# US 2022/0031701 A1 · Compositions and methods for treating diseases associated with uncontrolled inflammatory responses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2022/0031701 A1 - Document ID: US20220031701A1 - Status: Published application - Kind: A1 - Application number: 17/504,416 - Filed: 2021-10-18 - Published: 2022-02-03 - Earliest claimed: 2018-08-21 - Assignees: Synkrino Biotherapeutics, Inc. - Applicants: Synkrino Biotherapeutics, Inc. - Inventors: Jason Barbour; David Ott - Web page: https://patentgrep.com/patent/US20220031701A1 ## CPC - A61K 31/515: Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/497: containing further heterocyclic rings - A61K 31/50: Pyridazines; Hydrogenated pyridazines - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - C12Q 1/6883: for diseases caused by alterations of genetic material - G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation - G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - C12Q 2600/158: Expression markers - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY ## Abstract Methods of treating, controlling or managing diseases associated with uncontrolled inflammatory responses are provided. These methods comprise the administration of small molecule compounds that alter the activity of Tripartite motif containing 8 (TRIM8) in blood monocytes. Also provided are pharmaceutical compositions that comprise small molecule compounds that specifically target the E2-RING domain or the RING-RING dimerization domain of TRIM8 for the treatment, control or management of diseases associated with uncontrolled inflammatory responses. ## Claims ### Claim 1 A method of treating, controlling or managing a disease of cancer, the method comprising: altering TRIM8 activity in a subject's myeloid cells by administering to the subject a pharmaceutical composition, the pharmaceutical composition comprising a small molecule compound that targets a TRIM8 E2-RING binding site or a TRIM8 RING-RING dimerization binding site. ### Claim 2 (depends on 1) The method of claim 1, wherein the small molecule compound comprises the formula: ### Claim 3 (depends on 1) The method of claim 1, wherein the small molecule compound comprises the formula: (5E)-1-[(4-methoxyphenyl)methyl]-5-[(naphthalen-1-yl)methylidene]-1,3-diazinane-2,4,6-trione. ### Claim 4 (depends on 1) The method of claim 1, wherein the small molecule compound comprises the formula: ### Claim 5 (depends on 1) The method of claim 1, wherein the small molecule compound comprises the formula: 3-(2H-1,3-benzodioxol-4-yl)-3-(7-ethyl-1H-indol-3-yl)-1-[4-(4-nitrophenyl)piperazin-1-yl]propan-1-one. ### Claim 6 (depends on 1) The method of claim 1, wherein the myeloid cells are blood monocytes. ### Claim 7 (depends on 1) The method of claim 1, wherein the small molecule compound binds the RING-RING dimerization binding site of TRIM8, and wherein the small molecule compound comprises a region comprising a terminal 6-member ring linked to a 5-member ring linked via a flexible linker to a central 6-member aromatic ring motif, which in turn is linked to another terminal 6-member ring. ### Claim 8 (depends on 1) The method of claim 1, wherein the pharmaceutical composition is formulated for oral, enteral, parenteral, intravenous, pulmonary, mucosal, sub-mucosal or transdermal administration. ### Claim 9 (depends on 8) The method of claim 8, wherein the pharmaceutical composition contains one or more pharmaceutically acceptable excipients, diluents, adjuvants, stabilizers, emulsifiers, preservatives, colorants, buffers, flavor-imparting agents or pharmaceutically acceptable carriers suitable for oral, enteral, mucosal, sub-mucosal, parenteral, intravenous or transdermal administration. ### Claim 10 A pharmaceutical composition having a chemotherapeutic effect, the pharmaceutical composition comprising: a small molecule compound that binds TRIM8 E2-RING binding site or TRIM8 RING-RING dimerization binding site. ### Claim 11 (depends on 10) The pharmaceutical composition of claim 10, wherein the small molecule compound comprises the formula: ### Claim 12 (depends on 10) The pharmaceutical composition of claim 10, wherein the small molecule compound comprises the formula: (5E)-1-[(4-methoxyphenyl)methyl]-5-[(naphthalen-1-yl)methylidene]-1,3-diazinane-2,4,6-trione. ### Claim 13 (depends on 10) The pharmaceutical composition of claim 10, wherein the small molecule compound comprises the formula: ### Claim 14 (depends on 10) The pharmaceutical composition of claim 10, wherein the small molecule compound comprises the formula: 3-(2H-1,3-benzodioxol-4-yl)-3-(7-ethyl-1H-indol-3-yl)-1-[4-(4-nitrophenyl)piperazin-1-yl]propan-1-one. ### Claim 15 (depends on 10) The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is formulated in form of a capsule, tablet, pill, powder, granule, dragee, lozenge or bead for oral administration in immediate release, sustained release or controlled release form. ### Claim 16 (depends on 10) The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is formulated in form of liquid emulsions, solutions, suspensions, syrups or elixirs for oral administration. ### Claim 17 (depends on 10) The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is formulated in form of injectable depot for parenteral administration. ### Claim 18 (depends on 10) The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is formulated in form of patch or hydrogel for transdermal application.