In vitro compositions comprising human sample and amyloid targeting agent
AssigneeAmydis Diagnostics, Inc.
InventorStella Sarraf
Life of this patent
Estimating the term…
Abstract
Provided herein are compositions and methods useful for detection of amyloid related disorders in samples, such as human tissue, cell or body fluid. Use of the compositions and methods herein allows for the rapid, in vitro detection of amyloid accumulation, often before amyloid disorder symptoms are manifest or without introduction of foreign fluorophore molecules into a subject.
Claims153
A composition comprising a) a human sample selected from the list of human samples consisting of a tissue, a cell population, a cell, a fluid, and an extract and b) a compound of Formula I, or a pharmaceutically acceptable salt thereof:
- wherein
- EDG is an electron donating group;
- each Ar is independently C1-C14 arylene or C1-C14 heteroarylene, each optionally substituted with one more R1;
- each R1 is independently halogen, —OR2, —NR3R4, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 cycloalkyl, C1-C10 heterocycloalkyl, C1-C10 arylene, or C1-C10 heteroarylene wherein the alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, arylene, or heteroarylene is optionally substituted with one or more R5;
- R2, R3 and R4 are independently hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 cycloalkyl, C1-C10 heterocycloalkyl, arylene, or C1-C10 heteroarylene, each of which except for hydrogen is optionally substituted with one or more R5;
- each R5 is independently halogen, —OR6, —NR7R8, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 cycloalkyl, C1-C10 heterocycloalkyl, C1-C10 arylene, or C1-C10 heteroarylene;
- R6, R7, R8 and R84 are independently hydrogen or C1-C10 alkyl;
- EWG is an electron withdrawing group;
- WSG is a water soluble group;
- X is C═O or SO2;
- Y is NH, or S;
- each w is independently an integer from 1-5;
- each x is independently an integer from 0-10;
- each y is independently an integer from 0-10;
- and
- z is an integer from 1-10.
A composition comprising a) a human sample selected from the list of human samples consisting of a tissue, a cell population, a cell, a fluid, and an extract and b) a compound of Formula II, or a pharmaceutically acceptable salt thereof:
- wherein
- EDG is an electron donating group;
- Ar2 and each Ar1 is independently C1-C14 arylene or C1-C14 heteroarylene, each optionally substituted with one more R41;
- each R41 is independently halogen, —OR42, —CN, —NR43R44, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 cycloalkyl, C1-C10 heterocycloalkyl, C1-C10 arylene, or C1-C10 heteroarylene wherein the alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, arylene, or heteroarylene is optionally substituted with one or more R45;
- R42, R43 and R44 are independently hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 cycloalkyl, C1-C10 heterocycloalkyl, C1-C10 arylene, or C1-C10 heteroarylene, each of which except for hydrogen is optionally substituted with one or more R45;
- each R45 is independently halogen, —OR46, —NR47R48, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 cycloalkyl, C1-C10 heterocycloalkyl, C1-C10 arylene, or C1-C10 heteroarylene;
- R46, R47 and R48 are independently hydrogen or C1-C10 alkyl;
- EWG is an electron withdrawing group;
- Y is absent, O, NH, or S;
- WSG is hydrogen or a water soluble group;
- x is an integer from 0-10;
- y is an integer from 0-10;
- and
- z is an integer from 1-10.
A method of detecting an amyloid disorder in a human subject comprising the steps of:
- contacting a sample from the human subject to a molecule having a first spectal profile when unbound and a second spectal profile when bound to a protein aggregate;
- determining a spectal profile for the sample contacted to the molecule;
- wherein the second spectal profile indicates presence of the amyloid disorder;
- and
- wherein the method has a sensitivity of at least 80% and a specificity of at least 80%.
Dependencies are inferred from the claim text.