Pain Therapeutics, Inc.

Cassava Sciences, Inc.

Cassava Science, Inc.

Pain Therapeutic, Inc.

Lindsay Burns Barbier

Hoau-Yan Wang

Nan-Horng Lin

Andrei Blasko

Michael S Zamloot

Shawn Anthony Kucera

Jian Jim Wang

The preparation and properties of crystalline polymorphs and solvates of 1-benzyl-8-methyl-1,4,8-triazaspiro-[4.5]-decan-2-one free base and of the mono- and dihydrochloride salts and solvates thereof are disclosed, as is an amorphous polymorph of the dihydrochloride. A pharmaceutical composition containing one or more polymorphs and a method of using that composition are also disclosed.

Solid polymorphs of a FLNA-binding compound and its hydrochloride salts

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS.-

Method of inhibiting tau phosphorylation

An assay for Alzheimer's disease (AD) pathology in a living patient is disclosed wherein an amount of &#x3b1;7nAChR or TLR4 in a FLNA-captured protein complex or &#x3b1;7nAChR in an A&#x3b2;-captured protein complex or &#x3b1;7nAChR-FLNA, or TLR4-FLNA and/or &#x3b1;7nAChR-A&#x3b2;complex present as a protein-protein complex in a sample is compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is compared to an amount in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four pharmacophores of FIGS.-. An amount of protein or protein complex determined in the presence of medicament that is less than the first amount indicates a favorable treatment prognosis.

Alzheimer's disease assay in a living patient

A method of inhibiting the growth of cancer cells is disclosed in which cancer cells that contain an enhanced amount relative to non-cancerous cells of one or more of phosphorylated mTOR, Akt1, ERK2 and serine2152-phosphorylated filamin A are contacted with an FLNA-binding effective amount of a compound or a pharmaceutically acceptable salt thereof that binds to the pentapeptide of filamin A (FLNA) of SEQ ID NO: 1 and exhibits at least about 60 percent of the FITC-labeled naloxone binding amount when present at a 10 &#x3bc;M concentration and using unlabeled naloxone as the control inhibitor at the same concentration. A compound that binds to the FLNA pentapeptide preferably also contains at least four of the six pharmacophores of FIGS.-

Method for inhibiting growth of cancer cells

An assay for Alzheimer's disease (AD) pathology in a living patient is disclosed wherein an amount of &#x3b1;7nAChR or TLR4 in a FLNA-captured protein complex or &#x3b1;7nAChR in an A&#x3b2;-captured protein complex or &#x3b1;7nAChR-FLNA, TLR4-FLNA and/or &#x3b1;7nAChR-A&#x3b2;complex present as a protein-protein complex in a sample is compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is compared to an amount in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four pharmacophores of FIGS.-. An amount of protein or protein complex determined in the presence of the medicament that is less than the first amount indicates a favorable treatment prognosis.

An assay for Alzheimer's disease pathology (AD) in a living patient is disclosed wherein an amount of &#x3b1;7nAChR-FLNA, TLR4-FLNA and/or &#x3b1;7nAChR-A&#x3b2;complex present as a protein-protein complex in a sample is determined and compared to the amount in a standard sample from a person free of AD pathology. Use of one or more of those ratios provides an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein complex is determined and compared to an amount determined in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four of the six pharmacophores of FIGS.-. An amount of protein complex determined in the presence of the medicament less than the first determined amount indicates a favorable treatment prognosis.

A compound or its pharmaceutically acceptable salt, optionally including both individual enantiomeric forms, a racemate, diastereomers and mixtures thereof, composition and method are disclosed that can provide analgesia and reduce inflammation. A contemplated compound has a structure that corresponds to Formula A, wherein the R group substituents, d, e, f, k, n, m, D, E, F, K, G, P, Q, W, and Z are defined within. 

Filamin a binding anti-inflammatory and analgesic

A composition and method are disclosed that utilize an isolated polypeptide or analog thereof to inhibit the interaction of a mu-opioid receptor with filamin A. A contemplated polypeptide has an amino acid residue sequence illustrated by the formula: W-[XXX. . . XXX]ValAlaXGlyLeu[XXX. . . XXX]-Y, wherein the various elements are defined elsewhere. A contemplated method can be used to select a VAKGL-binding compound.

Analgesia with minimal tolerance and dependence by a mu opioid receptor agonist that also binds filamin A

A compound or its pharmaceutically acceptable salt, composition and method are disclosed that can provide analgesia and reduce inflammation. A contemplated compound has a structure that corresponds to Formula A, wherein the R group substituents, d, e, f, k, n, m, D, E, F, K, G, P, Q, W, and Z are defined within. 

Growing community of inventors

Austin, TX, United States of America

Lindsay Burns Barbier