有奖活动 在研新药
发布正在研发的有前景的新药内容包括：
新药名称
研发部门
作用简要机理
研发阶段
不一定全部包括以上内容，对于发帖者 给予重奖 10-200鸭币 非常优秀者1-5威望 Drug Name World Status Pharma Status
FK-778 Discontinued Ceased
malononitrilamides
MNAs, Astellas
MNAs, Sanofi-Aventis
Latest Change
Updated On By Latest Change
29 Aug 2006 IL Discontinuation reported
Company Status Data
Originator Country Development Stage
Astellas Japan Discontinued
Activity Data
Therapy Description Code Status
Immunosuppressant I5 Discontinued
Dermatological D11Z Discontinued
Anticancer, immunological K3 Discontinued
Antiarthritic, immunological M2C Discontinued
Neurological N11Z Discontinued
Pharmacology Description Code
Hydroorotate dehydrogenase inhibitor DH-HYO-
Tyrosine kinase inhibitor KI-TYR-
Therapy Code Pharmacology Code
I5
D11Z
K3
M2C
N11Z DH-HYO-, KI-TYR-
DH-HYO-, KI-TYR-
DH-HYO-, KI-TYR-
DH-HYO-, KI-TYR-
DH-HYO-, KI-TYR-
Route of Administration Route of Administration Code
Alimentary, po A-PO
Indication Status
Transplant rejection, general Discontinued
Chemical Data
Origin of Material Code Description
CH-SY Chemical, synthetic
CAS Registry Number Molecular Weight Molecular Formula
Country Data
Country Name Status Year Launched Licensing Op.
Argentina - No
Australia - No
Austria - No
Belgium - No
Brazil - No
Canada - No
Chile - No
China - No
Colombia - No
Denmark - No
Finland - No
France - No
Germany Preclinical No
Greece - No
Hong Kong - No
India - No
Ireland - No
Israel - No
Italy - No
Japan Preclinical No
Luxembourg - No
Malaysia - No
Mexico - No
Netherlands - No
New Zealand - No
Norway - No
Peru - No
Philippines - No
Portugal - No
Russian Federation - No
South Africa - No
South Korea - No
Spain - No
Sweden - No
Switzerland - No
Thailand - No
Turkey - No
UK - No
USA Preclinical No
Venezuela - No
Major Events
Event Date Act/Est Event Details
29 Jul 2006 Est Discontinued Products Phase II Clinical Trial, Efficacy
30 Jun 2006 Est Status Reversion Preclinical
15 Jun 2004 Est New Therapeutic Activity Vasoprotective, systemic (C5C)
15 Jun 2004 Est Pharmacology Identified Hydroorate dehydronase and Tyrosine kinase inhibitors
23 Sep 2003 Est New Therapeutic Activity Antiviral, other (J5Z)
22 Jan 2002 Act New Indication Transplant rejection, general
22 Jan 2002 Act Compounds Identified malononitrilamides
22 Jan 2002 Act Change in Status Phase II Clinical Trial
20 Jan 2000 Est Change in Licensee Status Fujisawa, Phase I Clinical Trial
13 Jul 1999 Est New Product in Pharmaprojects
Ratings
Novelty Market Size Speed Total
Not available (0) US$ 501-2000 million (2) Not available (0) Not available
Detailed Information
Astellas has discontinued development of FK-778, the lead in a series of synthetic malononitrilamides (MNAs) for the treatment of organ transplant rejection, as it was not superior to existing treatments in Phase II trials (Company Web Page, Astellas, 11 Aug 2006). It was originally licensed from Sanofi-Aventis (Aventis before the merger; previously Hoechst Marion Roussel), which licensed all rights to Astellas. It is derived from the active metabolite of leflunomide (qv), A77,1726. It inhibits T- and B-cell function via the inhibition of dihydroortic acid dehydrogenase and tyrosine kinase (Transplantation, 2004, 77, S88).
Marketing
Astellas (Fujisawa before the merger) had exclusive worldwide rights to develop MNAs for transplantation, dermatological and certain autoimmune diseases (excluding multiple sclerosis), Sanofi-Aventis retained rights for oncology, rheumatology and CNS indications (Press release, Fujisawa, 12 Jul 1999; Direct communication, Fujisawa, 26 Apr 2000; Scrip Daily Online, 10 Jul 2001, S00717640).
Clinical
Phase II
In a controlled, double-blind, randomized European Phase II trial, 149 renal-transplant recipients received 1/3 treatment arms: high-level FK-778 + tacrolimus (qv) + steroids; low-level FK-778 + tacrolimus + steroids; placebo + tacrolimus + steroids. High- and low-dose active treatment arms reduced the incidence of acute rejection by 12.6 and 13.2%, respectively cf placebo. Side-effects were comparable between all arms, with dose-related anaemia being the most frequently reported adverse event (Transplantation, 2004, 77, S88). It was in a pan-European, dose-finding Phase IIb study, European Phase II trials of FK-778 + tacrolimus for prophylaxis of liver transplant rejection and Phase II trials in liver and kidney transplant rejection in the US (Company pipeline, Fujisawa, 30 Oct 2002 & 25 Feb 2004; Press release, Fujisawa, 23 Sep 2003).
Phase I
In completed European and US single- and repeat-dose Phase I trials, dose-limiting adverse events were not seen in escalating single-doses and repeat-doses up to 1100 and 200mg/day, respectively. Bioavailability was unaffected by food and there were no gender differences in pharmacokinetics.
Preclinical
In the rat model of chronic renal-allograft rejection, FK-778 x10 days resulted in a dose-dependent decrease in proteinuria and serum creatinine levels during 90 day follow-up, cf control. In transplant models in rodents, dogs and primates, there was significantly less chronic allograft nephropathy changes in FK-778-treated animals, cf controls. In addition, it decreased intragraft mononuclear cell infiltration and serum allospecific IgG and IgM production, and intragraft transforming growth factor-β mRNA expression. In rats, FK-778 prevented nonimmune intimal vascular injury, by a mechanism independent of immunosuppression, linked to tyrosine kinase inhibition, possibly by inhibition of platelet-derived growth factor (PDGF) (Transplantation, 2004, 77, S88). In in vitro and animal studies, FK-778 inhibited virion assembly of cytomegalovirus and polyoma virus. It also blocked cellular and humoural immune responses (Press release, Fujisawa, 23 Sep 2003). Updated by IL on 29/8/2006. Drug Name World Status Pharma Status
U3-1287 Preclinical Active
Latest Change
Updated On By Latest Change
21 Jul 2006 PD Clinical plans reported
Company Status Data
Originator Country Development Stage
U3 Pharma Germany Preclinical
Licensee
Amgen USA Preclinical
Activity Data
Therapy Description Code Status
Monoclonal antibody, human T3A2 Preclinical
Anticancer, immunological K3 Preclinical
Pharmacology Description Code
Tyrosine kinase inhibitor KI-TYR-
Therapy Code Pharmacology Code
T3A2
K3 KI-TYR-
KI-TYR-
Route of Administration Route of Administration Code
Unknown UN
Indication Status
Unspecified Preclinical
Chemical Data
Origin of Material Code Description
BI-P-A Biological, protein, antibody
CAS Registry Number Molecular Weight Molecular Formula
Country Data
Country Name Status Year Launched Licensing Op.
Argentina - No
Australia - No
Austria - No
Belgium - No
Brazil - No
Canada - No
Chile - No
China - No
Colombia - No
Denmark - No
Finland - No
France - No
Germany Preclinical No
Greece - No
Hong Kong - No
India - No
Ireland - No
Israel - No
Italy - No
Japan - No
Luxembourg - No
Malaysia - No
Mexico - No
Netherlands - No
New Zealand - No
Norway - No
Peru - No
Philippines - No
Portugal - No
Russian Federation - No
South Africa - No
South Korea - No
Spain - No
Sweden - No
Switzerland - No
Thailand - No
Turkey - No
UK - No
USA Preclinical No
Venezuela - No
Major Events
Event Date Act/Est Event Details
21 Jul 2006 Act Development Continuing
16 Feb 2006 Act No Development Reported
12 Oct 2004 Est Pharmacology Identified Tyrosine kinase inhibitor (KI-TYR-)
12 Oct 2004 Est Development Continuing
12 Aug 2004 Act No Development Reported
11 Jun 2002 Act New Therapeutic Activity Monoclonal antibody, human (T3A2)
11 Jun 2002 Act New Licensees Abgenix
10 Jun 2002 Act New Product in Pharmaprojects
Ratings
Novelty Market Size Speed Total
All Preclinical (1) US$ 2001-5000 million (3) Development not started (1) Not available
Detailed Information
U3-1287 is a fully-human MAb targeting a membrane-bound receptor tyrosine kinase (RTK) under development by U3 Pharma for the treatment of cancer (12th BioPartner Eur (London), 2004).
Marketing
U3 Pharma has a co-development and commercialization agreement with Abgenix (now Amgen) (Direct communication, Abgenix, 29 Apr 2003; Company Web Page, U3 Pharma, 15 Oct 2004).
Clinical
Clinical development is planned for 2007.
Preclinical
It has shown involvement in breast, lung and colorectal cancers (Company Web Page, U3 Pharma, 21 Jul 2006). It is in in vivo efficacy studies (12th BioPartner Eur (London), 2004). Updated by PD on 21/7/2006. Drug Name World Status Pharma Status
M-40403 Phase II Clinical Trial Active
M-40404
M-40470
SOD mimetics, ActivBiotics
Latest Change
Updated On By Latest Change
16 Jan 2006 CR Merger of ActivBiotics with MetaPhore Pharmaceuticals reported
Company Status Data
Originator Country Development Stage
ActivBiotics USA Phase II Clinical Trial
Activity Data
Therapy Description Code Status
Analgesic, other N2Z Phase II Clinical Trial
Anticancer, other K6Z Phase II Clinical Trial
Antiarthritic, other M2Z Preclinical
Neuroprotective N7C Preclinical
Septic shock treatment B6A Preclinical
Symptomatic antidiabetic A10C Preclinical
Antiasthma R8A Preclinical
GI inflammatory/bowel disorders A16 Preclinical
Pharmacology Description Code
Superoxidase dismutase-2 stimulant SOD-2+
Therapy Code Pharmacology Code
N2Z
K6Z
M2Z
N7C
B6A
A10C
R8A
A16 SOD-2+
SOD-2+
SOD-2+
SOD-2+
SOD-2+
SOD-2+
SOD-2+
SOD-2+
Route of Administration Route of Administration Code
Parenteral, intravenous P-IV
Alimentary, po A-PO
Indication Status
Pain, post-operative Phase II Clinical Trial
Pain, cancer Phase II Clinical Trial
Cancer, renal Phase II Clinical Trial
Cancer, melanoma Phase II Clinical Trial
Pain, neuropathic Phase II Clinical Trial
Chemical Data
Origin of Material Code Description
CH-SY Chemical, synthetic
CAS Registry Number Molecular Weight Molecular Formula
479.36 C21H31Cl2MnN5
Chemical Name
Dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5,6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-1,7-nitrilo-7H-dibenzo[b,h] [1,4,7,10]tetraazacyclo-heptadecine-kappaN5,kappaN13,kappaN18,kappaN21,kappaN22]manganese
Structure
Patent Data
Country Number Priority Country Priority Date
US 6180620 US 9 April 1998
Country Data
Country Name Status Year Launched Licensing Op.
Argentina - Yes
Australia - Yes
Austria - Yes
Belgium - Yes
Brazil - Yes
Canada - Yes
Chile - Yes
China - Yes
Colombia - Yes
Denmark - Yes
Finland - Yes
France - Yes
Germany - Yes
Greece - Yes
Hong Kong - Yes
India - Yes
Ireland - Yes
Israel - Yes
Italy - Yes
Japan - Yes
Luxembourg - Yes
Malaysia - Yes
Mexico - Yes
Netherlands - Yes
New Zealand - Yes
Norway - Yes
Peru - Yes
Philippines - Yes
Portugal - Yes
Russian Federation - Yes
South Africa - Yes
South Korea - Yes
Spain - Yes
Sweden - Yes
Switzerland - Yes
Thailand - Yes
Turkey - Yes
UK - Yes
USA Phase II Clinical Trial Yes
Venezuela - Yes
Major Events
Event Date Act/Est Event Details
23 May 2005 Est New Indication Pain, neuropathic
29 Sep 2004 Est New Indication Pain, cancer
14 Jul 2003 Est Licensing Opportunities Worldwide
13 Jun 2003 Est Change in Status Phase II Clinical Trial
12 Jul 2002 Est New Therapeutic Activity Antiasthma (R8A) and Antipruritic/inflamm, allergic (D4A)
21 Jan 2002 Est New Therapeutic Activity Cardiovascular (C9Z)
28 Aug 2001 Act New Therapeutic Activity Symptomatic antidiabetic (A10C)
31 May 2001 Act Change in Status Phase I Clinical Trial
21 Feb 2001 Act New Patent Applications US6180620
6 Jul 2000 Act New Chemical Structure New
13 Dec 1999 Est Compounds Identified SOD mimetics, Metaphore
20 Oct 1999 Est New Product in Pharmaprojects
Ratings
Novelty Market Size Speed Total
Leading Compound (6) US$ 5001-10000 million (4) Slower than Average (2) 12
Detailed Information
M-40403 is an iv and po manganese-based stable superoxide dismutase (SOD) mimetic, under development by MetaPhore (ActivBiotics) for the treatment of inflammation, pain, rheumatoid arthritis (RA), cancer, stroke and diabetic neuropathy (Press release, MetaPhore, 18 Sep 2000; Company Web Page, MetaPhore, 14 Jan 2004). It may also reduce dose-limiting IL-2-induced hypotension. Other compounds in the series are in development for the treatment of pain, and for HIV and reperfusion injury (M-40419 and M-40401; both qv). Topical and PEGylated formulations of M-40403 (both qv) are also under development.
Marketing
An NDA filing was expected in the 4th qtr of 2005 (JP Morgan 22nd Ann Healthcare Conf (San Francisco), 2004). MetaPhore was awarded 4 SBIR grants by the NIH, to fund research into the use of SOD mimetics (Press releases, MetaPhore, 18 Sep 2000 & 19 Nov 2001).
Clinical
Phase II
It is in a randomized, double-blind, placebo-controlled Phase II trial in combination with opioids in moderate-to-severe cancer pain. The primary objective is to evaluate the analgesic effect of M-40403 in combination with prescribed pain medication (Press release, MetaPhore, 29 Sep 2004; BioVenture View Daily Online, 4 May 2005, B00880660). A randomized, double-blind, controlled, parallel-group, 350-patient Phase II trial at 2 US centres to assess the synergistic effects of M-40403 in combination with morphine for moderate-to-severe pain following dental surgery is complete. Patients received morphine 0.04, 0.08 or 0.12mg/kg iv alone or in combination with M-40403 0.25mg/kg or M-40403 0.25mg/kg alone. M-40403 improved the overall analgesic profile of morphine, and made the dose-response profile more predictable, with faster onset, longer duration, greater peak effect and greater overall effect. Median time to onset of analgesia in the M-40403 + morphine 0.08mg/kg group was 22.5min, cf >480min for patients on morphine 0.08mg/kg alone, and median time to rescue medication for the M-40403 + morphine 0.12mg/kg group was 2.76hr cf 1.53hr for morphine 0.12mg/kg alone. Adding M-40403 to a low dose of morphine gave pain relief similar to the highest dose of morphine administered alone but without a concomitant increase in morphine side-effects (Press release, MetaPhore, 27 Apr 2004). In a randomized, double-blind, placebo-controlled Phase II study in patients with moderate-to-severe pain following first metatarsal bunionectomy, at 2 US sites, 3 different doses of M-40403 iv x30min + fixed dose morphine iv x10min demonstrated a good safety profile. A randomized, double-blind, placebo-controlled Phase II trial has been initiated in approximately 240 post-bunionectomy pain patients at 2 US sites to compare 0.25 and 0.0625mg/kg M-40403 alone and in combination with morphine (Press release, MetaPhore, 27 Apr 2004; BioVenture View Daily Online, 4 May 2005, B00880660). In a single-dose, randomized, double-blind, parallel-group Phase IIa trial, 250 patients with mild-to-severe pain after dental extraction received M-40403 5, 10 or 20mg iv or ketorolac 30mg (qv). Significant pain relief with 20mg was observed and was superior cf placebo for up to 1hr following molar extraction, with no serious adverse events (Press release, MetaPhore, 12 Jun 2003). Phase II trials in advanced skin and end-stage kidney cancers in combination with IL-2 were conducted (Company Web Page, MetaPhore, 8 Dec 2003). Phase II trials of M-40403 po to stop or reverse RA progression are expected in 2005 (JP Morgan 22nd Ann Healthcare Conf (San Francisco), 2004).
Phase I
It is in Phase I trials as a monotherapy for the treatment of neuropathic pain (Bio Venture Forum East (Atlanta), 2005). A Phase I trial to test safety, efficacy and pharmacokinetics in healthy volunteers was completed (Company Web Page, MetaPhore, 11 Jun 2002).
Preclinical
In rats, it inhibited fibrosis when coated on implanted biomedical devices (as M-40470) (Company Web Page, MetaPhore, 8 Dec 2003). In preclinical studies, it prevented or reversed the development of tolerance to morphine, and lowered the amount of morphine required for analgesia (Scrip Daily Online, 14 Jul 2003, S00808496). In a rat model of RA, M-40403 daily reduced inflammation by up to 56%, joint erosion by at least 70% and TNF-\a and IL-1b levels to those of non-arthritic rats (Press release, MetaPhore, 6 Dec 2001). In diabetic rats, M-40403 improved blood flow to nerves and restored normal relaxation of vessels around the sciatic nerve and normal motor nerve conduction velocity (Press release, MetaPhore, 28 Aug 2001). In 2 separate animal models, in combination with IL-2, M-40403 prevented the onset of IL-2-induced hypotension and enhanced IL-2's ability to kill malignant cells (Press release, MetaPhore, 22 Mar 2001). In rats, M-40403 administered 30min before or after inducing inflammation inhibited oedema and cytokine release associated with the inflammatory response. M-40403 was more efficacious than native SOD. Low-dose M-40403 also increased survival in a rat model of severe shock induced by reperfusion damage to the gut and intestine. At 4hr post-injury, survival of animals treated with M-40403 was 90% cf 0% of untreated animals (Press release, MetaPhore, 7 Oct 1999). In oral albumin-sensitized guinea pigs, M-40403 and M-40419 1mg/kg ip or by aerosol before or during antigen challenge dose-dependently attenuated the increase in severity of dyspnoea, decrease in latency of appearance of bronchospasm, increase in respiratory failure, mast cell degranulation and neutrophil infiltration. In rats, M-40401 and M-40403 10mg/kg ip reduced the histological and enzyme changes seen during zymosan-induced multiple organ failure (14th World Cong Pharmacol (San Francisco), 2002, Abs 134.34 & 137.36). In an animal colitis model, M-40403 reduced the extent and severity of inflammation and tissue damage of intestinal wall. It also reduced diarrhoea and body weight loss and elevated pro-inflammatory cytokines (TNF-\a and interleukin-1\B) (Press release, MetaPhore, 12 Dec 2001).
Licensing
MetaPhore plans to partner M-40403 before Phase IIb (Scrip Daily Online, 14 Jul 2003, S00808496). Updated by KS on 23/5/2005.
CX-516
新药名称：CX-516研发部门：Cortex Pharmaceuticals
作用简要机理：记忆增强药，适用于阿尔茨海默氏病认知功能症状、记忆力下降等神经系统疾病。本品通过增强AMPA受体的活性来改善AD的症状。在正常情况下，谷氨酸盐神经递质和AMPA受体结合，在学习和记忆过程中起重要作用。谷氨酸盐浓度低于正常水平会干扰学习和记忆，而谷氨酸盐浓度过高又会过度刺激细胞，引起细胞凋亡。阿尔茨海默氏病在不同的时间、不同环境下会出现谷氨酸盐过度和缺乏两种病理改变。CX-516可以通过增强AMPA的活性来补偿谷氨酸盐的不足。
研发阶段：目前在美国、欧盟进行II期临床研究 能不能给个结构式啊 新药名称: F647
研发部门: InterMune
作用简要机理: 一种新型广谱抗纤维化化合物,大量的研究已经证明本品是一种有效的细胞因子拮抗剂，能够通过参与调节某些因子，抑制成纤维细胞的生物学活性，导致细胞增殖受抑，基质胶原合成减少。作用的靶因子有以下几种 ：转化生长因子-β和结缔组织生长因子,肿瘤坏死因子-α(TNF-α)和其他炎症因子,血小板衍化生长因子,其它因子
研发阶段:进入II/III期临床研究阶段 1. AGI-1067 8 AGI-1067是选择性阻断动脉粥样硬化炎症过程的新型口服药物。AGI-1067阻断了血管内膜内皮细胞的信号传导，继而抑制了VCAM-1和其他炎症因子的生成。VCAM-1能使炎症细胞募集到内皮细胞表面，触发慢性炎症反应过程，最终导致动脉粥样硬化形成。AGI-1067 是具有抗氧化作用的降血脂药物普罗布考的单丁二酸酯。普罗布考Probucol能降低冠状血管成形术后的再狭窄，后因能引起心电图Q-T 间期延长等一系列不良反应，以及口服生物利用度的有限性和多变性而撤出美国市场。研究人员对普罗布考的结构进行修饰，开发出具有抗氧化作用和降低LDL 胆固醇水平双重作用机制的化合物AGI-1067。该化合物与普罗布考Probucol相比，水溶性和细胞穿透性更好，降脂作用和抗氧活性显著。此外，它还能抑制单细胞化学引诱剂蛋白-1（monocyte chemoattractant protein-1，MCP-1）和血管细胞粘附分子-1（vascular cell adhesion molecule-1，VCAM-1）的表达，美国AntheroGenics 公司目前正在进行Ⅲ期临床研究，考察其对患有冠状动脉疾病（CAD）的病人动脉粥样硬化的治疗情况。AGI-1067 是新血管保护剂家族中旨在降低血管壁炎症的首个药物。本品CAS：216167-82-7分子式：C35H52O5S2结构式：
[开发背景]：动脉粥样硬化是一种慢性炎症性疾病，而氧自由基的产生对动脉粥样硬化的发展有重要作用。普罗布考Probucol是一种已经上市的抗氧化剂，并具有降脂作用，当降脂作用的机制并不明了。Probucol可以降低血管成形术后血管再狭窄的发生率，但该产品已经被撤出美国市场，原因是该药物可以诱导QT间期延长、明显地降低HDL水平，以及有限的及不稳定的口服生物利用度，此外，该药物对内皮细胞VCAM-1的表达也缺乏影响。研究人员在对Probucol进行改进并寻找类似的化合物中发现了一种新的被称为复合血管保护剂的化合物（v-protectants）。这类化合物有双重作用，一方面可以保护血管内皮（通过抗氧化作用实现），另一方面可以降低血LDL-胆固醇的水平。AGI-1067是其中的一个化合物，该化合物是Probucol的单琥珀酸酯形式，比母体化合物具有更好的水溶性和细胞穿透性，具有明显的抗氧化活性和降脂活性。而且AGI-1067还可以抑制VCAM-1和MCP-1的表达（两者在粥样硬化损伤部位表达均上调）；抑制平滑肌细胞的增殖（该病理改变常见于动脉粥样硬化的后期）；在动脉粥样硬化和高脂血症动物模型中显示了疗效。AGI-1067被开发为冠心病患者的二级预防药物，所谓二级预防是指提高生存率、降低心血管事件再发率、降低干预治疗的需要以及提高生活质量。AGI-1067还可降低冠脉成形术后血管再狭窄的发生率。
阿斯利康公司已经与AtheroGenics公司（那斯达克上市公司名称代号是AGIX）达成许可协议，在全球开发和销售其抗炎心血管药物AGI-1067。
[AtheroGenics公司简介]：AtheroGenics公司致力于发现、开发和销售慢性炎症疾病治疗药物，包括心脏疾病（动脉粥样硬化）、类风湿性关节炎和哮喘。公司现在有4个药物处于临床阶段。公司现在正在组织进行代号为ARISE考察其主打药物AGI-1067作为口服药物治疗动脉粥样硬化的效果。第二个药物AGIX-4207是从公司专利protectant?技术平台衍生而来，是一种新型口服药物，处于治疗类风湿性关节炎的II期临床试验阶段。AGIX- 4207是静脉注射剂，已经完成了I期临床试验。AGI-1096是一个新型、口服药物，已经完成了预防器官移植排异反应的I期临床试验。
Gambogic Acid
At present , human hepatocellular carcinoma(HCC) is the most common liver cancer over the
world[1 ] and seeking HCC therapeutic agents with high
effect and low toxicity has become one of the main as2
signments for most pharmaceutical researchers.Gambogic Acid ( GA , C38 H44O8) is the
main active component of Gamboge. Early investigations
on Gamboge were mainly on its separation as well as
structural evaluation and crude extraction was used to
detect its anticancer activity in vitro and in vivo Re
cently , researchers of China Pharmaceutical University
applied a novel method to extract GA from Gamboge and
the contents of GA in the extract were no less than 95 %．Observations from our present studies in vivo have in
dicated that GA inhibited the tumor growth of H22 , S180 ,
EAC and EC on Kunming species mice , and Lewis lung
carcinoma in C57BL/ 6 mice. Results from our studies
in vitro also showed that GA had significant inhibitory
effect on human gastric carcinoma SGC27901 cells ,
MGC2803 cells , human lung carcinoma SPC2A1 cells
and BEL27402 cell . The objective of this study was
to determine whether the inhibitory activity of GA in hu2
man hepatoma SMMC27721 cells is correlated with
apoptosis and the possible mechanisms.
The effect of an anticancer drug was determined in
part by how readily the tumor cells undergo apoptosis
1 In this paper , the apoptosis induction of GA was
confirmed in human hepatoma SMMC27721 cell line and
the results also showed that apoptosis induced by GA
was mediated by p53 and Bax1 It was reported that the
tumor suppressor gene , p53 , functions as a cellular e2
mergency response system to induce cell growth arrest or
apoptosis． Our result of increase of p53 protein
may be a critical factor of apoptosis induction of GA1
Several pathways mediated p532induced apoptosis , and
one of these involved the Bax protein , which were the
p53 target and the proapoptotic member of the Bcl2
family of proteins． Bax could promote the cytosolic
release of cytochrome c , which in turn , activates cas2
pase 3 , one of the key executioners of apoptosis , and
then apoptosis occurred ． In addition , Bax could
bind with Bcl2and inhibit its function of apoptosis sup2
pressionSo the increase of p53 and Bax illustrated that
the mechanism of induction of apoptosis in SMMC27721
cells by GA involved activated p53 , Bax．
页:
[1]
