4-((3r,4s,5r)-4-Amino-3,5-Dihydroxy-Hex-1-Ynyl)-5-Fluoro-3-[1-(3-Methoxy-1h-Pyrrol-2-Yl)-Meth-(Z)-Ylidene]-1,3-Dihydro-Indol-2-One
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- 4-((3r,4s,5r)-4-Amino-3,5-Dihydroxy-Hex-1-Ynyl)-5-Fluoro-3-[1-(3-Methoxy-1h-Pyrrol-2-Yl)-Meth-(Z)-Ylidene]-1,3-Dihydro-Indol-2-One
- DrugBank Accession Number
- DB03737
- Background
Not Available
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for 4-((3r,4s,5r)-4-Amino-3,5-Dihydroxy-Hex-1-Ynyl)-5-Fluoro-3-[1-(3-Methoxy-1h-Pyrrol-2-Yl)-Meth-(Z)-Ylidene]-1,3-Dihydro-Indol-2-One (DB03737)
- Weight
- Average: 385.3889
Monoisotopic: 385.143784348 - Chemical Formula
- C20H20FN3O4
- 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 UCyclin-dependent kinase 2 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 indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Indolines
- Direct Parent
- Indolines
- Alternative Parents
- Alkyl aryl ethers / Substituted pyrroles / Aryl fluorides / Benzenoids / Heteroaromatic compounds / Secondary carboxylic acid amides / Secondary alcohols / 1,2-aminoalcohols / Amino acids and derivatives / Lactams show 7 more
- Substituents
- 1,2-aminoalcohol / Alcohol / Alkyl aryl ether / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- RAKYKJWUUUKCCW-MPLBGYFPSA-N
- InChI
- InChI=1S/C20H20FN3O4/c1-10(25)19(22)16(26)6-3-11-13(21)4-5-14-18(11)12(20(27)24-14)9-15-17(28-2)7-8-23-15/h4-5,7-10,16,19,23,25-26H,22H2,1-2H3,(H,24,27)/b12-9-/t10-,16-,19+/m1/s1
- IUPAC Name
- (3Z)-4-[(3R,4S,5R)-4-amino-3,5-dihydroxyhex-1-yn-1-yl]-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one
- SMILES
- [H][C@](C)(O)[C@]([H])(N)[C@]([H])(O)C#CC1=C(F)C=CC2=C1\C(=C\C1=C(OC)C=CN1)C(=O)N2
References
- General References
- Not Available
- External Links
- PubChem Compound
- 5288222
- PubChem Substance
- 46505468
- ChemSpider
- 4450427
- BindingDB
- 10109
- ChEMBL
- CHEMBL354634
- ZINC
- ZINC000014947116
- PDBe Ligand
- FMD
- PDB Entries
- 1r78
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 0.0201 mg/mL ALOGPS logP 1.33 ALOGPS logP 1.01 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 11.32 Chemaxon pKa (Strongest Basic) 8.9 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 120.6 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 101.5 m3·mol-1 Chemaxon Polarizability 39.17 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 + 0.9137 Blood Brain Barrier - 0.6405 Caco-2 permeable - 0.5776 P-glycoprotein substrate Substrate 0.5 P-glycoprotein inhibitor I Non-inhibitor 0.9477 P-glycoprotein inhibitor II Non-inhibitor 0.978 Renal organic cation transporter Non-inhibitor 0.9538 CYP450 2C9 substrate Non-substrate 0.8925 CYP450 2D6 substrate Non-substrate 0.8303 CYP450 3A4 substrate Non-substrate 0.5114 CYP450 1A2 substrate Inhibitor 0.5943 CYP450 2C9 inhibitor Non-inhibitor 0.673 CYP450 2D6 inhibitor Non-inhibitor 0.8844 CYP450 2C19 inhibitor Non-inhibitor 0.7187 CYP450 3A4 inhibitor Non-inhibitor 0.785 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5649 Ames test Non AMES toxic 0.5576 Carcinogenicity Non-carcinogens 0.9047 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5951 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9906 hERG inhibition (predictor II) Non-inhibitor 0.7186
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014r-0009000000-a1242cae8d661d4e97df Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00yi-2019000000-31c3e75ceb6a5493431b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0gbi-1029000000-1e281155f181fc48442b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01b9-7019000000-ede1614f5f70262572e5 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014l-4191000000-43b5a45d5993ce0d5009 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00li-2194000000-501219def131ef216964 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]- 186.89459 predictedDeepCCS 1.0 (2019) [M+H]+ 189.0396 predictedDeepCCS 1.0 (2019) [M+Na]+ 194.95256 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-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involoved in regulation of telomere repar by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878)
- Specific Function
- Atp binding
- Gene Name
- CDK2
- Uniprot ID
- P24941
- Uniprot Name
- Cyclin-dependent kinase 2
- Molecular Weight
- 33929.215 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- 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 June 13, 2005 13:24 / Updated at June 12, 2020 16:52