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
- Tamatinib
- DrugBank Accession Number
- DB07159
- Background
Not Available
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
Structure for Tamatinib (DB07159)
- Weight
- Average: 470.4536
Monoisotopic: 470.171396081 - Chemical Formula
- C22H23FN6O5
- Synonyms
- 6-({5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one
- External IDs
- R-406
- R406
- R406 free base
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 ATyrosine-protein kinase SYK inhibitorHumans AProto-oncogene tyrosine-protein kinase receptor Ret 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
- Not Available
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as methoxyanilines. These are organic compound containing an aniline group substituted at one or more positions by a methoxy group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Aniline and substituted anilines
- Direct Parent
- Methoxyanilines
- Alternative Parents
- Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Aminopyridines and derivatives / Aminopyrimidines and derivatives / Halopyrimidines / Imidolactams / Aryl fluorides / Heteroaromatic compounds show 11 more
- Substituents
- Alkyl aryl ether / Amine / Amino acid or derivatives / Aminopyridine / Aminopyrimidine / Anisole / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- RC3A285J2G
- CAS number
- 841290-80-0
- InChI Key
- NHHQJBCNYHBUSI-UHFFFAOYSA-N
- InChI
- InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)
- IUPAC Name
- 6-({5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}amino)-2,2-dimethyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one
- SMILES
- COC1=CC(NC2=NC=C(F)C(NC3=CC=C4OC(C)(C)C(=O)NC4=N3)=N2)=CC(OC)=C1OC
References
- General References
- Not Available
- External Links
- PubChem Compound
- 11213558
- PubChem Substance
- 99443630
- ChemSpider
- 9388620
- BindingDB
- 60665
- ChEBI
- 91348
- ChEMBL
- CHEMBL475251
- ZINC
- ZINC000006745792
- PDBe Ligand
- 585
- Wikipedia
- Fostamatinib
- PDB Entries
- 3piy
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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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 0.0291 mg/mL ALOGPS logP 3.84 ALOGPS logP 3.63 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 10.9 Chemaxon pKa (Strongest Basic) 2.77 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 128.75 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 122 m3·mol-1 Chemaxon Polarizability 45.81 Å3 Chemaxon Number of Rings 4 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 + 0.9941 Blood Brain Barrier - 0.5507 Caco-2 permeable - 0.5391 P-glycoprotein substrate Substrate 0.5394 P-glycoprotein inhibitor I Inhibitor 0.5475 P-glycoprotein inhibitor II Non-inhibitor 0.7339 Renal organic cation transporter Non-inhibitor 0.9449 CYP450 2C9 substrate Non-substrate 0.8517 CYP450 2D6 substrate Non-substrate 0.846 CYP450 3A4 substrate Substrate 0.6309 CYP450 1A2 substrate Non-inhibitor 0.5722 CYP450 2C9 inhibitor Non-inhibitor 0.6165 CYP450 2D6 inhibitor Non-inhibitor 0.9342 CYP450 2C19 inhibitor Non-inhibitor 0.6286 CYP450 3A4 inhibitor Non-inhibitor 0.6798 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5145 Ames test Non AMES toxic 0.6788 Carcinogenicity Non-carcinogens 0.8873 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.4303 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9942 hERG inhibition (predictor II) Non-inhibitor 0.7452
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 209.1852 predictedDeepCCS 1.0 (2019) [M-H]- 209.1852 predictedDeepCCS 1.0 (2019) [M+H]+ 211.57423 predictedDeepCCS 1.0 (2019) [M+H]+ 211.57423 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.0372 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.0372 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity)
- Specific Function
- Atp binding
- Gene Name
- SYK
- Uniprot ID
- P43405
- Uniprot Name
- Tyrosine-protein kinase SYK
- Molecular Weight
- 72065.76 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]
- Zheng TJ, Lofurno ER, Melrose AR, Lakshmanan HHS, Pang J, Phillips KG, Fallon ME, Kohs TCL, Ngo ATP, Shatzel JJ, Hinds MT, McCarty OJT, Aslan JE: Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function. Am J Physiol Cell Physiol. 2021 May 1;320(5):C902-C915. doi: 10.1152/ajpcell.00296.2020. Epub 2021 Mar 10. [Article]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698)
- Specific Function
- Atp binding
- Gene Name
- RET
- Uniprot ID
- P07949
- Uniprot Name
- Proto-oncogene tyrosine-protein kinase receptor Ret
- Molecular Weight
- 124317.465 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 September 15, 2010 21:19 / Updated at August 26, 2024 19:22