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Cardiovascular Diseases

Congenital Disorders

Nervous System Diseases

Small molecule drug

Enzyme

Disease domain score

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Targets

Most frequently developed targets

Disease Domain	Count

Hemic and Lymphatic Diseases	1
Immune System Diseases	1
Nervous System Diseases	1

Top 5 Drug Type	Count

Small molecule drug	2
Enzyme	1

Top 5 Target	Count

thrombin(Factor IIa)	1
uPA(Urokinase plasminogen activator)	1

3β-Hydroxysteroid-Δ24 reductase (DHCR24) is an endoplasmic reticulum-resident, multifunctional enzyme that possesses antiapoptotic and cholesterol-synthesizing activities. To clarify the molecular basis of the former activity, we investigated the effects of hydrogen peroxide (H2O2) on embryonic fibroblasts prepared from DHCR24-knockout mice (DHCR24−/− mouse embryonic fibroblasts). H2O2 exposure rapidly induced apoptosis, which was associated with sustained activation of apoptosis signal-regulating kinase-1 and stress-activated protein kinases, such as p38 MAPK and c-Jun N-terminal kinase. Complementation of the mouse embryonic fibroblasts by adenovirus expressing DHCR24 attenuated the H2O2-induced kinase activation and apoptosis. Concomitantly, intracellular generation of reactive oxygen species (ROS) in response to H2O2 was also diminished by the adenovirus, suggesting a ROS-scavenging activity of DHCR24. Such antiapoptotic effects of DHCR24 were duplicated in pheochromocytoma PC12 cells infected with adenovirus. In addition, it was found that DHCR24 exerted cytoprotective effects in the tunicamycin-induced endoplasmic reticulum stress by eliminating ROS. Finally, using in vitro-synthesized and purified proteins, DHCR24 and its C-terminal deletion mutant were found to exhibit high H2O2-scavenging activity, whereas the N-terminal deletion mutant lost such activity. These results demonstrate that DHCR24 can directly scavenge H2O2, thereby protecting cells from oxidative stress-induced apoptosis.

01 Jul 2008·Clinical and Applied Thrombosis/HemostasisQ4 · MEDICINE

Transition From Argatroban to Oral Anticoagulation With Phenprocoumon or Acenocoumarol: Effect on Coagulation Factor Testing

Q4 · MEDICINE

Article

Author: Harder, Sebastian ; Breddin, Hans-Klaus ; Osakabe, Masanori ; Drenth, Amanda F. ; Walenga, Jeanine M. ; Hoppensteadt, Debra A. ; Mayuga, Myttle ; Watanabe, Hikari ; Prechel, Margaret

Treatment with the thrombin inhibitor argatroban is often followed by vitamin K-antagonist treatment. In this study, the behavior of coagulation factors measured under these treatment regimens is shown. Healthy subjects received infusions of 1.0, 2.0, or 3.0 µg/kg/hr argatroban before and during phenprocoumon or acenocoumarol dosing. Quantitation of factors II, VII, IX, and X by clot-based assays resulted in dose dependent, approximately 20%, lower than expected values in the presence of argatroban. On the contrary, values for the inhibitors, protein C and protein S, were higher. Cotherapy exaggerated the effect by vitamin K-antagonist alone. However, testing by immunologic and chromogenic assays did not show any effect by argatroban. Coupled with a lack of bleeding in the subjects, these data suggests that argatroban does not affect coagulation proteins and that the observations are only an assay artifact. Assay interferences must be considered when measuring coagulation proteins in patients receiving thrombin inhibitors.

01 Feb 2008·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

5-Aryl-imidazolin-2-ones as a scaffold for potent antioxidant and memory-improving activity

Q4 · MEDICINE

Article

Author: Morinaka, Yasuhiro ; Ishibashi, Akira ; Tanaka, Masahiko ; Yuki, Satoshi ; Nishi, Hiroyoshi ; Hayashi, Yoshio ; Shinoda, Masaki ; Watanabe, Toshiaki ; Fukushima, Nobuko ; Watanabe, Kazutoshi

A series of 5-phenyl-substituted-N-alkyl-imidazolin-2-ones with potent radical-scavenging activity and lipid peroxidation inhibitory activity was synthesized. Many of the compounds showed memory-improving effect in animal models independent of the inhibitory activity on lipid peroxidation.

1

News (Medical) associated with Mitsubishi Pharma Corp.

15 May 2006

·www.biospace.com

Mitsubishi Pharma Corporation To Establish Pharmaceutical Development Company In Beijing, New Jobs

Tokyo, May 14, 2006 (JCN) - Mitsubishi Pharma announced on May 11 that it will set up a pharmaceutical development subsidiary in Beijing in October. To be capitalized at $1 million, Mitsubishi Pharma R&D (Beijing) (provisional name) will initially employ about 10 people.

100 Deals associated with Mitsubishi Pharma Corp.

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100 Translational Medicine associated with Mitsubishi Pharma Corp.

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Pipeline

Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

1

2

Approved

Other

55

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Nasaruplase ( uPA )	Myocardial Infarction More	Approved
Argatroban ( thrombin )	Arteriosclerosis Obliterans More	Approved
Y-320	Rheumatoid Arthritis More	Preclinical
QA-241	Bacterial Infections More	Discontinued
Y-20024 ( D2 receptor )	Psychotic Disorders More	Discontinued