给大家一个发财的机会：prous 月度分子
为什么药理的学生难找工作？其中有一个很重要的原因，药理的学生忙于实验，学技术，对药学前沿的了解少，面对研究机构或企业，在面试时不能“旁征博引”显得有学问，有知识。那还等什么呢？prous提供最前沿的新药信息，尤其是月度分子，代表新药发现的进步，大家就从这开始，拓展自己的知识面吧！利人利己，还能得银子哟评分规则说明
查到月度分子（要求：化学名或cas号，分子式，药理概述）奖励财富20
译成中文者根据翻译字数的多少，质量的高低再奖励1-5威望 先举个例子：如 January 2007
SUGAMMADEX SODIUM
THERAPEUTIC CLAIM reversal agent for neuromuscular blocking agents
CHEMICAL NAMES
1)r-Cyclodextrin, 6A,6B,6C,6D,6E,7F,6G,6H-octakis-S-(2-carboxyethyl)-6A,6B,6C,6D,6E,7F,6G,6H-octathio , octasodium salt
2) Octasodium 6,6',6'',6''',6'''',6''''',6'''''',6'''''''-octakis-S-(2-carboxylatoethyl)-6,6',6'',6''',6'''',6''''',6'''''',6'''''''-octathiocyclo--(14)-D-octaglucopyranoside
MOLECULAR FORMULA C72H104Na8O48S8
MOLECULAR WEIGHT 2178
CAS REGISTRY NUMBER 343306-79-6
Sugammadex sodium, a reversal agent used during general anesthesia, is the first selective relaxant binding agent (SRBA), a drug-specific cyclodextrin that is specifically designed to reverse the effects of the muscle relaxant rocuronium bromide (Esmeron 我觉得面试的时候，不仅仅考察个人的专业知识,更重要的看中你这个人怎么样?
遇到困难怎么办?承受压力有多大,沟通交流能力有多少,而不仅仅是专业知识 Zileuton 1997-Jan
CHEMICAL NAMES
N-Hydroxy-N-[1-(benzothiophen-2-yl)ethyl]urea;
(N-Hydroxy-N-[1-(benzo[b]thien-2-yl)ethyl]urea;
(1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
Zileuton, ABT-077, A-64077, Zyflo, Leutrol
MOLECULAR FORMULA C11-H12-N2-O2-S
MOLECULAR WEIGHT 236.2938
CAS REGISTRY NUMBER 111406-87-2
Zileuton is a selective, orally active inhibitor of 5- lipoxygenase (5-LO) from Abbott, proven to exert antiinflammatory and antiallergic effects in animal models and humans. The FDA cleared zileuton (Zyflo[TM]) for the prevention and chronic treatment of asthma in patients at least 12 years of age in December, and Abbott launched it on January 28th (Abbott News Release).
齐留通是雅培公司生产的一种高选择性，口服有效的5-脂氧合酶抑制剂的，被证明在动物和临床实验模型中有抗炎和抗过敏作用。美国食品与药物管理局在12月声明齐留通可以用来预防和长期治疗12岁以上的哮喘，雅培公司于1月28日将此药物推向市场。 September 2007
[size=4][color=#FF0000]Plerixafor hydrochloride[/color][/size]
[img]http://www.prous.com/images/moleculas/196024.gif[/img]
The chemokine CXCR4 (SDF-1) antagonist plerixafor hydrochloride (AMD-3100, Mozobil™) is in phase III clinical development at Genzyme, which acquired the product through its acquisition of AnorMED in late 2006. AnorMED had been developing plerixafor for the treatment of HIV, but discontinued the trials in 2001 due to abnormal cardiac activity and lack of efficacy.
By blocking CXCR4, a specific cellular receptor, plerixafor triggers the rapid movement of stem cells out of the bone marrow and into circulating blood, where they can be collected for use in stem cell transplant. The current standard of care for stimulating the mobilization of stem cells from the bone marrow is with granulocyte colony-stimulating factor (G-CSF). Plerixafor is being developed in combination G-CSF as a novel stem cell mobilization regimen in patients undergoing stem cell transplantation for the treatment of non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). The trials are designed to evaluate the ability of plerixafor plus G-CSF to rapidly increase the number of peripheral blood stem cells capable of engraftment, thereby increasing the proportion of patients reaching a peripheral blood stem cell target and, as a result, reducing the number of apheresis sessions required for patients to collect a target number of peripheral blood stem cells.
In July, Genzyme announced that it had successfully completed a first phase III trial of plerixafor in non-Hodgkin's lymphoma, and that the trial had met its primary and secondary endpoints. The randomized, double-blind, placebo-controlled trial examined the effectiveness of plerixafor in increasing the number of hematopoietic stem cells collected for a transplant in 298 patients undergoing a hematopoietic stem cell transplant (HSCT) for NHL at medical centers in the U.S. and Canada. The study compared the hematopoietic stem cell yields from patients treated with plerixafor plus G-CSF to patients treated with G-CSF in combination with placebo. In the primary efficacy endpoint, 59% of patients treated with plerixafor/G-CSF achieved the target threshold for collection of at least 5 million CD34+ cells/kg from the peripheral blood with 4 or fewer days of apheresis sessions, compared with 20% of patients in the G-CSF/placebo group. The three-fold increase was highly statistically significant in favor of the study drug. The 40% absolute difference between the two treatment groups was nearly double the target that Genzyme had prospectively defined in the protocol for the study, which was reviewed by the FDA as part of the Special Protocol Assessment (SPA) process. In the secondary efficacy endpoint, nearly 87% of patients treated with plerixafor/G-CSF achieved the minimum level of stem cells generally associated with a successful transplant in 4 or fewer days of apheresis sessions, compared with approximately 47% in the placebo arm. The other secondary efficacy endpoints were supportive of these findings, including number of days needed to reach target ranges for stem cell mobilization, success of engraftment, number of days needed to engraft and durability of the engraftment for the first 100 days.
A few weeks later, Genzyme announced similar positive results from a separate phase III trial comparing plerixafor/G-CSF to G-CSF/placebo for stem cell mobilization prior to autologous HSCT in patients with multiple myeloma. Similar to the NHL results above, plerixafor was shown to enable 72% of patients to achieve target thresholds for stem cell collection (≥ 6 million CD34+ cells/kg) from peripheral blood with two days or fewer of apheresis sessions, as compared to only 34% of patients in the G-CSF/placebo group. The study's secondary outcomes were also met, showing a statistically significant result in favor of plerixafor in the number of patients reaching the target threshold within 4 days of apheresis, and the number of patients who reached at least 2 million cells collected in 4 days. Other secondary outcomes were also supportive, including success of engraftment, number of days needed for engraftment, and durability of engraftment for the first 100 days. The trial also robustly met the primary endpoint specified by EMEA, which is a composite of successful mobilization and engraftment. The study drug was well tolerated in both trials.
Based on these results, Genzyme expects to file for U.S. and European approval in both the lymphoma and multiple myeloma indications in the first half of 2008. Plerixafor has been granted SPA and orphan drug status in the U.S. and the E.U., and the pivotal trials have undergone special protocol assessment by the FDA and protocol assistance by the EMEA. August 2007
[size=4][color=#FF0000]Dimebolin hydrochloride[/color][/size]
[img]http://www.prous.com/images/moleculas/398997.gif[/img]
Dimebolin hydrochloride (Dimebon™) is an orally-available, small-molecule agent that is in clinical testing for the treatment of Alzheimer's and Huntington's diseases-two progressive, devastating conditions with limited treatment options. Based on clinical and preclinical data generated to date, developer Medivation believes that dimebolin operates via a novel mechanism of action and may exert a neuroprotective effect in multiple areas of the central nervous system. Dimebolin appears to block a new target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. Dimebolin also blocks both cholinesterase and the NMDA receptor simultaneously. These two targets provide the mechanism of action for all FDA-approved drugs for Alzheimer's disease, although no marketed drug is known to have an effect on both pathways.
In July, the Huntington Study Group (HSG) reported that recruitment of participating sites for the DIMOND phase II trial (ClinicalTrials.gov identifier: NCT00497159), which will evaluate dimebolin in subjects with mild to moderate Huntington's disease (HD), is currently in progress. The randomized, double-blind, placebo-controlled phase II trial will enroll up to 90 patients at some 15 research centers in the U.S. and U.K. It is designed to evaluate the safety and tolerability of dimebolin during three months of treatment, as well as its effects on cognition, motor signs and overall functioning of HD patients aged 18 years or older. Patient enrollment will begin during the summer of 2007.
In June, the company reported that benefits of dimebolin hydrochloride over placebo in a double-blind, placebo-controlled phase II study in mild to moderate Alzheimer's disease (AD) were statistically significant on all five study endpoints at 12 months. In the multicenter, double-blind trial, 183 patients with mild to moderate AD were randomized to oral dimebolin (60 mg/day) or placebo for six months. Of these patients, 134 subsequently consented to continue treatment for up 12 months in their same treatment group. On the primary endpoint, the ADAS-cog, dimebolin caused an improvement over placebo of 6.9 points at one year. On the global function endpoint used in this study, the CIBIC-plus, dimebolin's benefit over placebo was 0.8 points at 12 months. Global function improved or remained stable in 69% of treated Alzheimer's disease patients after one year of dimebolin therapy. Dimebolin produced an aggregate benefit over placebo in this study that was larger at 12 months than at six. After a year of treatment, dimebolin's benefit over placebo was greater than six-month levels on the ADAS-cog (6.9 points vs. 4.0 points), CIBIC-plus (0.8 points vs. 0.6 points), and ADCS-ADL (5.2 points vs. 2.9 points) scales; however, only the ADAS-cog difference reached statistical significance. Dimebolin's benefit over placebo on the other two endpoints (the Mini Mental State Exam, [MMSE] and the Neuropsychiatric Inventory [NPI]) at six months was maintained at one year. Dimebolin-treated patients experienced significantly fewer serious adverse events than placebo-treated patients (3.4% vs. 11.7%). The most frequent adverse events associated with treatment were dry mouth, depressed mood/depression and sweating. Six-month phase III studies of dimebolin in AD will begin next year.
Dimebolin hydrochloride, which also acts as an antihistamine, is marketed in Russia by the Russian Academy of Sciences for the treatment of skin allergy and allergic rhinitis. 呵呵我还没有来得及翻译呢
就已经评分了啊 Strontium Ranelate march 2007
Strontium ranelate, a promising new osteoporosis therapeutic in late-stage development at Servier, is the first agent to stimulate the formation of new bone as well as prevent loss of existing bone, and therefore represents a major advance in the treatment of this highly prevalent disease. Unlike existing therapies, for osteoporosis all of which are designed to limit the loss of existing bone (antiresorptive agents), strontium ranelate has anabolic effects and thus is doubly effective in increasing bone strength and density.
The results of two major randomized, double-blind, placebo-controlled long-term studies support the efficacy of strontium ranelate in osteoporosis. STRATOS (STRontium Administration for Treatment of Osteoporosis) and PREVOS (PREVention of Osteoporosis Study) were two-year studies carried out to assess the minimum active doses of strontium ranelate required for the treatment and prevention of bone loss in postmenopausal women. STRATOS enrolled 353 postmenopausal women with at least one previous vertebral fracture and lumbar bone mineral density (BMD) T-score < -2.4 who were randomized to treatment for two years with placebo or strontium ranelate (0.5, 1 or 2 g/day). All patients also received daily supplements of calcium and vitamin D2. In the PREVOS trial, 160 healthy early postmenopausal women were randomized to treatment with placebo or strontium ranelate (0.125, 0.5 or 1 g/day) for one year, in addition to daily calcium supplements. Following final analysis of STRATOS and PREVOS, the investigators concluded that the dose of 2 g/day strontium ranelate provided the best efficacy-safety ratio for the curative treatment of postmenopausal osteoporosis, while a dose of 1 g/day was optimum for the prevention of bone loss in early postmenopausal women.
Further data are awaited from the ongoing five-year TROPOS (TReatment Of Peripheral Osteoporosis) and SOTI (Spinal Osteoporosis Therapeutic Intervention) trials. These two multinational, prospective, randomized, double-blind, placebo-controlled studies are evaluating the therapeutic efficacy of strontium ranelate at a dose of 2 g/day in the treatment of severe osteoporosis in postmenopausal women. SOTI is assessing the drug's ability to reduce new vertebral fractures in women with low BMD and a history of at least one vertebral fracture, and TROPOS is assessing its effects on reducing the incidence of peripheral fractures. The effects of strontium ranelate on incidence of new hip fractures will be pooled from the two studies.
Servier is conducting European phase III trials evaluating the efficacy of strontium ranelate (Protos(TM)) for both treatment and prevention of osteoporosis. Fujisawa has obtained rights to develop, manufacture and market strontium ranelate for the Japanese market, where phase I studies are now under way. 在我们这里药理的做实验不多啊
还是我们药化的忙的要死 [s:123] October 2007
[size=4][color=#FF0000]Sugammadex sodium [/color][/size]
[img]http://www.prous.com/images/moleculas/306386.gif[/img]
Sugammadex sodium, a reversal agent used during general anesthesia, is the first selective relaxant binding agent (SRBA), a drug-specific cyclodextrin that is specifically designed to reverse the effects of the muscle relaxant rocuronium bromide (Esmeron July 1998
[size=4][color=#FF0000]Abacavir succinate [/color][/size]
[img]http://www.prous.com/images/moleculas/213610.gif[/img]
In June 1998 Glaxo Wellcome submitted an NDA for its anti-HIV drug abacavir succinate (Ziagen™, formerly 1592U889) to the FDA seeking approval for both pediatric and adult dosage forms. Abacavir is a nucleoside reverse transcriptase inhibitor that appears to have superior antiviral activity compared to other drugs in this class. Ziagen™ has been designated a fast track product by the FDA. The company also submitted abacavir for approval in the European Union. Almost 8,000 HIV-infected patients have been treated with abacavir and the company has submitted comprehensive data including various patient opulations and various combinations. March 2001
[size=4][color=#FF0000]ACE2: An attractive new target for cardiovascular drug discovery[/color][/size]
[img]http://www.prous.com/images/moleculas/296766.gif[/img]
Angiotensin converting enzyme (ACE) is produced in the endothelium of somatic tissues and is a pivotal member of the renin-angiotensin system. It mediates various local and systemic effects within the cardiovascular system by removing the carboxy terminal dipeptide from the decapeptide Ang I to generate Ang II. Blockade of ACE normalizes abnormally high systemic vascular tone, reversed cardiac myocyte hypertrophy and fibrosis. Captopril, the original member of the ACE-inhibitor class, was introduced in 1980 and has become a classic in the field of rational drug design. Nearly 20 ACE inhibitors are now available for clinical use. ACE inhibitors are recommended as first-line treatment for hypertensive patients with type 1 diabetes or with diabetic nephropathy due to their favorable effects on renal function. They are also used in the treatment of heart failure. ACE inhibitors are generally safe and well tolerated, with persistent dry cough as the most troublesome side effect.
In the search for an improved ACE inhibitor, scientists at Millennium have conducted a genomics-based search for the gene determining why some patients respond better than others to this widely used class of antihypertensive agents. They discovered a variant of the gene encoding ACE which they designated ACE2. This gene is the subject of a recently issued U.S. patent (US 6194556). Unlike ACE, which is expressed ubiquitously throughout the vasculature, ACE2 is expressed only in cardiac, renal and testicular cells. The ACE2 protein has regions of substantial homology to ACE and, like the latter, has been confirmed to cleave Ang I and other key vasoactive peptides. However, the activity of ACE2 is distinct. This was confirmed by tests demonstrating that neither lisinopril nor captopril was capable of blocking ACE2 conversion of Ang I. Millennium then identified a series of molecules acting as specific ACE2 inhibitors and, in collaboration with Lilly, has begun preclinical testing with the objective of developing a candidate drug for the treatment of hypertension and congestive heart failure. The structure of a representative ACE2 inhibitor is shown.
Put information about Arterial Hypertension into context with the Prous Science Drug R&D Backgrounders, a new series of continuously updated, disease-focused reports published on the internet. Follow this link to learn more about this invaluable, unique new resource and to request a free trial password. October 2002
[size=4][color=#FF0000]Adefovir dipivoxil [/color][/size]
[img]http://www.prous.com/images/moleculas/196738.gif[/img]
In September 2002, Gilead's adefovir dipivoxil (Hepsera™) became the first nucleotide analogue to be approved by the FDA for the treatment of chronic hepatitis B (HBV). The specific approved indication for the drug is the oral treatment of chronic HBV in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Adefovir blocks the replication of the hepatitis B virus through inhibition of viral enzymes. In clinical studies, it has provided significant improvement in liver histology and fibrosis, reductions in serum HBV DNA levels, increased rates of seroconversion and normalization of ALT levels compared to placebo in both treatment-naive patients and those previously treated with interferon. Adefovir dipivoxil is the first drug with demonstrated efficacy in hepatitis B "e" antigen (HBeAg)-negative, or precore mutant, patients. Significantly, it has also proved effective in patients who are resistant to lamivudine, the only other viral enzyme inhibitor currently on the market, and in patients co-infected with HIV. To date, no adefovir dipivoxil associated resistance mutations have been identified in patients treated up to 136 weeks. Manufacturer Gilead has also submitted an MAA in the E.U., which is currently under review. Nov 1999
[size=4][color=#FF0000]AG-7088 [/color][/size]
[img]http://www.prous.com/images/moleculas/268306.gif[/img]
[size=4]Preliminary clinical results reported for first rhinovirus 3C protease inhibitor[/size]
AG-7088 is a new rhinovirus 3C protease inhibitor undergoing early clinical development at Agouron Pharmaceuticals, Inc. (Warner-Lambert Co.) for the treatment of human rhinoviral infection. Company researchers presented preliminary clinical safety and pharmacokinetic data on the drug at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held September 26-29, 1999, in San Francisco.
Intranasal AG-7088 was evaluated in double-blind, placebo-controlled, parallel trials in healthy volunteers following either single doses (4 or 8 mg; 12 subjects) or multiple doses (4 or 8 mg six times daily for seven days; 24 subjects) of 100 or 200 mcl sprayed into the nostrils. No clinically relevant changes in safety parameters or serious side effects were reported. AG-7088 was detected in only two of eight subjects following single doses and transient, low levels of the drug were measured in three of 12 subjects receiving multiple doses. In contrast, plasma levels of the acid metabolite AG-7185 were measured in seven of eight subjects for up to eight hours after single doses, with no accumulation upon repeated dosing (Pithavala, Y.K. et al. 39th Intersci Conf Antimicrob Agents Chemother [Sept. 26-29, San Francisco] 1999, Abst H-275). 格式很标准吧？呵呵多给点分咯~~ [s:64] [s:110] [s:80] [s:109] 药理,哎,可怜的药理 迷糊,好难,大多是英文 Jan. 2008
Obatoclax mesylate
Obatoclax mesylate (GX15-070) is a small-molecule indole bipyrrole drug compound and pan-Bcl-2 family inhibitor being developed at Gemin X Biotechnologies for the treatment of cancer. Recently published studies have confirmed the mechanism of action of the compound, demonstrating that it specifically disrupts the survival of cancer cells as a result of inhibiting the Bcl-2 pro-survival protein Mcl-1. Elevated expression of members of the Bcl-2 pro-survival family of proteins can confer resistance to apoptosis in cancer cells, and obatoclax overcomes Bcl-2 pro-survival proteins' resistance to the pro-apoptotic proteins BAX and BAK. The anti-apoptotic protein Mcl-1 plays a particularly central role in conferring cancer cell resistance in certain instances, and obatoclax potently interferes with the direct interaction between Mcl-1 and BAK in the intact mitochondrial outer membrane and inhibited the association between Mcl-1 and BAK in intact cells. It is thought that Mcl-1 regulates BAK within the mitochondrial outer membrane (Nguyen, M. et al. Proc Natl Acad Sci USA 2007, 104(49): 19512).
During the recent annual meeting of the American Society of Hematology, results were presented from several preclinical and clinical studies evaluating obatoclax. Obatoclax inhibited cell proliferation and induced apoptosis in drug-resistant non-Hodgkin's B-cell lymphoma cell lines, including those resistant to rituximab. No cytotoxicity was seen with obatoclax in human peripheral blood leukocytes from different donors (Martinez-Paniagua, M.A. et al., Abst 1402). Experiments in chronic lymphocytic leukemia cells showed that increased levels of phosphorylated Bcl-2 reduced obatoclax cytotoxic activity. The synergistic activity seen with obatoclax and bortezomib was also regulated by Bcl-2 phosphorylation, and combination with ERK inhibitors showed potential in increasing the activity of the compound (Galan, P.P. et al., Abst 3464).
A phase I study was conducted in patients with relapsed or refractory mantle cell lymphoma to evaluate the combination of obatoclax and bortezomib. The dosage selected for further assessment was 45 mg/1.3 mg/m2, administered i.v. on days 1, 4, 8, and 11 of a 21-day cycle which displayed acceptable tolerability. Evidence of activity was seen (Goy, A. et al., Abst 2569). Prolonged infusions of obatoclax were assessed in patients with hematological malignancies enrolled in a phase I trial, with 21 patients receiving obatoclax 20-28 mg/m2/day weekly or 20 mg/m2/day for 2, 3 or 4 consecutive days every 2-3 weeks. Multiple-day infusions were well tolerated. A patient with acute myelogenous leukemia achieved a cytogenetic complete response with complete hematological recovery and transfusion independence on day 9 after starting weekly obatoclax infusions (Schimmer, A.D., Abst 892).
Obatoclax is currently being evaluated in a phase II trial in patients with chronic idiopathic myelofibrosis (CIMF). Patients are given a dose of 60 mg by 24-hour infusion every 2 weeks. In 14 patients with data available after administration of 102 cycles, grade 3 adverse events included peripheral edema, dyspnea, fatigue, diarrhea and chest pain. Plasma obatoclax concentrations appeared to reach steady state before the end of the infusion. Of 8 previously treated patients, 2 had a Clinical Improvement Response lasting 6 months with increases in hemoglobin and red blood cell transfusion independence while continuing chronic recombinant erythropoietin therapy to which they had not previously responded. Of 6 previously untreated patients, 3 were still on therapy with stable disease at the time results were reported (Verstovsek, S. et al., Abst 3553).
Obatoclax is also undergoing phase II clinical evaluation for the treatment of Hodgkin's lymphoma, myelofibrosis with myeloid metaplasia, myelodysplasia and follicular lymphoma. Early clinical studies are also under way for the treatment of chronic lymphocytic leukemia (CLL), chronic myeloid leukemia, acute myeloid leukemia, relapsed or refractory non-small cell lung cancer, relapsed or refractory mantle cell lymphoma and solid tumors. The NCI is conducting studies of obatoclax in combination with topotecan in patients with relapsed or refractory small cell lung cancer and solid tumors. Obatoclax was granted orphan drug designation by the FDA in 2004 for the CLL indication. 好活动，支持
页:
[1]
