Physiologically active substance NK175203, process for productio

Details Physiologically active substance NK175203, process for productio Physiologically active substance NK175203, process for productio

1995-02-28

1996-04-09

Lilling, Herbert J.

Drug, bio-affecting and body treating compositions

Fermentate of unknown chemical structure

Having a known elemental analysis

435 702, 435 704, 435170, 4352535, 435886, C07G 1700, C12P 104, A61K 3574, C12N 120

Patent

active

055059449

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a novel physiologically active substance, NK175203, or a pharmaceutically acceptable salt thereof. More particularly, the present invention relates to a novel physiologically active substance NK175203 having an activity for promoting proliferation of bone marrow cells, or a salt thereof; a process for production thereof and pharmaceutical use thereof.


BACKGROUND ART

As bone marrow cell growth enhancers, there are known erythropoietin (Miyake, T. et al., J.B.C., 252, 5558, 1977) and G-CSF (Nicola, N. A., Annu. Rev. Biochem., 339, 27-30, 1989). However, these enhancers are protein preparations and thus unsuitable for frequent administrations. Therefore, it has been desired to find a low molecular weight compound having an activity comparable to these substances.


Disclosure of Invention

The present inventors have made various investigations on metabolites of microorganisms. As a result, it has been discovered that one strain belonging to the genus Streptomyces produces a physiologically active substance NK175203 having an activity of promoting proliferation of bone marrow cells.
That is, an object of the present invention is to provide a novel physiologically active substance, NK175203, having physico-chemical properties 1) through 10) described below, or a pharmaceutically acceptable salt thereof.


______________________________________ Calcd. (%) Found ______________________________________ C: 44.85 C: 44.82 H: 5.96 H: 5.87 N: 4.36 N: 4.34 ______________________________________ 1300, 1145, 1040 Hz), 2.97 (1H, dd, J=4.4, 13.6 Hz), 2.92-2.62 (5H, m), 2.50-2.10 (3H, m), 2.00 (3H, s), 1.81 (1H, m) 179.9 (s), 176.6 (s), 57.5 (d), 56.0 (d), 52.6 (d), 40.8 (t), 37.9 (t), 33.6 (t), 28.0 (t), 24.8 (q)
Another object of the present invention is to provide a process for producing the physiologically active substance NK175203 which comprises culturing a bacterium belonging to the genus Streptomyces and capable of producing the physiologically active substance NK175203 in a medium to produce and accumulate the physiologically active substance NK175203 in the culture broth, and collecting NK175203.
A further object of the present invention is to provide a pharmaceutical composition for promoting proliferation of bone marrow cells, comprising as an effective ingredient the physiologically active substance NK175203 or a pharmaceutically acceptable salt thereof.
A still further object of the present invention is to provide use of the physiologically active substance NK175203 or a pharmaceutically acceptable salt thereof as the effective ingredient of the pharmaceutical composition.
A still further object of the present invention is to provide bacteria belonging to the genus Streptomyces and capable of producing the physiologically active substance NK175203.


BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows UV spectrum (H.sub.2 O) of physiologically active substance NK175203.
FIG. 2 shows IR spectrum (KBr) of physiologically active substance NK175203.
FIG. 3 shows .sup.1 H-NMR (200 MHz, D.sub.2 O) of physiologically active substance NK175203.
FIG. 4 shows .sup.13 C-NMR (200 MHz, D.sub.2 O) of physiologically active substance NK175203.


BEST MODE FOR CARRYING OUT THE INVENTION

The physiologically active substance NK175203 which is the compound of the present invention may be a pharmaceutically acceptable salt thereof. Examples of such a salt include salts with alkali metals such as sodium, potassium, etc. and salts with alkaline earth metals such as calcium, and the like.
This novel physiologically active substance NK175203 is obtained by culturing a bacterium belonging to the genus Streptomyces and capable of producing the physiologically active substance NK175203 in a medium to produce and accumulate the physiologically active substance NK175203 in the culture broth, and collecting NK175203. A typical example of the bacteria producing the physiologically active substance NK175203 has the following bacteriological and physiological properties.
Observatio

REFERENCES:
patent: 4530835 (1985-07-01), Bunge et al.
patent: 4623622 (1986-11-01), Anderson
patent: 4703008 (1987-10-01), Lin
patent: 4822735 (1989-04-01), Anderson
patent: 4840934 (1989-06-01), Anderson
patent: 5162317 (1992-11-01), Hultner et al.
patent: 5169765 (1992-12-01), Borch et al.
patent: 5223605 (1993-06-01), Fanslow et al.

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