Conjugated metabolites for cancer detection and treatment
AssigneeVanderbilt University
InventorEunyoung CHOI
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Abstract
Disclosed herein are compounds, research tools, and methods for detecting and treating epithelial cell dysplasia, precancer, and cancer in a cell or a subject. Also disclosed herein are compounds, research tools, and methods for inhibiting a dysplastic cell, inhibiting the transition of a metaplastic cell to a dysplastic cell, and reducing the incidence of carcinoma in a cell or a subject. In some embodiments, the compounds, research tools, and methods comprise an eicosenoic acid conjugate compound. In some embodiments, the compounds, research tools, and methods comprise a therapy comprising an SCD1 enzyme inhibitor.
Claims33
A compound of formula (I):
- wherein R1 is a fluorophore or a luminescent label selected from 7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (nitrobenzofurazan), nitrobenzoselenadiazole, fluorescein, rhodamine, aminomethylcoumarin acetate (AMCA), calcein, or cyanine.
A compound of formula (I):
- wherein R1 is selected from mertansine (DM1), taxol, calicheamicin, monomethyl auristatin E (MMAE), deruxtecan, SN-38, Pseudomonas exotoxin, diphtheria toxin, or Yttrium-90.
A research tool for detecting epithelial dysplasia, the research tool comprising a compound of formula (I):
- wherein R1 is a fluorophore or a luminescent label selected from 7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (nitrobenzofurazan), nitrobenzoselenadiazole, fluorescein, rhodamine, aminomethylcoumarin acetate (AMCA), calcein, or cyanine.
A research tool comprising a compound of formula (I):
- wherein R1 is selected from mertansine (DM1), taxol, calicheamicin, monomethyl auristatin E (MMAE), deruxtecan, SN-38, Pseudomonas exotoxin, diphtheria toxin, or Yttrium-90.
A method of inhibiting cancer or precancer in a cell or a subject in need thereof, the method comprising administering to the cell or the subject a therapeutically effective amount of a compound of formula (I):
- wherein R1 is selected from mertansine (DM1), taxol, calicheamicin, monomethyl auristatin E (MMAE), deruxtecan, SN-38, Pseudomonas exotoxin, diphtheria toxin, or Yttrium-90.
A method of treating a subject having cancer or precancer, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I):
- wherein R1 is selected from mertansine (DM1), taxol, calicheamicin, monomethyl auristatin E (MMAE), deruxtecan, SN-38, Pseudomonas exotoxin, diphtheria toxin, or Yttrium-90.
A method for inhibiting the transition of a metaplastic cell to a dysplastic cell, the method comprising administering a therapeutically effective amount of 4-(2-chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide (A939572) to a cell or a subject in need thereof.
A method for treating a metaplastic cell to reduce the incidence of carcinoma, the method comprising administering a therapeutically effective amount of 4-(2-chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide (A939572) to a cell or a subject in need thereof.
A method of making a compound comprising cis-11-eicosenoic acid conjugated to 7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (nitrobenzofurazan) or nitrobenzoselenadiazole:
- where X is O or Se;
- the method comprising:
- (a) combining cis-11-eicosenoic acid with dimethylformamide (DMF) solvent to create a solution;
- (b) adding N,N-diisopropylethylamine (DIPEA) to the solution;
- (c) adding 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) to the solution to create a reaction mixture;
- (d) mixing the reaction mixture;
- (e) adding nitrobenzofurazan or nitrobenzoselenadiazole to the reaction mixture to create a conjugate mixture;
- (f) mixing the conjugate mixture;
- and
- (g) one or more of diluting, washing, drying, or filtering the conjugate mixture to generate the compound.
A method of making a compound comprising cis-11-eicosenoic acid conjugated to mertansine:
- the method comprising:
- (a) combining mertansine carboxylic acid with dimethylformamide (DMF) solvent to create a solution;
- (b) adding hexafluorophosphate azabenzotriazole tetramethyl uranium (HATU) and N-methylmorpholine (NMM) to the solution to create a reaction mixture;
- (c) mixing the reaction mixture;
- (d) adding piperazine-conjugated cis-11-eicosenoic acid to the reaction mixture to create a conjugate mixture;
- (e) mixing the conjugate mixture;
- and
- (f) one or more of diluting, washing, drying, or filtering the conjugate mixture to generate the compound.
Dependencies are inferred from the claim text.