Targeted RNA degradation allows precision repurposing of protein-targeted small molecule medicines to RNA
View Patent ↗The protein targeted medicine, Dovitinib, has been repurposed to target a non-coding RNA by using selection and computational drug design via Inforna. Selectivity was achieved for pre-miR-21 by endowing the medicine with the ability to recruit RNA quality control enzymes to cleave the target.
1 . A method for targeting an RNA entity comprising contacting the RNA entity with a binding composition wherein
the RNA entity is (1) pre-miR-21, (2) an oncogenic cell line containing pre-miR-21, the cell line being a TNBC breast cancer cell line, MDA-MD-231 breast cancer cell line, prostate cancer cell line, or non-small-cell lung carcinoma cell line, (3) an animal host having an oncogenic cell line associated with pre-miR-21, (4) a human having an oncogenic malignancy associated with pre-miR-21, (5) an animal host having Alport Syndrome kidney disease, (6) a human having Alport Syndrome kidney disease or any disease in which pre-miR-21 is causative or contributive; and,
the binding composition comprises at least a Ribotac-Dovitinib having a formula of Compound 2 or a Protac-Dovitinib having a formula of Compound 3
2 . The method according to claim 1 wherein the contacting comprises contacting a TNBC breast cancer cell line, MDA-MD-231 breast cancer cell line, or anon-small-cell lung carcinoma cell line with the binding composition.
3 . The method according to claim 1 wherein the RNA entity is an animal host having Alport Syndrome kidney disease, wherein the animal host having Alport Syndrome kidney disease is an Alport Syndrome mouse model; or the RNA entity is a human having Alport Syndrome kidney disease.
4 . The method according to claim 1 wherein the contacting comprises contacting a TNBC breast cell cancer line with a binding composition comprising Compound 2 or Compound 3.
5 . The method according to claim 1 wherein the contacting comprises contacting an MDA-MB-231 breast cancer cell line with a binding composition comprising Compound 2 or Compound 3.
6 . The method according to claim 1 wherein the contacting comprising contacting a prostate cancer cell line with a binding composition comprising Compound 2 or Compound 3.
7 . The method according to claim 1 wherein the RNA entity is a breast cancer cell line or prostate cancer cell line present in an animal or human host.
8 . A composition comprising Compound 2 or Compound 3 or any combination thereof wherein
9 . The composition of claim 8 comprising Compound 2.
10 . The composition of claim 8 comprising Compound 3.
11 . A pharmaceutical composition comprising a composition of claim 8 and a pharmaceutically acceptable carrier.
12 . A method for treatment of breast cancer cells, prostate cancer cells, non-small cell lung cancer cells or Alport Syndrome kidney cells comprising contacting the cells with a pharmaceutical composition of claim 11 .
13 . The method according to claim 12 wherein the cancer cells are present in an animal host.
14 . The method according to claim 12 wherein the cancer cells are human cells and are present in a laboratory animal or human.
15 . The method according to claim 14 wherein the cancer cells are human cells and are present in a human.
16 . A method for determining a binding site on a pre-miRNA for Dovitinib comprising contacting the pre-miRNA with Compound 4 to form a complex, irradiating the complex, contacting the complex with a biotin azide to form a biotin-triazolyl-complex, and isolating the biotin-triazolyl complex with a streptavidin substance, wherein Compound 4 has the formula:
17 . The method of claim 1 , wherein the RNA entity is a human having a disease in which pre-miR-21 is causative or contributive.
18 . The method of claim 17 , wherein the disease is breast cancer, prostate cancer, or non-small cell lung cancer disease.
19 . The method of claim 12 , wherein the pharmaceutical composition comprises Compound 2.
20 . The method of claim 12 , wherein the pharmaceutical composition comprises Compound 3.
21 . The method of claim 1 , wherein the binding composition comprises Compound 2.
22 . The method of claim 1 , wherein the binding composition comprises Compound 3.