SEOCALCITOL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H46O3
Molecular Weight	454.6844
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3\C[C@@H](O)C[C@H](O)C3=C)[C@H](C)\C=C\C=C\C(O)(CC)CC

InChI

InChIKey=LVLLALCJVJNGQQ-SEODYNFXSA-N

InChI=1S/C30H46O3/c1-6-30(33,7-2)18-9-8-11-21(3)26-15-16-27-23(12-10-17-29(26,27)5)13-14-24-19-25(31)20-28(32)22(24)4/h8-9,11,13-14,18,21,25-28,31-33H,4,6-7,10,12,15-17,19-20H2,1-3,5H3/b11-8+,18-9+,23-13+,24-14-/t21-,25-,26-,27+,28+,29-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11875725
Curator's Comment: description was created based on several sources, including https://books.google.ru/books?id=p9VRjKlCXmcC&pg=PA71&lpg=PA71&dq=seocalcitol+discontinued&source=bl&ots=8CIlJR1gJm&sig=wj6rotcTmghtfbonv8nhNOKzKeo&hl=ru&sa=X&ved=0ahUKEwjOzvL4wujSAhXJjiwKHYoODxYQ6AEIKzAC#v=onepage&q=seocalcitol%20discontinued&f=false

Seocalcitol (EB 1089) is a vitamin D analog, and agonist of the vitamin D receptor. Antineoplastic activity of seocalcitol was tested in clinical trials against hepatocellular carcinoma, pancreatic, breast and colorectal cancer. Due to inconsistent results of clinical trials, development of seocalcitol was discontinued by Leo Pharma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9831485	Agonist 2678		0.02 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Hepatocellular carcinoma 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12865912	Primary	Phase III 656	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11875725	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9662243	Primary	Phase I 428	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9662243	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
146 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11037113	2.4 μg/kg 1 times / day multiple, oral dose: 2.4 μg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		SEOCALCITOL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
738 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11037113	2.4 μg/kg 1 times / day multiple, oral dose: 2.4 μg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		SEOCALCITOL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11037113	2.4 μg/kg 1 times / day multiple, oral dose: 2.4 μg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		SEOCALCITOL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009CVE	https://www.1pchem.com/search?query=1P009CVE
AK Scientific	4036AH	https://aksci.com/item_detail.php?cat=4036AH
AlchemyPharm	AP00502	https://www.alchemypharm.com/pharm/search.do?q=AP00502
AstaTech	41539	http://astatechinc.com/CPSResult.php?CRNO=41539
BLD Pharm	BD151041	http://www.bldpharm.com/search/Search.html?keyword=BD151041
BOC Sciences	134404-52-7	http://www.bocsci.com/description.asp?cas=134404-52-7
Cayman Chemical	21579	http://www.caymanchem.com/app/template/Product.vm/catalog/21579
MedChem Express	HY-32341	https://www.medchemexpress.com/search.html?q=HY-32341&ft=&fa=&fp=
MolPort	MolPort-023-277-025	https://www.molport.com/shop/molecule-link/MolPort-023-277-025
Tocris	3993	https://www.tocris.com/search.php?Type=QuickSearch&Value=3993
eMolecules	45475475	https://orderbb.emolecules.com/search/#?query=45475475
mcule	MCULE-1400666187	https://mcule.com/MCULE-1400666187/

PubMed

Title	Date	PubMed
Studies on two new vitamin D analogs, EB 1089 and KH 1060: effects on bone resorption and osteoclast recruitment in vitro.	1995 Oct	8573413
Cytotoxic effects of 1 alpha,25-dihydroxyvitamin D3 and synthetic vitamin D3 analogues on a glioma cell line.	1996 Feb 27	8620449
Apoptotic regression of MCF-7 xenografts in nude mice treated with the vitamin D3 analog, EB1089.	1998 Apr	9528999
A phase I study of the vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer.	1998 Jul	9662243
Inhibition of endothelial cell activation by nitric oxide donors.	2000 Nov	11046123
The vitamin D3 analog EB1089 induces apoptosis via a p53-independent mechanism involving p38 MAP kinase activation and suppression of ERK activity in B-cell chronic lymphocytic leukemia cells in vitro.	2003 Apr 1	12446453
Inhibition of MG-63 cell cycle progression by synthetic vitamin D3 analogs mediated by p27, Cdk2, cyclin E, and the retinoblastoma protein.	2003 Aug 1	12907249
Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.	2005 Jul	15985530
Prostate cancer cell type-specific involvement of the VDR and RXR in regulation of the human PTHrP gene via a negative VDRE.	2006 Feb	16243370
Investigation of the mechanisms by which EB1089 abrogates apoptosis induced by 9-cis retinoic acid in pancreatic cancer cells.	2006 Jan	16340750
Prostate-derived Ets transcription factor as a favorable prognostic marker in ovarian cancer patients.	2008 Sep 15	18567002

Patents

Sample Use Guides

In Vivo Use Guide

In a phase II clinical study against hepatocellular carcinoma, Seocalcitol was administered orally at starting doses 10 ug/day.

Route of Administration: Oral

In Vitro Use Guide

U937 cells were seeded at 1 × 105 cells/ml in culture flasks at 5ml cells/flask. EB 1089 was added in the concentrations 10-9 - 10-12 M; control cultures received the diluent, 2-propanol. After 96 h, proliferation was assessed by counting of cells, and IC50 was calculated from the dose-response curves.

Name

Type

Language

SEOCALCITOL

Official Name

English

seocalcitol [INN]

Common Name

English

CB-1089

Code

English

SEOCALCITOL [MI]

Common Name

English

SEOCALCITOL [MART.]

Common Name

English

Seocalcitol [WHO-DD]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/01/052