Aminopterin
(right click,save link as to download,it is a temp file,please download as soon as possible, you can also use CTRL+S to save the whole html page)
Basic Info
| Common Name | Aminopterin(F05492) |
| 2D Structure | |
| Description | Aminopterin Syndrome Sine Aminopterin (ASSA, OMIM 600325) is an embryopathy caused by maternal treatment with the olic acid antagonist aminopterin has been recognized since 1952 when aminopterin was used as an abortifacient. The characteristic phenotype of the children who survived infancy after having been exposed to aminopterin or its methyl derivative, methotrexate, in early pregnancy included a very unusual facies, skull anomalies, and skeletal defects.(OMIM). Aminopterin is an antimetabolite drug used in treatment of cancer and autoimmune diseases. It acts by inhibiting the metabolism of folic acid. - Wikipedia. The effects of the drug on intracellular metabolic processes, due to the inhibitory action on the enzyme dihydrofolate reductase, show that the result of this inhibition is more complex and is not limited to blockade of the reduction of folic acid alone. Although rescue methods are important in prevention of lethal effects of methotrexate, some metabolic pathways are insufficiently rescued, resulting in toxic reactions following methotrexate administration. (A7894) |
| FRCD ID | F05492 |
| CAS Number | 54-62-6 |
| PubChem CID | 2154 |
| Formula | C19H20N8O5 |
| IUPAC Name | 2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid |
| InChI Key | TVZGACDUOSZQKY-UHFFFAOYSA-N |
| InChI | InChI=1S/C19H20N8O5/c20-15-14-16(27-19(21)26-15)23-8-11(24-14)7-22-10-3-1-9(2-4-10)17(30)25-12(18(31)32)5-6-13(28)29/h1-4,8,12,22H,5-7H2,(H,25,30)(H,28,29)(H,31,32)(H4,20,21,23,26,27) |
| Canonical SMILES | C1=CC(=CC=C1C(=O)NC(CCC(=O)O)C(=O)O)NCC2=CN=C3C(=N2)C(=NC(=N3)N)N |
| Isomeric SMILES | C1=CC(=CC=C1C(=O)NC(CCC(=O)O)C(=O)O)NCC2=CN=C3C(=N2)C(=NC(=N3)N)N |
| Wikipedia | Aminopterin |
| Synonyms |
54-62-6
4-Amino-4-deoxypteroylglutamate
aminopterin
Aminopterinum
Aminopterine
Pteramina
4-Aminopteroyl-glutamic acid
4-Aminopteroylglutamic acid
4-Aminopteroyl-<R>glutamic acid
2-(4-((2,4-DIAMINOPTERIDIN-6-YL)METHYLAMINO)-BENZAMIDO)PENTANEDIOIC ACID
|
| Classifies |
Predicted: Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Pteridines and derivatives |
| Subclass | Pterins and derivatives |
| Intermediate Tree Nodes | Pteroic acids and derivatives - Folic acids and derivatives |
| Direct Parent | Folic acids |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Folic acid - Glutamic acid or derivatives - Hippuric acid or derivatives - Hippuric acid - N-acyl-alpha-amino acid - N-acyl-alpha amino acid or derivatives - Alpha-amino acid or derivatives - Aminobenzamide - Aminobenzoic acid or derivatives - Benzamide - Benzoic acid or derivatives - Benzoyl - Phenylalkylamine - Aniline or substituted anilines - Aminopyrimidine - Aralkylamine - Secondary aliphatic/aromatic amine - Pyrimidine - Pyrazine - Monocyclic benzene moiety - Benzenoid - Imidolactam - Dicarboxylic acid or derivatives - Heteroaromatic compound - Secondary carboxylic acid amide - Amino acid or derivatives - Amino acid - Carboxamide group - Secondary amine - Azacycle - Carboxylic acid derivative - Carboxylic acid - Hydrocarbon derivative - Amine - Organonitrogen compound - Organic oxide - Organic nitrogen compound - Organopnictogen compound - Carbonyl group - Primary amine - Organooxygen compound - Organic oxygen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as folic acids. These are heterocyclic compounds based on the 4-[(pteridin-6-ylmethyl)amino]benzoic acid skeleton conjugated with one or more L-glutamate units. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 440.42 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 9 |
| Complexity | 674 |
| Monoisotopic Mass | 440.156 |
| Exact Mass | 440.156 |
| XLogP | -2 |
| Formal Charge | 0 |
| Heavy Atom Count | 32 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.6168 |
| Human Intestinal Absorption | HIA+ | 0.8035 |
| Caco-2 Permeability | Caco2- | 0.7805 |
| P-glycoprotein Substrate | Substrate | 0.6625 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9325 |
| Non-inhibitor | 0.9910 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8940 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4952 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8749 |
| CYP450 2D6 Substrate | Non-substrate | 0.8116 |
| CYP450 3A4 Substrate | Non-substrate | 0.6336 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9188 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9199 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9330 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9382 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9707 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9719 |
| Non-inhibitor | 0.7778 | |
| AMES Toxicity | Non AMES toxic | 0.9016 |
| Carcinogens | Non-carcinogens | 0.9506 |
| Fish Toxicity | Low FHMT | 0.9667 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.5437 |
| Honey Bee Toxicity | Low HBT | 0.8527 |
| Biodegradation | Not ready biodegradable | 0.8542 |
| Acute Oral Toxicity | III | 0.5015 |
| Carcinogenicity (Three-class) | Non-required | 0.7032 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.0727 | LogS |
| Caco-2 Permeability | -0.7327 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.6501 | LD50, mol/kg |
| Fish Toxicity | 1.9479 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.2033 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| An ultra-sensitive monoclonal antibody-based competitive enzyme immunoassay for sterigmatocystin in cereal and oil products. | PLoS One | 2014 | 25184275 |
| Identification of a differentially expressed oligopeptide binding protein (OppA2) in Streptococcus uberis by representational difference analysis of cDNA. | J Bacteriol | 2003 Sep | 12923094 |
| Methotrexate use in rheumatoid arthritis. A Clinician's perspective. | Immunopharmacology | 2000 May | 10878293 |
Targets
- General Function:
- Serotonin receptor activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins.
- Gene Name:
- HTR5A
- Uniprot ID:
- P47898
- Molecular Weight:
- 40254.69 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
- Gene Name:
- OPRM1
- Uniprot ID:
- P35372
- Molecular Weight:
- 44778.855 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]