Orally Active, Brain Penetrant First-in-Class Small Molecule Midkine (MDK) Inhibitors for the Treatment of Malignancies and Non-Malignant Diseases
OwnerHareesh B. Nairinventor
Life of this patent
Estimating the term…
Abstract
An orally active, brain penetrant first-in-class small molecule midkine inhibitor for use in the treatment of triple-negative breast cancer, brain tumors (including glioblastoma, medulloblastoma, and NF1-mutant optic pathway gliomas), ovarian and endometrial cancers, lung cancer, as well as gynecologic non-malignant conditions such as endometriosis, uterine fibroids, and preterm birth, in which tumor cells and/or pathological cells exhibit heightened midkine signaling and express multiple midkine receptors.
Claims21
Orally available small molecule (HBS-101 and its analogues) compounds for the treatment of various types of cancers that inhibit midkine (MDK or MK) and blocks the interaction to its receptors PKCzeta, Syndycans, Notch2, ALK and LRP1 or integrins and blocks downstream targets such as STAT3 and NFkB.
Specifically, the following midkine antagonists below were claimed:
A midkine inhibitor for the treatment of malignancies and non-malignant diseases, said midkine inhibitor having the following structure:
- where R1=hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, long chain fatty acid with at least one hetero atom in the chain (n=1 to 18), said midkine inhibitor configured to inhibit midkine and block the interaction to midkine-binding receptors and configured to block downstream targets, and wherein said midkine inhibitor is orally active and brain penetrant.
A midkine inhibitory compound having the general structure of:
- where R1 is H, alkyl, cycloalkyl, alkenyl or a long chain fatty acid or any long chain with at least one hetero atom in the chain (n=1 to 18), and where R2 and R3 are F and R4 is H, alkyl hydroxy alkyl, methyl or ethyl ester, acid or amide.
The midkine inhibitory compound of claim 21, having the structures below:
Dependencies are inferred from the claim text.