Cytochroma Inc.

Bone Care International, Inc.

Queen's University at Kingston

Other

The Johns Hopkins University

The United States of America As Represented by the Secretary of

Glenville Jones

Jay A White

Charles W Bishop

Joyce C Knutson

Stephen Strugnell

Robert M Moriarty

P Martin Petkovich

Raju A Penmasta

Liang Guo

Lei Zhao

Ronald L Horst

Timothy A Reinhardt

Barbara R Beckett

Nicholas J Koszewski

Sanjay K Singhal

Gary H Posner

Martin Petkovich

Heather Ramshaw

Hong Woon Yang

Byung-Chul Suh

Kenneth R Crawford

Heung Bae Jeon

Qiang Wang

Mehmet Kahraman

Uttam Saha

Steven M Silverman

HeungBae Jeon

Mark Hatcher

Bethany Halford

Jae Kyoo Lee

The present invention provides novel D-ring and side-chain analogs of 1&#x3b1;,25-dihydroxyvitamin D, compositions comprising these compounds and methods of using these compounds as selective inhibitors of CYP24. In particular, the compounds of the invention are useful for treating diseases which benefit from a modulation of the levels of 1&#x3b1;,25-dihydroxyvitamin D, for example, cell-proliferative disorders.

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The present invention provides a novel all-trans-RA inducible all-trans-RA metabolizing cytochrome P450, P450RAI-2, that is predominantly expressed in the brain, cerebellum in particular. It is also expressed in normal and tumour lung tissue and in breast cancer cells and may have a correlation with lung and breast cancer. Human P450RAI-2 show 42% amino acid identity to human P450RAI-1 and when transfected into COS-1 cells causes the rapid conversion of all-trans-RA into more polar metabolites including the inactive products 4-oxo-RA, 4-OH-RA and 18-OH-RA. P450RAI-2, as with P450RAI-1, is also inducible in certain cultured cell lines exposed to all-trans-RA. Methods for and uses of the new polynucleotide, polypeptide, fragments thereof and inhibitors thereof, include the treatment of dermatological disorders, cancer and certain brain disorders.

P450RAI-2 (P450 cytochrome 26B), encoding nucleic acid molecules and methods and uses thereof

The present invention provides a novel all-trans-RA inducible all-trans-RA metabolizing cytochrome P450, P450RAI-2, that is predominantly expressed in the brain, cerebellum in particular. Human P450RAI-2 show 42% amino acid identity to human P450RAI-1 and when transfected into COS-1 cells causes the rapid conversion of all-trans-RA into more polar metabolites including the inactive products 4-oxo-RA, 4-OH-RA and 18-OH-RA. P450RAI-2, as with P450RAI-1, is also inducible in certain cultured cell lines exposed to all-trans-RA. Methods for and uses of the new polynucleotide, polypeptide, fragments thereof and inhibitors thereof, include the treatment of dermatological disorders and cancer.

Cytochrome P450RAI-2 and related proteins

Amino acid sequences and corresponding nucleic acid sequence of retinoid metabolizing protein found in human, mouse and zebrafish are described, as well as methods of using same.

Antibodies to retinoid metabolizing protein

Retinoid metabolizing protein

The present invention provides novel C24-sulfone analogs of 1&#x3b1;,25-dihydroxy vitamin D, compositions comprising these compounds and methods of using these compounds as selective inhibitors of CYP24. In particular, the compounds of the invention are useful for treating diseases which benefit from a modulation of the levels of 1&#x3b1;,25-dihydroxy vitamin D, for example, cell-proliferative disorders.

P450RAI-2(P450 Cytochrome 26B), encoding nucleic acid molecules and methods and uses thereof

The present invention provides novel 16-ene-C25-oxime and 16-ene-C-25-oxime ether analogs of 1&#x3b1;,25-dihydroxy vitamin D, compositions comprising these compounds and methods of using these compounds as inhibitors of CYP24. In particular, the compound of Formula I are useful for treating diseases which benefit from a modulation of the levels of 1&#x3b1;,25-dihydroxy vitamin D, for example, cell-proliferative disorders.

Low-calcemic oxime analogs of 1&#x3b1;,25-dihydroxy vitamin D3

1&agr;,24(S)-Dihydroxy vitamin D,which is useful as an active compound of pharmaceutical compositions for the treatment of disorders of calcium metabolism and for various skin disorders. The invention also includes preparation of synthetic 1&agr;,24(S)-dihydroxy vitamin D,starting from ergosterol which is converted in six steps to 24-hydroxyergosterol. 24-Hydroxyergosterol is irradiated and thermally converted to 24-hydroxy vitamin D,which is converted in six steps to 1&agr;,24(S)-dihydroxy vitamin D,. The syntheses also produced novel intermediates.

Methods for preparation and use of 1&agr;,24(S)-dihydroxy vitamin D2

Methods for preparation and use of 1&agr;,24 (S)-dihydroxy vitamin D2

1.alpha.,24(S)-Dihydroxy vitamin D.sub.2 which is useful as an active compound of pharmaceutical compositions for the treatment of disorders of calcium metabolism and for various skin disorders. The invention also includes preparation of synthetic 1.alpha.,24(S)-dihydroxy vitamin D.sub.2 starting from ergosterol which is converted in six steps to 24-hydroxyergosterol. 24-Hydroxyergosterol is irradiated and thermally converted to 24-hydroxy vitamin D.sub.2 which is converted in six steps to 1.alpha.,24(S)-dihydroxy vitamin D.sub.2. The syntheses also produced novel intermediates.

Methods for preparation and use of 1.alpha.,24(S)-Dihydroxy vitamin      .

Methods for preparation and use of 1.alpha., 24(S) -dihydroxy vitamin D2

Amino acid sequences and corresponding nucelic acid sequence of retinoid metabolizing protein found in zebrafish and human are described.

Growing community of inventors

Kingston, Canada

Glenville Jones