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Chūō-ku, Japan

Noya M.,Jikei University School of Medicine | Tamez S.,Jikei University School of Medicine | Hijikuro I.,ChemGenesis Incorporated | Urashima M.,Jikei University School of Medicine
Tokyo Jikeikai Medical Journal | Year: 2012

1α,25-dihydroxyvitamin D3, which is the active form of vitamin D3, induces cancer cells to undergo apoptosis and differentiation and inhibits their growth. However, to date, no derivatives of active vitamin D3 have been used clinically as anticancer agents, because of the side effect of hypercalcemia. Accordingly, we experimentally searched for novel vitamin D3 derivatives that have anticancer effects but do not cause hypercalcemia. To search for anticancer effects, we examined 46 vitamin D3 derivatives, each with slight structural changes, during screening with HL60 human leukemia cells in vitro. The 50% inhibitory dose (ID50) is defined as the dose of an agent that inhibits tumor proliferation by 50% compared with a control solution. The ID50 for active vitamin D3 is 4 nM. The screening test determined that 20-epi-1α,25(OH)2D3 (VD01) and 20-epi-26,27-dihomo-1α,25(OH)2D3 (VD3), each with an ID50 of 0.07 nM, were the derivatives that most effectively inhibited the growth of tumors. We then created 20-ep¡-25(OH)D3 (VD47) and 20-epi-26,27-dihomo-25(OH)D3 (VD48), which were derivatives that lacked the 1α-hydroxyl group of VD01 and VD03, respectively, and performed a similar screening test in vitro. Only VD48 was found to have anticancer effects (ID50 2.5-1.25 nM); VD47 did not show anticancer effects (ID50 < 40 nM). Next, we compared the effects of VD03 and VD48 in C.B-17/Icr-scid/scidJcl mice into which HL60 human leukemia cells had been transplanted to verify whether these derivatives have anticancer effects without causing hypercalcemia. Because all the mice treated with VD03 died before the tumor proliferated, the anticancer effects could not be evaluated in these mice, although hypercalcemia was detected. On the other hand, hypercalcemia was not detected in mice treated with VD48, but anticancer effects were not detected either, because the extent of tumor proliferation was similar to that in the control group. In the present study, none of the vitamin D3 derivatives examined had anticancer effects without causing hypercalcemia. Source


Patent
Chemgenesis Incorporated | Date: 2014-02-28

The present invention relates to a liquid crystal compound that can be used as a base for injection formulations. The present invention provides an amphipathic compound having the following general formula (I): wherein X and Y each denotes a hydrogen atom or together denote an oxygen atom, n denotes an integer from 0 to 2, m denotes the integer 1 or 2, and R denotes a hydrophilic group generated by removal of one hydroxyl group from any one selected from the group consisting of glycerol, erythritol, pentaerythritol, diglycerol, triglycerol, xylose, sorbitol, ascorbic acid, glucose, galactose, mannose, dipentaerythritol, maltose, mannitol, and xylitol; as well as a base for injection formulations and depot formulation comprising the same.


Patent
Chemgenesis Incorporated | Date: 2010-12-27

The present invention relates to a liquid crystal compound that can be used as a base for injection formulations. The present invention provides an amphipathic compound having the following general formula (I): wherein X and Y each denotes a hydrogen atom or together denote an oxygen atom, n denotes an integer from 0 to 2, m denotes the integer 1 or 2, and R denotes a hydrophilic group generated by removal of one hydroxyl group from any one selected from the group consisting of glycerol, erythritol, pentaerythritol, diglycerol, triglycerol, xylose, sorbitol, ascorbic acid, glucose, galactose, mannose, dipentaerythritol, maltose, mannitol, and xylitol; as well as a base for injection formulations and depot formulation comprising the same.


Fuse S.,Tokyo Institute of Technology | Okada K.,Tokyo Institute of Technology | Iijima Y.,Tokyo Institute of Technology | Munakata A.,Japan Biological Informatics Consortium JBiC | And 5 more authors.
Organic and Biomolecular Chemistry | Year: 2011

The total synthesis of a natural product HDAC inhibitor, spiruchostatin B, was successfully achieved. A 5-step synthesis that included an asymmetric aldol reaction was carried out in an automated synthesizer to provide an (E)-(S)-3-hydroxy-7-thio-4-heptenoic acid segment that is the crucial structure of cysteine-containing, depsipeptidic natural products such as spiruchostatins, FK228, FR901375, and largazole for their inhibitory activity against HDACs. © 2011 The Royal Society of Chemistry. Source


Fuse S.,Tokyo Institute of Technology | Nakamura K.,Tokyo Institute of Technology | Mifune Y.,Tokyo Institute of Technology | Marubayashi H.,Tokyo Institute of Technology | And 4 more authors.
Synlett | Year: 2014

Linear and branched amphiphiles with different lengths of lipids and different numbers of hydroxyl groups were rapidly synthesized based on a dioxinone scaffold. The liquid crystalline (LC) properties of the synthesized amphiphiles in excess water were investigated by polarizing optical microscopy and small-angle X-ray scattering (SAXS) analysis. Novel β-keto ester based amphiphiles that formed non-lamellar, inverted LC phases were identified. © Georg Thieme Verlag Stuttgart · New York. Source

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