Institute of Medicinal Molecular Design Inc.

Shinjuku, Japan

Institute of Medicinal Molecular Design Inc.

Shinjuku, Japan
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Mizutani M.Y.,Institute of Medicinal Molecular Design Inc. | Takamatsu Y.,Institute of Medicinal Molecular Design Inc. | Ichinose T.,Institute of Medicinal Molecular Design Inc. | Itai A.,Institute of Medicinal Molecular Design Inc.
Chemical and Pharmaceutical Bulletin | Year: 2012

A fast method that can predict the binding affinities of chemicals to a target protein with a high degree of accuracy will be very useful in drug design and regulatory science. We have been developing a scoring function for affinity prediction, which can be applied to extensive protein systems, and also trying to generate a prediction scheme that specializes in each target protein, with as high a predictive power as possible. In this study, we have constructed a prediction scheme with target-specific scores for estimating ligand-binding affinities to human estrogen receptor α (ERα), considering the major conformational change between agonist- and antagonist-bound forms and the change in protonation states of histidine at the ligand-binding site. The generated scheme calibrated with fewer training compounds (23 for the agonist-bound form, 17 for the antagonist-bound form) demonstrated good predictive power (a predictive r 2 of 0.83 for 154 validation compounds); this was also true for compounds with frameworks that were quite different from those of the training compounds. Our prediction scheme will be useful in drug development targeting ERα and in primary screening of endocrine disruptors, and provides a successful method of affinity prediction considering the major conformational changes in a protein. © 2012 The Pharmaceutical Society of Japan.


Ohta K.,Tohoku Pharmaceutical University | Kawachi E.,Tokyo Medical and Dental University | Fukasawa H.,Institute of Medicinal Molecular Design Inc. | Shudo K.,Research Foundation Itsuu Laboratory | Kagechika H.,Tokyo Medical and Dental University
Bioorganic and Medicinal Chemistry | Year: 2011

Based upon the structure-activity relationships of diphenylamine derivatives with retinoid synergistic activity (RXR agonists), novel diphenylamine derivatives with a long alkyl chain (9a and 9b) or a benzyl group (10a-f) as the N-substituent were designed and synthesized. All the synthesized compounds dose-dependently inhibited HL-60 cell differentiation induced by 3.3 × 10 -10 M Am80. Among them, compound 10f showed the most potent inhibitory activity, and the mechanism was shown, by means of transactivation assay for RARs and RXRs, to involve antagonism against RARs. The N-substituent of the diphenylamine skeleton plays an important role in determining the receptor selectivity for RARs or RXRs, as well as the agonist or antagonist nature of the activity. © 2011 Elsevier Ltd. All rights reserved.


Suzuki J.-I.,Bunkyo University | Ogawa M.,Bunkyo University | Muto S.,Institute of Medicinal Molecular Design Inc. | Itai A.,Institute of Medicinal Molecular Design Inc. | And 3 more authors.
Expert Opinion on Investigational Drugs | Year: 2011

NF-κB is a key regulator of inflammation and immunity in cancer development. The IκB kinase (IKK) is a multisubunit complex containing catalytic subunits termed IKK-α, -β and -γ. It is well known that many pro-inflammatory stimuli require the IKK-β subunit for NF-κB activation. Areas covered: NF-κB affects the progression of inflammation-related diseases, such as myocardial ischemia, bronchial asthma, arthritis, cancer and other diseases. We review the characteristics and effects of these inhibitors on inflammatory and other diseases. Expert opinion: Various synthesized IKK inhibitors have been developed and they will be used clinically in the near future. © 2011 Informa UK, Ltd.


Patent
Institute of Medicinal Molecular Design. Inc. | Date: 2010-07-02

A medicament having inhibitory activity against NF-B activation, which comprises a compound represented by the following general formula (I) or pharmacologically acceptable salt as an active ingredient: wherein X represents a connecting group, A represents hydrogen atom or acetyl group, E represents an aryl group or a heteroaryl group, and ring X represents an arene or a heteroarene.


Patent
Shionogi & Co. and Institute Of Medicinal Molecular Design Inc. | Date: 2011-06-30

Disclosed is a compound which is useful as an 11-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula: its pharmaceutically acceptable salt, or a solvate thereof,


Patent
Institute of Medicinal Molecular Design Inc. | Date: 2011-01-12

The compound represented by the following formula (I) and the like have PAI-1 inhibition activity;wherein: R^(1) represents a C_(6-10) aryl group which may be substituted or the like; T represents a single bond or the like; m represents 0 or 1; when m is 0, G represents -N-C(=O)-CO_(2)H or the like; when m is 1, G represents an oxygen atom or the like; R^(2) represents a C_(6-10) aryl group which may be substituted or the like; E represents the following formula (II) wherein one of R^(31), R^(32), R^(33) and R^(34) represents the formula R^(1)-T-, each of the other three independently represents a hydrogen atom or the like, and R^(35) represents the formula -X-Y, a hydrogen atom or the like; X represents -CH_(2)- or the like; Y represents a carboxy group or the like; M represents a single bond or the like.


Patent
Institute Of Medicinal Molecular Design Inc. and Shionogi&Co. Ltd. | Date: 2010-07-21

Disclosed is a compound which is useful as an 11-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula:(i) when a broken line represents the presence of a bond, a wavy line represents the absence of a bond,R^(2) and R^(3) are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like,(ii) when a broken line represents the absence of a bond, a wavy line represents the presence of a bond,R^(1) and R^(4) are each independently hydrogen, halogen or the like,R^(2) and R^(3) are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, andR^(5) and R^(6) are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like.


Patent
Institute of Medicinal Molecular Design Inc. | Date: 2010-06-30

The compound represented by the following general formula (I) has an inhibitory activity on PAI-1 production;^(1) represents, for example, a hydrogen atom, or a 4-(morpholinyl)carlaonyl group, ring D represents, for example, a benzene ring or a benzene ring having substituent(s), and phenyl group E has substituent(s) such as a halogen atom, a halogenated alkyl group, an alkyl group, a halogenated alkoxy group, or an alkoxy group.


Patent
Institute Of Medicinal Molecular Design Inc. and Shionogi&Co. Ltd. | Date: 2010-01-06

Disclosed is a compound which is useful as an 11-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula:wherein R^(1) is optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycle or optionally substituted heterocyclealkyl,X is -O-, -NR^(3)-, -NR^(3) C(=O)- or -NR^(3) S(=O)_(2)-,R^(2) is optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl,R^(3) is hydrogen or optionally substituted alkyl.


Patent
Institute of Medicinal Molecular Design Inc. | Date: 2011-04-15

A method of generating a molecule-function network including bio-events by carrying out a connect search using a biomolecule-linkage database including information on the bio-events, and a method of predicting a pathway between an arbitrary biomolecule and an arbitrary bio-event in said network or a method of predicting the bio-events to which an arbitrary biomolecule in said network is related.

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