University of Miyazaki

Shionogi Company Limited

Other

Kenji Kangawa

Kazuo Kitamura

Motoo Yamasaki

Hisayuki Matsuo

Tanenao Eto

Shinya Ashizuka

Haruhiko Inatsu

Toshihiro Kita

Johji Kato

Keishi Kubo

Kenji Kuwasako

Shigeru Kubo

Kumiko Kumagaye

Sayaka Nagata

Yujiro Asada

The invention provides a novel adrenomedullin derivative sustainable for a long period which is capable of substantially suppressing unwanted side effects while maintaining pharmacological effects of adrenomedullin. In an exemplary embodiment, the invention relates to a compound represented by formula (I): A-CH—B (I) [wherein A is a modifying group comprising one or more polyethylene glycol groups, and B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, wherein the peptide moiety B is linked to the other moieties through a covalent bond of the nitrogen atom of the N-terminal α-amino group of the peptide moiety B to the carbon atom of the methylene group] or a salt thereof, or a hydrate thereof.

Long-acting adrenomedullin derivative

The invention provides a novel adrenomedullin derivative sustainable for a long period which is capable of substantially suppressing unwanted side effects while maintaining pharmacological effects of adrenomedullin. An aspect of the invention relates to a compound represented by formula (I): [wherein A is an Fc region of an immunoglobulin, B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, and L is a linking group comprising a peptide having any given amino acid sequence] or a salt thereof, or a hydrate thereof. Another aspect of the invention relates to a method for producing the compound represented by formula (I), and a medicament comprising the compound as an active ingredient.A-L-B&#x2003;&#x2003;(I).

Long-acting adrenomedullin derivative conjugated with Fc region of immunoglobulin

The invention provides a novel adrenomedullin derivative sustainable for a long period which is capable of substantially suppressing unwanted side effects while maintaining pharmacological effects of adrenomedullin. In an exemplary embodiment, the invention relates to a compound represented by formula (I): A-CH-B (I) [wherein A is a modifying group comprising one or more polyethylene glycol groups, and B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, wherein the peptide moiety B is linked to the other moieties through a covalent bond of the nitrogen atom of the N-terminal &#x3b1;-amino group of the peptide moiety B to the carbon atom of the methylene group] or a salt thereof, or a hydrate thereof.

There is provided a novel adrenomedullin derivative capable of sustainably acting for a longer period than natural adrenomedullin. The invention relates to a compound represented by formula (I): A-L-B (I), wherein A is a modifying group selected from the group consisting of a palmitoyl group and a polyethylene glycol group, L is a divalent linking group, n is an integer of 0 or 1, and B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, wherein the peptide moiety B is bound to the modifying group A or the linking group L via the N-terminal amino group of the peptide moiety B, or a salt thereof, or a hydrate thereof.

Long-acting adrenomedullin derivatives

The invention provides a novel adrenomedullin derivative sustainable for a long period which is capable of substantially suppressing unwanted side effects while maintaining pharmacological effects of adrenomedullin. In an exemplary embodiment, the invention relates to a compound represented by formula (I): A-CH&#x2014;B (I) [wherein A is a modifying group comprising one or more polyethylene glycol groups, and B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, wherein the peptide moiety B is linked to the other moieties through a covalent bond of the nitrogen atom of the N-terminal &#x3b1;-amino group of the peptide moiety B to the carbon atom of the methylene group] or a salt thereof, or a hydrate thereof.

An object of the present invention is to provide methods for preventing or treating a steroid-resistant or steroid-dependent inflammatory bowel disease. The object can be achieved by a method for preventing or treating a steroid-resistant or steroid-dependent inflammatory bowel disease in a patient in need of the prevention or treatment of the inflammatory bowel disease, comprises administering an effective amount of adrenomedullin, a modified product thereof having an activity of suppressing steroid-resistant or steroid-dependent inflammation, or a salt thereof having an activity of suppressing steroid-resistant or steroid-dependent inflammation, to the patient.

Method for prevention or treatment of intractable inflammatory bowel disease

Adrenomedullin which is a novel peptide having a hypotensive effect; proadrenomedullin N-terminal 20 peptide (proAM-N20) corresponding to an amino acid sequence of an N-terminus of proadrenomedullin, having a catecholamine secretion inhibitory effect; proadrenomedullin N-terminal 10-20 peptide (proAM-N(10-20)) having a Na channel inhibitory effect, and a gene encoding these peptides are provided. In addition, according to the present invention, these peptides in a sample containing adrenomdullin or proAM-N20 in an unknown amount can be quantified by using an antibody against adrenomedullin, proAM-N20, or its fragment.

Adrenomedullin

According to the present invention, adrenomedullin which is a novel peptide having a hypotensive effect; proadrenomedullin N-terminal 20 peptide (proAM-N20) corresponding to an amino acid sequence of an N-terminus of proadrenomedullin, having a catecholamine secretion inhibitory effect; proadrenomedullin N-terminal 10-20 peptide (proAM-N(10-20)) having a Na channel inhibitory effect, and a gene encoding these peptides are provided. In addition, according to the present invention, these peptides in a sample containing adrenomdullin or proAM-N20 in an unknown amount can be quantified by using an antibody against adrenomedullin, proAM-N20, or its fragment.

Antibodies to adrenomedullin

DNA encoding adrenomedullin

According to the present invention, adrenomedullin which is a novel peptide having a hypotensive effect; proadrenomedullin N-terminal 20 peptide (proAM-N20) corresponding to an amino acid sequence of an N-terminus of proadrenomedullin, having a catecholamine secretion inhibitory effect; proadrenomedullin N-terminal 10-20 peptide (proAM-N(10-20)) having a Na channel inhibitory effect, and a gene encoding these peptides are provided. In addition, according to the present invention, these peptides in a sample containing adrenomedullin or proAM-N20 in an unknown amount can be quantified by using an antibody against adrenomedullin, proAM-N20, or its fragment.

Growing community of inventors

Miyazaki, Japan

Kazuo Kitamura