3-(2-CHLOROPHENYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREA
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- 3-(2-CHLOROPHENYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREA
- DrugBank Accession Number
- DB08095
- Background
Not Available
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for 3-(2-CHLOROPHENYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREA (DB08095)
- Weight
- Average: 455.937
Monoisotopic: 455.17241743 - Chemical Formula
- C23H26ClN5O3
- Synonyms
- Not Available
Pharmacology
- Indication
Not Available
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
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
Target Actions Organism UMitogen-activated protein kinase 14 Not Available Humans - 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
- Not Available
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-phenylureas. These are compounds containing a N-phenylurea moiety, which is structurally characterized by a phenyl group linked to one nitrogen atom of a urea group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- N-phenylureas
- Direct Parent
- N-phenylureas
- Alternative Parents
- Methoxyanilines / Phenoxy compounds / Anisoles / Methoxybenzenes / Secondary alkylarylamines / Alkyl aryl ethers / Aminopyrimidines and derivatives / Chlorobenzenes / Imidolactams / Aryl chlorides show 9 more
- Substituents
- Alcohol / Alkyl aryl ether / Amine / Aminopyrimidine / Anisole / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Carbonic acid derivative show 26 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- ureas, aminopyrimidine, monochlorobenzenes, ethanolamines (CHEBI:47539)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- ZWYFTKPEHRQCCW-HNNXBMFYSA-N
- InChI
- InChI=1S/C23H26ClN5O3/c1-15(23(2,3)31)26-21-25-14-13-20(28-21)29(16-9-11-17(32-4)12-10-16)22(30)27-19-8-6-5-7-18(19)24/h5-15,31H,1-4H3,(H,27,30)(H,25,26,28)/t15-/m0/s1
- IUPAC Name
- 3-(2-chlorophenyl)-1-(2-{[(2S)-3-hydroxy-3-methylbutan-2-yl]amino}pyrimidin-4-yl)-1-(4-methoxyphenyl)urea
- SMILES
- [H][C@@](C)(NC1=NC=CC(=N1)N(C(=O)NC1=CC=CC=C1Cl)C1=CC=C(OC)C=C1)C(C)(C)O
References
- General References
- Not Available
- External Links
- PubChem Compound
- 6540299
- PubChem Substance
- 99444566
- ChemSpider
- 5022697
- BindingDB
- 50411056
- ChEMBL
- CHEMBL379760
- ZINC
- ZINC000016052060
- PDBe Ligand
- LIB
- PDB Entries
- 2ghl
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 data
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0184 mg/mL ALOGPS logP 3.78 ALOGPS logP 4.33 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 10.61 Chemaxon pKa (Strongest Basic) 2.55 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 99.61 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 127.1 m3·mol-1 Chemaxon Polarizability 46.38 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9705 Blood Brain Barrier - 0.6752 Caco-2 permeable - 0.5101 P-glycoprotein substrate Non-substrate 0.5222 P-glycoprotein inhibitor I Non-inhibitor 0.8706 P-glycoprotein inhibitor II Non-inhibitor 0.8797 Renal organic cation transporter Non-inhibitor 0.9128 CYP450 2C9 substrate Non-substrate 0.7153 CYP450 2D6 substrate Non-substrate 0.8171 CYP450 3A4 substrate Substrate 0.6003 CYP450 1A2 substrate Non-inhibitor 0.5172 CYP450 2C9 inhibitor Non-inhibitor 0.6858 CYP450 2D6 inhibitor Non-inhibitor 0.9081 CYP450 2C19 inhibitor Non-inhibitor 0.5085 CYP450 3A4 inhibitor Non-inhibitor 0.6456 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6183 Ames test Non AMES toxic 0.7586 Carcinogenicity Non-carcinogens 0.8141 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.2640 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.971 hERG inhibition (predictor II) Non-inhibitor 0.5767
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0003900000-a37629765aba257cb002 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0159-2091300000-cc7c494751527931eec5 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0gbi-0093100000-a53b1c5e0f8a72e189e4 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001l-9581000000-251433af1c55e240fb65 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-014l-0190000000-5f3af83dfb7253ce0970 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00gl-5985300000-bda2b58f087e072b32c9 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 194.97856 predictedDeepCCS 1.0 (2019) [M+H]+ 197.37413 predictedDeepCCS 1.0 (2019) [M+Na]+ 203.28667 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590)
- Specific Function
- ATP binding
- Gene Name
- MAPK14
- Uniprot ID
- Q16539
- Uniprot Name
- Mitogen-activated protein kinase 14
- Molecular Weight
- 41292.885 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Drug created at September 15, 2010 21:28 / Updated at June 12, 2020 16:52