thursday, April 12, 2012 at the Merck Research Laboratories to over 200 angel investors, venture capitalists and corporate investors. For more information…..
http://www.mattcenter.org/lsconf2012/home.html

Nucleus Article About HepatoChem Reachs the Greater Boston ACS Community

In a recent article of the Nucleus, the newspaper of the New-England ACS section, HepatoChem’s president was interviewed. You can find this article on the NE-ACS website. For more details – http://www.nesacs.org/
For more information contact:

Shelley Amster, Director Business Development, HepatoChem
Phone: (978) 371-5901
Mobile: (978) 239-1468
Email: shelley.amster@hepatochem.com

NEDMDG Summer Symposium

Northeastern Section of the Drug Metabolism Group (NEDMDG) of the American Chemical Society NEDMDG Summer Symposium, NEDMDG Summer Symposium will be held on Wednesday, June 13, 2012, at the Hoagland-Pincus Conference Center in Shrewsbury, MA. HepatoChem will be exhibiting at this all day event. See you there!

http://www.nedmdg.org/events.html

HepatoChem Awarded Massachusetts Life Sciences Center Accelerator Program Loan

BEVERLY, Mass., Apr 30, 2012 (BUSINESS WIRE) — HepatoChem, Inc. has announced that it has been awarded a $330,000 loan from the Massachusetts Life Sciences Center, a quasi-public agency tasked with implementing the State’s $1 billion Life Sciences Initiative (MLSC). HepatoChem is an early stage life science company with a game changing, proprietary chemistry platform that enables fast and cost effective metabolite production from bioactive small molecules. The HepatoChem technology enables assessment of critical metabolite and toxicity issues relatively early in the R&D continuum, reducing the risk of failure in clinical development of drug candidates.

HepatoChem is one of only five companies, out of a total of over eighty applicants, to receive a share of the $3.4 million in loans from the MLSC’s 2012 Accelerator Program. HepatoChem is a member company in the Biotech InnoVenture Center (BIVC) in Beverly, MA. BIVC is a non-profit accelerator for life sciences companies with fully equipped laboratory facilities hosted by New England PharmAssociates and operated by North Shore InnoVentures (NSIV) at the Cummings Center in Beverly.

“Our role at NSIV is to bring shared physical resources, sponsor services, experienced entrepreneurial mentors and investor advisors together with promising young companies to help them conserve capital, build strong teams and achieve development and funding milestones,” explains Martha Farmer, President and CEO of NSIV. “Not only is HepatoChem the first of our member companies to obtain support from MLSC but MLSC also helped NSIV start up our shared incubator laboratory facilities with an award in 2010.” As HepatoChem President, Marc Bazin observed, “The incubator is a key component for our success and this award validates how useful such an organization can be for economic growth in the North Shore.”

“Marc and his team, as well as his board, are quick to recognize opportunity, listen to advice and move accordingly. Mentoring Marc and his company is a real joy,” remarked Richard Gabriel, the NSIV Mentor to HepatoChem. Mr. Gabriel continued, “This technology will revolutionize drug development; anyone that isn’t using HepatoChem’s technology is going to be stuck in the old drug development paradigm. The FDA has changed the rules with its recent opinions on metabolites, placing HepatoChem in the forefront in this business.”

“I have known Marc since he conceived the unique approach for HepatoChem when we were both working at Pfizer. Marc has developed the idea of synthetic metabolites to the point where it can be a powerful force in accelerating drug discovery. He has carefully engaged supportive and committed individuals to advise HepatoChem, so when he asked me to join his Board, I was honored and thrilled to help him,” pointed out Nick Terrett, currently CSO of Ensemble Therapeutics, a Cambridge, MA biotech company.

About HepatoChem

HepatoChem, Inc. of Beverly, Massachusetts was founded in 2008, is a revenue generating early stage life science company that has licensed and built on a technology from Princeton University. Its approach is to alleviate the difficult if not impossible process to synthesize proprietary small molecules for the drug industry based on unique chemical reactions allowed by porphyrins and other catalysts. For more information, visit https://www.hepatochem.com

About North Shore InnoVentures

North Shore InnoVentures, a non-profit 501c3 business accelerator headquartered at the Cummings Center in Beverly, MA (NSIV), is dedicated to assisting early stage biotech and cleantech companies in our dedicated incubators grow and commercialize their businesses to assist in the economic growth of the North Shore region. NSIV’s leadership team, board of directors, advisory board members, and mentors bring a wealth of knowledge in diverse areas including entrepreneurship, experience in the biomedical and cleantech industries as well as economic and business development, venture capital and seed funding, marketing, legal, operational and educational services. For more information visit www.nsiv.org .