Identification

Name
Geldanamycin
Accession Number
DB02424  (EXPT01571)
Type
Small Molecule
Groups
Experimental, Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
Categories
UNII
Z3K3VJ16KU
CAS number
30562-34-6
Weight
Average: 560.6359
Monoisotopic: 560.273380888
Chemical Formula
C29H40N2O9
InChI Key
QTQAWLPCGQOSGP-KSRBKZBZSA-N
InChI
InChI=1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
IUPAC Name
{[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-3,13-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-20,22-dioxo-2-azabicyclo[16.3.1]docosa-1(21),2,4,6,10,18-hexaen-9-yl]oxy}methanimidic acid
SMILES
[H]/C1=C([H])/[C@]([H])(OC)[C@@]([H])(OC(O)=N)\C(C)=C([H])\[C@]([H])(C)[C@@]([H])(O)[C@]([H])(C[C@]([H])(C)CC2=C(OC)C(=O)C=C(N=C(O)\C(C)=C\1/[H])C2=O)OC

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UHeat shock protein HSP 90-betaNot AvailableHuman
UHeat shock protein HSP 90-alphaNot AvailableHuman
UEndoplasmin
inhibitor
Human
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
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Geldanamycin.
PropacetamolThe serum concentration of Propacetamol can be increased when it is combined with Geldanamycin.
Food Interactions
Not Available

References

Synthesis Reference

Richard Hutchinson, "Recombinant polynucleotides encoding pro-geldanamycin producing polyketide synthase and accessory proteins, and uses thereof." U.S. Patent US20040077058, issued April 22, 2004.

US20040077058
General References
Not Available
External Links
KEGG Compound
C11222
PubChem Compound
5288382
PubChem Substance
46505674
ChemSpider
10272739
BindingDB
50008059
ChEBI
5292
ChEMBL
CHEMBL278315
Therapeutic Targets Database
DCL000325
PharmGKB
PA152031327
HET
GDM
Wikipedia
Geldanamycin
PDB Entries
1a4h / 1yet / 2esa / 2exl / 2weq / 2yga / 2yge / 2ygf / 3c11 / 4xdm

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentMalignancies, Hematologic1

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 Solubility0.00618 mg/mLALOGPS
logP2.39ALOGPS
logP3.76ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)7.24ChemAxon
pKa (Strongest Basic)4.54ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area167.96 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity164.41 m3·mol-1ChemAxon
Polarizability57.62 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9074
Blood Brain Barrier-0.8313
Caco-2 permeable-0.6156
P-glycoprotein substrateSubstrate0.5807
P-glycoprotein inhibitor IInhibitor0.8562
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterNon-inhibitor0.9493
CYP450 2C9 substrateNon-substrate0.8684
CYP450 2D6 substrateNon-substrate0.8444
CYP450 3A4 substrateSubstrate0.5922
CYP450 1A2 substrateNon-inhibitor0.8116
CYP450 2C9 inhibitorNon-inhibitor0.8498
CYP450 2D6 inhibitorNon-inhibitor0.8999
CYP450 2C19 inhibitorNon-inhibitor0.8016
CYP450 3A4 inhibitorNon-inhibitor0.9134
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9492
Ames testNon AMES toxic0.6172
CarcinogenicityNon-carcinogens0.9569
BiodegradationNot ready biodegradable0.7418
Rat acute toxicity2.3822 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9941
hERG inhibition (predictor II)Non-inhibitor0.9645
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 macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolactams
Sub Class
Not Available
Direct Parent
Macrolactams
Alternative Parents
Vinylogous esters / Vinylogous amides / Carbamate esters / Secondary carboxylic acid amides / Secondary alcohols / Organic carbonic acids and derivatives / Lactams / Cyclic ketones / Dialkyl ethers / Azacyclic compounds
show 4 more
Substituents
Macrolactam / Vinylogous ester / Vinylogous amide / Carbamic acid ester / Carboxamide group / Ketone / Lactam / Carbonic acid derivative / Secondary alcohol / Secondary carboxylic acid amide
show 16 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
lactam, macrocycle, benzoquinones (CHEBI:5292) / Ansamycins (C11222)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Utp binding
Specific Function
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Under...
Gene Name
HSP90AB1
Uniprot ID
P08238
Uniprot Name
Heat shock protein HSP 90-beta
Molecular Weight
83263.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
  3. 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
Tpr domain binding
Specific Function
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Under...
Gene Name
HSP90AA1
Uniprot ID
P07900
Uniprot Name
Heat shock protein HSP 90-alpha
Molecular Weight
84659.015 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virion binding
Specific Function
Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in...
Gene Name
HSP90B1
Uniprot ID
P14625
Uniprot Name
Endoplasmin
Molecular Weight
92468.06 Da
References
  1. Grenert JP, Sullivan WP, Fadden P, Haystead TA, Clark J, Mimnaugh E, Krutzsch H, Ochel HJ, Schulte TW, Sausville E, Neckers LM, Toft DO: The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem. 1997 Sep 19;272(38):23843-50. [PubMed:9295332]
  2. Carreras CW, Schirmer A, Zhong Z, Santi DV: Filter binding assay for the geldanamycin-heat shock protein 90 interaction. Anal Biochem. 2003 Jun 1;317(1):40-6. [PubMed:12729599]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 13:19