LY-294002
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Identification
- Generic Name
- LY-294002
- DrugBank Accession Number
- DB02656
- Background
Specific inhibitor of phosphatidylinositol 3-kinase.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 307.3432
Monoisotopic: 307.120843415 - Chemical Formula
- C19H17NO3
- Synonyms
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
- External IDs
- LY 294002
- LY-294002
- LY294002
- NSC-697286
- SF-1101
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform inhibitorHumans USerine/threonine-protein kinase pim-1 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
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key LY-294002 hydrochloride Not Available Not Available OQZQSRICUOWBLW-UHFFFAOYSA-N
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as chromones. These are compounds containing a benzopyran-4-one moiety.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzopyrans
- Sub Class
- 1-benzopyrans
- Direct Parent
- Chromones
- Alternative Parents
- Dialkylarylamines / Pyranones and derivatives / Morpholines / Benzene and substituted derivatives / Vinylogous amides / Heteroaromatic compounds / Oxacyclic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds show 2 more
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Chromone / Dialkyl ether / Dialkylarylamine / Ether / Heteroaromatic compound / Hydrocarbon derivative / Monocyclic benzene moiety show 12 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organochlorine compound, morpholines, chromones (CHEBI:65329)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 31M2U1DVID
- CAS number
- 154447-36-6
- InChI Key
- CZQHHVNHHHRRDU-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H17NO3/c21-17-13-18(20-9-11-22-12-10-20)23-19-15(7-4-8-16(17)19)14-5-2-1-3-6-14/h1-8,13H,9-12H2
- IUPAC Name
- 2-(morpholin-4-yl)-8-phenyl-4H-chromen-4-one
- SMILES
- O=C1C=C(OC2=C1C=CC=C2C1=CC=CC=C1)N1CCOCC1
References
- General References
- Not Available
- External Links
- KEGG Compound
- C15195
- PubChem Compound
- 3973
- PubChem Substance
- 46504762
- ChemSpider
- 3835
- BindingDB
- 12915
- ChEBI
- 65329
- ChEMBL
- CHEMBL98350
- ZINC
- ZINC000000006014
- PDBe Ligand
- LY2
- PDB Entries
- 1e7v / 1yi3 / 4azt / 4cfk / 6g0d
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 0.127 mg/mL ALOGPS logP 3.46 ALOGPS logP 3.41 Chemaxon logS -3.4 ALOGPS pKa (Strongest Basic) -2.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 38.77 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 98.5 m3·mol-1 Chemaxon Polarizability 32.75 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9943 Caco-2 permeable + 0.597 P-glycoprotein substrate Non-substrate 0.5198 P-glycoprotein inhibitor I Non-inhibitor 0.5554 P-glycoprotein inhibitor II Non-inhibitor 0.788 Renal organic cation transporter Non-inhibitor 0.5863 CYP450 2C9 substrate Non-substrate 0.852 CYP450 2D6 substrate Non-substrate 0.6473 CYP450 3A4 substrate Substrate 0.6371 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Inhibitor 0.6066 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.5061 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.527 Ames test AMES toxic 0.5727 Carcinogenicity Non-carcinogens 0.912 Biodegradation Not ready biodegradable 0.9166 Rat acute toxicity 2.3346 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7356 hERG inhibition (predictor II) Non-inhibitor 0.6569
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-0009000000-c1c581bb3dacffa14017 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0009000000-58aa896df848fe93869f Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0279000000-3a354125b03f1872bd4e Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0019000000-be2995f6dd9cfb279cdc Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0980000000-2a13b8b1d1455c9c1ad5 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0191000000-cfe092164767ad8f7f5a 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]- 182.5001165 predictedDarkChem Lite v0.1.0 [M-H]- 163.29152 predictedDeepCCS 1.0 (2019) [M+H]+ 182.4646165 predictedDarkChem Lite v0.1.0 [M+H]+ 165.68748 predictedDeepCCS 1.0 (2019) [M+Na]+ 182.4980165 predictedDarkChem Lite v0.1.0 [M+Na]+ 171.69722 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity)
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CG
- Uniprot ID
- P48736
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Molecular Weight
- 126452.625 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]
- 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]
2. DetailsSerine/threonine-protein kinase pim-1
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15528381, PubMed:1825810, PubMed:31548394). Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3) (PubMed:18593906). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (By similarity). The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (By similarity). Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (By similarity). Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis (PubMed:19749799). Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (PubMed:16356754). Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability (PubMed:12431783). Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (PubMed:18593906). Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (PubMed:18593906). May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (PubMed:10664448). Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (By similarity). Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394). Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (PubMed:37797010). Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (PubMed:18056989). Promotes brown adipocyte differentiation (By similarity)
- Specific Function
- ATP binding
- Gene Name
- PIM1
- Uniprot ID
- P11309
- Uniprot Name
- Serine/threonine-protein kinase pim-1
- Molecular Weight
- 35685.44 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 August 26, 2024 19:22