This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Zunsemetinib
- DrugBank Accession Number
- DB16502
- Background
ATI-450 was under investigation in clinical trials (NCT05279417 and NCT05216224) for treating patients with rheumatoid arthritis and hidradenitis suppurativa, respectively. Additionally, ATI-450 was studied in a terminated trial (NCT05511519) to treat patients with psoriatic arthritis. Zunsemetinib is being investigated in a new clinical trial (NCT06374459) for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer with bone metastasis.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Zunsemetinib (DB16502)
- Weight
- Average: 513.93
Monoisotopic: 513.1379236 - Chemical Formula
- C25H22ClF2N5O3
- Synonyms
- (2′S)-3-Chloro-4-[(3,5-difluoro-2-pyridinyl)methoxy]-2′-[2-(1-hydroxy-1-methylethyl)-4-pyrimidinyl]-5′,6-dimethyl[1(2H),4′-bipyridin]-2-one
- (P)-3-chloro-4-((3,5-difluoropyridin-2-yl)methoxy)-2'-(2-(2-hydroxypropan-2-yl)pyrimidin-4yl)-5',6-dimethyl-2H-[1,4'-bipyridin]-2-one
- External IDs
- ATI 450
- ATI-450
- ATI450
- CDD 450
- CDD-450
- CDD450
Pharmacology
- Indication
Not Available
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
ATI-450 is an inhibitor of the MK2 pathway; it also has been observed to have anti-inflammatory activity. This compound likely targets and regulates pro-inflammatory cytokines which in turn will mitigate cytokine release syndrome. The drug is currently being investigated against rheumatoid arthritis, COVID-19, and cryopyrin-associated periodic syndrome (CAPS).
Target Actions Organism AMAP kinase-activated protein kinase 2 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- AX2VWG0ZCR
- CAS number
- 1640282-42-3
- InChI Key
- FQPQMJULRZINPV-UHFFFAOYSA-N
- InChI
- InChI=1S/C25H22ClF2N5O3/c1-13-10-30-18(17-5-6-29-24(32-17)25(3,4)35)9-20(13)33-14(2)7-21(22(26)23(33)34)36-12-19-16(28)8-15(27)11-31-19/h5-11,35H,12H2,1-4H3
- IUPAC Name
- SMILES
- CC1=CC(OCC2=NC=C(F)C=C2F)=C(Cl)C(=O)N1C1=C(C)C=NC(=C1)C1=NC(=NC=C1)C(C)(C)O
References
- General References
- External Links
- ChemSpider
- 58947940
- BindingDB
- 175242
- ChEMBL
- CHEMBL3704901
- ZINC
- ZINC000220110608
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide 2 Completed Treatment Hidradenitis Suppurativa (HS) 1 somestatus stop reason just information to hide 2 Completed Treatment Rheumatoid Arthritis 2 somestatus stop reason just information to hide 2 Terminated Treatment Cryopyrin-associated Periodic Syndromes (CAPS) 1 somestatus stop reason just information to hide 2 Terminated Treatment Psoriatic Arthritis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3
- Specific Function
- Atp binding
- Gene Name
- MAPKAPK2
- Uniprot ID
- P49137
- Uniprot Name
- MAP kinase-activated protein kinase 2
- Molecular Weight
- 45567.415 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at January 21, 2021 02:02 / Updated at August 27, 2024 19:16