Wortmannin

Identification

Name
Wortmannin
Accession Number
DB08059
Type
Small Molecule
Groups
Experimental
Description

Wortmannin, a steroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii, is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks).

Structure
Thumb
Synonyms
  • Wartmannin
External IDs
NSC-627609 / SL-2052
Categories
UNII
XVA4O219QW
CAS number
19545-26-7
Weight
Average: 428.4319
Monoisotopic: 428.147117744
Chemical Formula
C23H24O8
InChI Key
QDLHCMPXEPAAMD-QAIWCSMKSA-N
InChI
InChI=1S/C23H24O8/c1-10(24)30-13-7-22(2)12(5-6-14(22)25)16-18(13)23(3)15(9-28-4)31-21(27)11-8-29-20(17(11)23)19(16)26/h8,12-13,15H,5-7,9H2,1-4H3/t12-,13+,15+,22-,23-/m0/s1
IUPAC Name
(1R,3R,5S,9R,18S)-18-(methoxymethyl)-1,5-dimethyl-6,11,16-trioxo-13,17-dioxapentacyclo[10.6.1.0^{2,10}.0^{5,9}.0^{15,19}]nonadeca-2(10),12(19),14-trien-3-yl acetate
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)C[C@@H](OC(C)=O)C1=C2C(=O)C2=C3C(=CO2)C(=O)O[C@H](COC)[C@]13C

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformNot AvailableHuman
USerine/threonine-protein kinase PLK1Not AvailableHuman
UPhosphatidylinositol 3-kinase regulatory subunit alphaNot AvailableHuman
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Wortmannin.
AlclometasoneThe risk or severity of adverse effects can be increased when Wortmannin is combined with Alclometasone.
AldesleukinThe risk or severity of adverse effects can be increased when Wortmannin is combined with Aldesleukin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Wortmannin.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Wortmannin.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Wortmannin.
AmcinonideThe risk or severity of adverse effects can be increased when Wortmannin is combined with Amcinonide.
AmikacinThe risk or severity of adverse effects can be increased when Amikacin is combined with Wortmannin.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Wortmannin.
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Wortmannin.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Compound
C15181
PubChem Compound
312145
PubChem Substance
99444530
ChemSpider
276037
BindingDB
15234
ChEBI
52289
ChEMBL
CHEMBL428496
HET
KWT
Wikipedia
Wortmannin
PDB Entries
1e7u / 3d5x / 3hhm

Clinical Trials

Clinical Trials
Not Available

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
PropertyValueSource
Water Solubility0.121 mg/mLALOGPS
logP2.31ALOGPS
logP1.44ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area109.11 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity106.86 m3·mol-1ChemAxon
Polarizability42.98 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9855
Blood Brain Barrier+0.957
Caco-2 permeable+0.5179
P-glycoprotein substrateSubstrate0.8161
P-glycoprotein inhibitor IInhibitor0.9581
P-glycoprotein inhibitor IIInhibitor0.9541
Renal organic cation transporterNon-inhibitor0.6551
CYP450 2C9 substrateNon-substrate0.8704
CYP450 2D6 substrateNon-substrate0.8509
CYP450 3A4 substrateSubstrate0.7654
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.5766
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7681
Ames testNon AMES toxic0.8847
CarcinogenicityNon-carcinogens0.9526
BiodegradationNot ready biodegradable0.9236
Rat acute toxicity4.0908 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8355
hERG inhibition (predictor II)Non-inhibitor0.6581
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oxasteroids and derivatives. These are steroid derivatives where a carbon atom of the steroid is replaced by an oxygen atom.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Oxasteroids and derivatives
Direct Parent
Oxasteroids and derivatives
Alternative Parents
Naphthopyrans / Naphthofurans / Naphthalenes / Furopyrans / Furoic acid esters / Aryl ketones / Pyrans / Dicarboxylic acids and derivatives / Heteroaromatic compounds / Lactones
show 5 more
Substituents
2-oxasteroid / Naphthopyran / Naphthofuran / Naphthalene / Furoic acid ester / Furopyran / Furoic acid or derivatives / Aryl ketone / Dicarboxylic acid or derivatives / Pyran
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cyclic ketone, organic heteropentacyclic compound, acetate ester, delta-lactone (CHEBI:52289)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific 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 recr...
Gene Name
PIK3CG
Uniprot ID
P48736
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Molecular Weight
126452.625 Da
References
  1. 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. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal o...
Gene Name
PLK1
Uniprot ID
P53350
Uniprot Name
Serine/threonine-protein kinase PLK1
Molecular Weight
68254.03 Da
References
  1. 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. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane receptor protein tyrosine kinase adaptor activity
Specific Function
Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for t...
Gene Name
PIK3R1
Uniprot ID
P27986
Uniprot Name
Phosphatidylinositol 3-kinase regulatory subunit alpha
Molecular Weight
83597.675 Da
References
  1. 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. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate...
Gene Name
PIK3CA
Uniprot ID
P42336
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Molecular Weight
124283.025 Da
References
  1. 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. [PubMed:10592235]

Drug created on September 15, 2010 15:28 / Updated on August 02, 2018 05:59