Method for induction of L-selectin shedding
US6498189B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Nov 18, 1999 |
| Grant date | Dec 24, 2002 |
| Priority date | — |
| Expiry date | Nov 18, 2019 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K31/285
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The invention provides anti-thiol reagents which inhibit enzyme activity of cell-associated protein disulfide isomerase (PDI) by oxidizing or blocking PDI active site vicinal thiol groups which normally participate in disulfide bond rearrangement of PDI substrates. Inhibition of this PDI function is particularly useful in blocking PDI-mediated entry of HIV or other virions into a host cell, as well as inhibiting lymphocyte traffic through the lymph nodes. The invention further provides an assay for the identification of such PDI inhibitors based on the discovery that inhibitors of the invention also induce shedding of the leucocyte L-selectin adhesion molecule. The invention additionally provides for suppression of inflammation and of lymph node entry by calmodulin antagonists that, like PDI inhibition, cause leukocyte L-selectin shedding.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.