Yes, I know that pic is old. And that Brian Sabean appears to be holding a Motorola flip phone in his hand. I use it, however, because (a) it?s awesome; and (b) it underscores just how long that dude has been in charge of the Giants.
And it will be a little longer now, because the Giants have just announced that the contracts of Sabean and manager Bruce Bochy have been extended through 2013 with club options for 2014.
Sabean has had his job since 1996, meaning that by the time this deal is up, assuming the option is picked up, he will have been at the helm for 18 years. ?Bochy has been the Giants? manager since 2007. ?Before that he had 12 years in the Padres dugout. ?Say what you want about any one of their deals or moves, but these two are consistency and stability personified, and that?s worth something.
And now, with extra job security at their disposal, each of them can proceed to do exactly what they want this offseason: sign Jeromy Burnitz or someone a lot like him to a three-year deal.
TUESDAY, Nov. 22 (HealthDay News) -- Some patients with inflammatory bowel disease may be at increased risk for skin cancer due to their use of immunosuppressant drugs to treat the intestinal disorder, according to the results of two new studies.
The studies, published in the November issue of the journal Gastroenterology, noted that immunosuppressants are commonly used to treat patients with inflammatory bowel disease, or IBD. Currently, there are no specific recommendations for skin cancer screening in IBD patients.
In one study, French researchers led by Dr. Laurent Peyrin-Biroulet, of University Hospital of Nancy, found that both past and present use of a widely used class of immunosuppressants called thiopurines significantly increased the risk of non-melanoma skin cancer in inflammatory bowel disease patients.
"The increased risk of skin cancer that we found in our study was observed in all patients, even before the age of 50 years. As expected, this risk increased with age. All patients with inflammatory bowel disease currently receiving or having previously received thiopurines should protect their skin from UV radiation and receive regular dermatologic screening, regardless of their age," Peyrin-Biroulet said in a news release from the American Gastroenterological Association.
Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma, which are the most common cancers diagnosed in North America.
In the second study, Canadian researchers found that certain people with inflammatory bowel disease, such as men with a form of the disorder known as Crohn's disease, may already be at increased risk for basal cell carcinoma, and the use of thiopurines increases this risk.
"All individuals should be protecting themselves against skin cancer," lead author Dr. Harminder Singh, of the University of Manitoba, said in the news release. "But, it is especially important that physicians stress the need to be extra vigilant about skin care with their inflammatory bowel disease patients, especially among those exposed to immunosuppressants such as thiopurines."
However, Singh and his colleagues added that there was only a small absolute increased risk of non-melanoma skin cancer seen in the study, which may not warrant stopping treatment with thiopurines in IBD patients who need the immunosuppressants to control their disease.
More information
The U.S. National Cancer Institute has more about skin cancer prevention.
Julian White, former director of Florida A&M University's famed Marching 100 band, speaks at a news conference Monday, Nov. 28, 2011, in Tallahassee, Fla. White, who was fired by the college following the death of drum major Robert Champion, said he feels he was unfairly dismissed. Police suspect hazing contributed to Champion's death, but have not released any more details. (AP Photo/Steve Cannon)
Julian White, former director of Florida A&M University's famed Marching 100 band, speaks at a news conference Monday, Nov. 28, 2011, in Tallahassee, Fla. White, who was fired by the college following the death of drum major Robert Champion, said he feels he was unfairly dismissed. Police suspect hazing contributed to Champion's death, but have not released any more details. (AP Photo/Steve Cannon)
Julian White, former director of Florida A&M University's famed Marching 100 band, speaks with his wife Dennine at his side during a news conference Monday, Nov. 28, 2011, in Tallahassee, Fla. White, who was fired by the college following the death of drum major Robert Champion, said he feels he was unfairly dismissed. Police suspect hazing contributed to Champion's death, but have not released any more details. (AP Photo/Steve Cannon)
Julian White, center, former director of Florida A&M University's Marching 100 band, and his wife Dennine White, listen as their attorney Chuck Hobbs speaks at a news conference Monday, Nov. 28, 2011, in Tallahassee, Fla. White, who was fired by the college following the death of drum major Robert Champion, said he feels he was unfairly dismissed. Police suspect hazing contributed to Champion's death, but have not released any more details. (AP Photo/Steve Cannon)
Robert Champion Sr., left, and his wife, Pam, center, are led away from a news conference by their attorney Christopher Chestnut on Monday, Nov. 28, 2011, in Lithonia, Ga. The Champions, parents of Florida A&M drum major Robert Champion who died of suspected hazing Nov. 19, in Orlando, Fla., said they plan on filing a civil lawsuit in the matter. (AP Photo/Erik S. Lesser)
Robert Champion Sr., left, and his wife, Pam Champion, participate in a news conference on Monday, Nov. 28, 2011, in Lithonia, Ga. The Champions, parents of Florida A&M drum major Robert Champion who died of suspected hazing Nov. 19, in Orlando, Fla., said they plan on filing a civil lawsuit in the matter. (AP Photo/Erik S. Lesser)
MIAMI (AP) ? Two decades ago, the now-ousted director of the Florida A&M band warned in a letter about the dangers of hazing among the famed "Marching 100" ensemble, saying "it would be very difficult for the university and the band should someone become killed or hurt."
In the following years, however, hazing seemed to become a bigger ? if not more public ? problem. Police investigated several serious cases and students were arrested. Anti-hazing workshops were held. Dozens of band members were suspended. University officials and the marching band community were keenly aware of the persistent hazing, yet it continued and is believed to have played a role in the death this month of a 26-year-old drum major Robert Champion.
Champion's death started a blame game of sorts, with the historically black college in Tallahassee firing its band director, Julian White, accusing him of "misconduct and/or incompetence." In turn, White released more than 150 pages of documents showing that he warned the university for years about what was going on.
The chair of the Board of Governors, which oversees Florida's public universities, wrote a letter to FAMU trustees Tuesday saying they would investigate whether the university administration took appropriate action to address White's concerns.
A former band member told The Associated Press on Tuesday that White looked for ways to eradicate a culture of hazing that existed in many instrument sections of the band. White invited band members to anonymously report hazing and even had police come along on some away games, former drum major Timothy Barber told AP.
In 2001, when trumpeter Marcus Parker was paddled so severely that he ended up hospitalized with kidney damage, White had police escort the trumpet section off the field to be interrogated to show he would not tolerate hazing, Barber said.
About a dozen people pleaded guilty to a misdemeanor and received probation in that case, though it's not clear what actions, if any, the university took to punish them.
After the arrests, White approached Barber for help in getting rid of hazing. One area he focused on: A white wall in the band's practice field where nicknames for the instrument sections were prominently displayed. Becoming a member of these groups ? the clarinets were known as "The Clones" and the tubas were the "White Whales" ? meant becoming part of a tradition and a band that has played Super Bowls, the Grammys and presidential inaugurations.
But some sections had their own violent initiation rituals. White bought buckets of white paint and asked Barber to cover up the section nicknames on the wall.
"Tim, we have to find a way to eradicate these subsections of the band," Barber said White told him. "Cover the names so they see this is not something supported by the band staff."
While White documented his efforts to stop the hazing, it's possible he could've done more on the front lines, according to Richard Sigal, a retired sociology professor at County College of Morris in Randolph, N.J., who has studied hazing.
"Maybe he just had a problem that was beyond his ability to control it," Sigal said. But in general, "If the person at the top issued a zero tolerance policy for hazing and oversaw what the people under him were doing, then there was no hazing."
The details of Champion's case death are unclear. Authorities, the school and an attorney for his family said hazing played a role, but no one has been willing to shed any more light on what actually happened Nov. 19 after the football team played its rival Bethune-Cookman. Police have said only that Champion started vomiting and complained he couldn't breathe before he collapsed on a band bus outside their hotel in Orlando.
The university has announced an independent review and Gov. Rick Scott has asked state investigators to join the sheriff's department in their investigation.
University officials declined interview requests for this story, but president James Ammons, who earned his bachelor's and master's degree from FAMU, issued a statement late Tuesday.
"The university has a zero tolerance policy toward hazing. Period. But it is becoming increasingly clear that hazing continues to exist ? at FAMU and across the country at other universities, colleges and other elements ? because hazing survives and thrives in a culture of secrecy and a conspiracy of silence. I am committed to illuminating this dark corner of Florida A&M University and the American culture ... illuminating it and eradicating it."
White is fighting his dismissal, which is why he submitted the documents to the school, including dozens of suspension letters for hazing over the last decade, and communications alerting university police.
"Our incidents are few, but nevertheless hazing and harassment continues to be a problem," White wrote the then director of bands William P. Foster in 1989 after a hazing death involving a fraternity at Morehouse University. "It would be very difficult for the university and the band should someone become killed or hurt because of hazing."
In the weeks before Champion's death, White suspended 26 band members for hazing. On Nov. 17 ? just two days before Champion died ? he sent a letter to alumni, saying while most of them were positive and encouraging of former band members, some "return and perpetuate the myth of various sectional names."
"You should not return and look down on people who follow university regulations by not participating in sub-organizations," White wrote. "This is extremely important and I call on all alumni to assist the band and myself in eradicating all vestiges of hazing in the Marching '100' band .'"
Barber, who rose to head drum major and was in the band from 1996 to 2002, said he was never hazed, nor did he participate in it.
He said drum majors were like the generals of the band who tried to keep everyone in order, which makes Champion's death puzzling. At 26, Champion was likely one of the older band members because he didn't enter college until a year after high school and struggled at times to stay at the university because of his grades.
Barber in part blames alumni for not taking a stronger stand. Of about two dozen people contacted by The Associated Press, he was the first who agreed to openly speak about hazing within the band.
Barber went back to FAMU this year and practiced with Champion and the other drum majors. White told him Champion could become the head drum major. Barber also noticed the section nicknames on the white wall were still painted over.
"We need to do more," Barber said.
___
Associated Press writers Brent Kallestad and Gary Fineout in Tallahassee and legal affairs reporter Curt Anderson in Miami also contributed to this report.
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Game Day! Cards take on Maryland for in the sweet 16 of the NCAA tournament today at 5PM. The game will be live... fb.me/1un1H0ucjIl y a environ 10 heuresvia FacebookRetweeted by 14 people
Houston quarterback Matt Leinart is out for the season with a broken left collarbone, and Cleveland linebacker Scott Fujita also could be done with a broken right hand.
Pittsburgh safety Troy Polamalu, last season's NFL Defensive Player of the Year, has a suspected concussion and the team did not offer a prognosis.
The Texans lost their second quarterback in as many games; Matt Schaub broke his right foot against Tampa Bay on Nov. 13. Leinart will have surgery next week after breaking his collarbone in a win over Jacksonville.
"I've been a little bit part coach, part counselor here the last couple of weeks," coach Gary Kubiak said Monday. "I've got Schauby in my office all day last Monday and today I've got Lefty (Leinart) up there. It's just difficult. It's difficult for both of them.
"(Leinart) had been to the top of this league from the standpoint of opportunity, draft status, all that stuff. He had been there. He had been knocked down in this league. He had been told no. He was making his way back and you've got to respect that as a person and a player."
Fujita, a team leader in Cleveland, played in just nine games last season because of a left knee injury. Browns coach Pat Shurmur says Fujita will miss "a significant amount of time" and it's possible the club will place the 32-year-old on injured reserve.
"It's a big loss for us," fellow LB D'Qwell Jackson said. "You can't replace him. He makes a ton of plays. He helps me out."
Polamalu sat out almost the entire win at Kansas City following a low hit on 6-foot-6, 290-pound Chiefs tackle Steve Maneri. Coach Mike Tomlin said the team held out Polamalu as a precaution; it's the second time this season Polamalu left a game early following a blow to the head.
"I don't know at this juncture if it was a concussion, I want to be clear," Tomlin said.
Rams safety Darian Stewart was sent home Monday suffering from concussion-like symptoms, headache and dizziness. Quarterback Sam Bradford aggravated his high left ankle sprain and was sore, but coach Steve Spagnuolo was hopeful Bradford would practice Wednesday.
Redskins FB Darrel Young has a concussion and will go through tests the next couple of days. DE Stephen Bowen has a ligament tear in his left knee, but the team is hopeful he can play Sunday against the Jets.
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Titans cornerback Tommie Campbell sprained his left shoulder, but didn't dislocate the joint. Tight end Jared Cook said he passed all concussion tests after taking a hard hit against Tampa Bay. He said he wanted to return to the game, but team trainers wouldn't let him as a precaution.
Vikings long-snapper Cullen Loeffler will miss two to six weeks with a back injury. Safety Tyrell Johnson has a "significant" right hamstring injury and receiver Michael Jenkins also is having a knee injury examined. The Vikings did not say which knee Jenkins injured.
Jets defensive lineman Mike DeVito will likely not play against the Redskins after injuring his left knee against Buffalo.
"Looks like he's got a little bit of a knee, an MCL thing," coach Rex Ryan said. "I don't think Mike is going to play this week."
DeVito missed two games earlier this season with a similar injury to his right knee.
Torell Troup's nagging back troubles aren't getting any better, putting him in jeopardy of becoming the latest Bills player to go on injured reserve. Coach Chan Gailey said Troup's back locked up and prevented him from playing in a 28-24 loss at the Jets. Gailey said test results of Troup's back were "not good."
Cornerback Leodis McKelvin has a chance to play this weekend after hurting his ribs against the Jets.
Seattle placed backup linebacker and special teams standout David Vobora on injured reserve with an apparent shoulder injury. Vobora was seen in the locker room after Sunday's loss to Washington with a wrap on his left shoulder, but the team did not specify Vobora's injury.
Copyright 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Not relenting in its recent explosive launch of the "Magnum", "the only beer that pops" world's number one premium Lager brand, Heineken, is set to achieve yet another sports milestone as the brand sponsors this year's edition of the highly exciting Ikoyi Club Ladies Golf Open Championship tournament which tees off between December 1 - 2, 2011 at the prestigious Ikoyi Club 1938, Lagos. This is in addition to its sponsorship of the UEFA Champions league.
Jacqueline Van Faassen, Senior Brand Manager, Heineken said that prior to the sponsorship, Heineken has sponsored the Nigeria Cup Golf tournament and embarked on many other Golf projects in the country. However, "Heineken is a premium international brand and we have decided to associate with golf as an international sport.
''We have decided to endorse the Ikoyi Club Ladies Golf Open Championship because it is different and also helps to depict the strength that lies in women. "
She added that sports in Nigeria are going through tough times and we intend to help build the image and standard of sports through continuous support.
The two-day tourney, hosted by the Lady Golfers, Ikoyi Club 1938, is in its 37th year running and would feature lady golfers from golf clubs all over Nigeria who would participate in the tourney. On the first day of play, guests (men) and all lady golfers from handicap 0 - 36 will showcase their shot making skills while on the second day of play, only ladies of handicap 28 and below will play after which there will be a presentation of prizes at the Gala Night same day.
It would be recalled that Evelyn Oyome picked the giant trophy as overall winner of the 36th Ikoyi Ladies Open Championship last year when she outclassed other golfers and had her name engraved on the winners' podium of the club house for her remarkable feat.
Julian Edelman isn?t just a wide receiver anymore.
Edelman, who?s listed at receiver but has been spending time in the Patriots? secondary this season, has to be considered a real defensive player now that he?s laid his first hard hit on an opposing quarterback. Edelman got a couple of good shots on Eagles quarterback Vince Young on Sunday, tackling Young on a running play and later planting Young into the turf just as Young released a pass.
After the game, Edelman said taking Young to the ground was a lot of fun, but he needs to be careful about it, what with all the NFL rules protecting offensive players.
?Yeah, any time we can get a rush on the quarterback and force him to get the ball out and have our guys make the play, it feels good. And we got off the field, so that play was good,? Edelman told the Boston Herald. ?It?s funny because with all the rules floating around with regards to quarterbacks, I wanted to hit him but do it right. I just did not want to get any kind of penalty and hit him in the right zone.?
Edelman played 16 snaps, primarily covering the slot receiver, as Patriots coach Bill Belichick continues to show (as he did with Troy Brown) that if you?ve got a guy who can play slot receiver, it?s not a stretch to teach him to cover the slot receiver, too. Belichick praised Edelman after the game in Philadelphia.
?Julian?s worked hard on that,? Belichick said. ?He?s had to keep up with what?s going on on offense and also in the kicking game, but he?s worked hard. He?s spent a lot of extra time with [Patriots defensive backs coach] Josh Boyer and kind of splitting time between meetings between offense and defense, and of course he does all the special teams stuff too. He?s worked hard and he?s really been a huge help for us.?
Addex scientists discover GLP-1 induced interaction between GLP-1 and GIP receptorsPublic release date: 28-Nov-2011 [ | E-mail | Share ]
Contact: Mike Sinclair msinclair@halsin.com 44-207-318-2955 Halsin Partners
The Addex allosteric modulator platform enabled breakthrough discovery, advancing the understanding of GLP-1 mediated GPCR signaling
Geneva, Switzerland, 28 November 2011 Addex Pharmaceuticals (SIX:ADXN), a leading biopharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that its scientists have demonstrated that, in the presence of GLP-1, glucagon-like-peptide-1 receptor (GLP1R) can form a heterodimer receptor complex with gastric-inhibitory-peptide-receptor (GIPR). The discovery of this novel interaction between the two G-protein-coupled receptors (GPCR) has the potential to trigger the discovery of novel therapies for the treatment of diabetes. The findings were published online in the peer-reviewed journal Molecular Pharmacology (Lateral Allosterism in the Glucagon Receptor Family: GLP-1 Induces GPCR Heteromer Formation [Schelshorn et al., Molecular Pharmacology, Published online, doi: 10.1124/mol.111.074757]).
"GIPR and GLP1R are found together in pancreatic and nerve cells, and their roles in Type 2 diabetes make them important targets for drug development. Further research is needed to determine the pharmacological relevance of such heteromers but understanding their role may open the door to more refined therapies, particularly in metabolic disorders," explained Robert Lutjens, head of biology at Addex Pharmaceuticals and co-author of the publication. "This study demonstrates that Addex' allosteric modulation platform is a powerful tool for elucidating fundamental biological processes in addition to being the most sensitive method available for identifying allosteric modulators."
In the present study, the researchers at Addex used Bioluminescence Resonance Energy Transfer (BRET) techniques, calcium flux measurements, and microscopy to study receptor interactions within the glucagon receptor family of GPCRs. Through these techniques, a GLP-1-induced heteromer formation was exclusively observed in cells co-expressing GLP-1 with GIP receptors, but not with other receptors of the glucagon receptor subtypes. Furthermore, the pharmacology of this GLP-1-induced heteromeric receptor complex was found to be affected in presence of GIP. In addition, the heteromer's intracellular signaling through beta-arrestin or calcium second messenger was shown to be modified when compared to receptor homodimers, suggesting a form of allosteric regulation between the receptors.
"This research demonstrates how our pioneering allostery platform technology is able to observe specific interactions at the receptor level that have not been seen with conventional state-of-the-art techniques," noted Laurent Galibert, head of metabolic disease programs at Addex Pharmaceuticals. "An orally available small molecule targeting GLP1R would have a significant impact on the treatment of Type 2 diabetes. We now have the opportunity to explore and characterize this receptor further, paving the way for a better understanding of the signaling pathways implicated in diabetes and metabolism, which may offer novel therapeutic targets for allosteric modulation."
GLP-1 is an important metabolic hormone and a proven therapeutic ligand for treatment of diseases, such as Type II diabetes and obesity. Addex is leading the effort towards the development of orally available small molecule GLP1R activators, called positive allosteric modulators or PAM, which have potential to offer multiple advantages over marketed injectable peptide therapeutics targeting GLP1R.
Addex has previously disclosed that it achieved the first in vivo preclinical proof of concept demonstrating that an oral small molecule GLP1R PAM could increase the release of insulin and improve glucose control in preclinical diabetes models. Addex GLP1R PAMs are in lead generation phase for Type 2 diabetes and could become the first-in-class orally available small molecule therapeutic agents against this target.
###
Addex Pharmaceuticals (www.addexpharma.com) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase IIa clinical testing: dipraglurant (ADX48621, an mGluR5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed by our partner Janssen Pharmaceuticals Inc. to treat schizophrenia. Addex also is advancing several preclinical programs including: GABA-BR PAM for pain, overactive bladder and other disorders; mGluR4 PAM for Parkinson's, anxiety and other diseases; GLP1R PAM for Type 2 diabetes; mGluR2 NAM for treating Alzheimer's disease and depression; and FSHR/LHR NAM for sex hormone dependent tumors & reproductive system disorders. In addition, Addex has discovery programs to identify allosteric modulators of: receptor tyrosine kinase (RTK) superfamily, including TrkB PAM for treating neurodegenerative diseases (e.g. Alzheimer's, Parkinson's and Huntington's diseases); and TNF receptor superfamily, including TNFR1 NAM for inflammation (e.g. rheumatoid arthritis) and other diseases.
Chris Maggos
Business Development & Communication
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos(at)addexpharma.com
Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Pharmaceuticals Ltd, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Pharmaceuticals Ltd regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Pharmaceuticals Ltd is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.
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Addex scientists discover GLP-1 induced interaction between GLP-1 and GIP receptorsPublic release date: 28-Nov-2011 [ | E-mail | Share ]
Contact: Mike Sinclair msinclair@halsin.com 44-207-318-2955 Halsin Partners
The Addex allosteric modulator platform enabled breakthrough discovery, advancing the understanding of GLP-1 mediated GPCR signaling
Geneva, Switzerland, 28 November 2011 Addex Pharmaceuticals (SIX:ADXN), a leading biopharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that its scientists have demonstrated that, in the presence of GLP-1, glucagon-like-peptide-1 receptor (GLP1R) can form a heterodimer receptor complex with gastric-inhibitory-peptide-receptor (GIPR). The discovery of this novel interaction between the two G-protein-coupled receptors (GPCR) has the potential to trigger the discovery of novel therapies for the treatment of diabetes. The findings were published online in the peer-reviewed journal Molecular Pharmacology (Lateral Allosterism in the Glucagon Receptor Family: GLP-1 Induces GPCR Heteromer Formation [Schelshorn et al., Molecular Pharmacology, Published online, doi: 10.1124/mol.111.074757]).
"GIPR and GLP1R are found together in pancreatic and nerve cells, and their roles in Type 2 diabetes make them important targets for drug development. Further research is needed to determine the pharmacological relevance of such heteromers but understanding their role may open the door to more refined therapies, particularly in metabolic disorders," explained Robert Lutjens, head of biology at Addex Pharmaceuticals and co-author of the publication. "This study demonstrates that Addex' allosteric modulation platform is a powerful tool for elucidating fundamental biological processes in addition to being the most sensitive method available for identifying allosteric modulators."
In the present study, the researchers at Addex used Bioluminescence Resonance Energy Transfer (BRET) techniques, calcium flux measurements, and microscopy to study receptor interactions within the glucagon receptor family of GPCRs. Through these techniques, a GLP-1-induced heteromer formation was exclusively observed in cells co-expressing GLP-1 with GIP receptors, but not with other receptors of the glucagon receptor subtypes. Furthermore, the pharmacology of this GLP-1-induced heteromeric receptor complex was found to be affected in presence of GIP. In addition, the heteromer's intracellular signaling through beta-arrestin or calcium second messenger was shown to be modified when compared to receptor homodimers, suggesting a form of allosteric regulation between the receptors.
"This research demonstrates how our pioneering allostery platform technology is able to observe specific interactions at the receptor level that have not been seen with conventional state-of-the-art techniques," noted Laurent Galibert, head of metabolic disease programs at Addex Pharmaceuticals. "An orally available small molecule targeting GLP1R would have a significant impact on the treatment of Type 2 diabetes. We now have the opportunity to explore and characterize this receptor further, paving the way for a better understanding of the signaling pathways implicated in diabetes and metabolism, which may offer novel therapeutic targets for allosteric modulation."
GLP-1 is an important metabolic hormone and a proven therapeutic ligand for treatment of diseases, such as Type II diabetes and obesity. Addex is leading the effort towards the development of orally available small molecule GLP1R activators, called positive allosteric modulators or PAM, which have potential to offer multiple advantages over marketed injectable peptide therapeutics targeting GLP1R.
Addex has previously disclosed that it achieved the first in vivo preclinical proof of concept demonstrating that an oral small molecule GLP1R PAM could increase the release of insulin and improve glucose control in preclinical diabetes models. Addex GLP1R PAMs are in lead generation phase for Type 2 diabetes and could become the first-in-class orally available small molecule therapeutic agents against this target.
###
Addex Pharmaceuticals (www.addexpharma.com) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase IIa clinical testing: dipraglurant (ADX48621, an mGluR5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed by our partner Janssen Pharmaceuticals Inc. to treat schizophrenia. Addex also is advancing several preclinical programs including: GABA-BR PAM for pain, overactive bladder and other disorders; mGluR4 PAM for Parkinson's, anxiety and other diseases; GLP1R PAM for Type 2 diabetes; mGluR2 NAM for treating Alzheimer's disease and depression; and FSHR/LHR NAM for sex hormone dependent tumors & reproductive system disorders. In addition, Addex has discovery programs to identify allosteric modulators of: receptor tyrosine kinase (RTK) superfamily, including TrkB PAM for treating neurodegenerative diseases (e.g. Alzheimer's, Parkinson's and Huntington's diseases); and TNF receptor superfamily, including TNFR1 NAM for inflammation (e.g. rheumatoid arthritis) and other diseases.
Chris Maggos
Business Development & Communication
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos(at)addexpharma.com
Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Pharmaceuticals Ltd, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Pharmaceuticals Ltd regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Pharmaceuticals Ltd is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.
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According to Greg Johns of MLB.com, the funeral service for Greg Halman will be held Tuesday in the Netherlands. The family is also having a public viewing?Sunday in the Kinheim gym in Haarlem, where Halman played baseball growing up.
The Mariners plan to send?vice president of international operations?Bob Engle,?coordinator of European scouting Wayne Norton and?and Peter Van Dalen, an associate scout in the Netherlands.
Halman, who played in 44 games with the Mariners over the past two seasons, died Monday morning when he was stabbed?at an apartment in the Dutch port city of Rotterdam. According to the Associated Press, a judge has ordered Greg?s 22-year-old brother Jason to be detained for two more weeks on suspicion of murder or manslaughter. Police believe the incident may have followed an argument over loud music. Just tragic.
UofLmenssoccer 
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Public release date: 28-Nov-2011
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