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])/[[email protected]]([H])(OC)[[email protected]@]([H])(OC(O)=N)\C(C)=C([H])\[[email protected]]([H])(C)[[email protected]@]([H])(O)[[email protected]]([H])(C[[email protected]]([H])(C)CC2=C(OC)C(=O)C=C(N=C(O)\C(C)=C\1/[H])C2=O)OC

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UHeat shock protein HSP 90-alphaNot AvailableHuman
UHeat shock protein HSP 90-betaNot 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
DrugInteractionDrug group
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Geldanamycin.Approved, Investigational
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Geldanamycin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Geldanamycin.Experimental
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Geldanamycin.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Geldanamycin.Approved, Illicit, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Geldanamycin.Experimental, Investigational
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Geldanamycin.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Geldanamycin.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Geldanamycin.Approved
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Geldanamycin.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Geldanamycin.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Geldanamycin.Approved, Investigational
BoceprevirThe serum concentration of Geldanamycin can be decreased when it is combined with Boceprevir.Approved, Withdrawn
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Geldanamycin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Geldanamycin.Approved
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Geldanamycin.Approved
CarbamazepineThe metabolism of Geldanamycin can be increased when combined with Carbamazepine.Approved, Investigational
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Geldanamycin.Investigational, Withdrawn
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Geldanamycin.Approved, Investigational, Withdrawn
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Geldanamycin.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Geldanamycin.Approved, Vet Approved
Conjugated estrogensThe serum concentration of Conjugated estrogens can be decreased when it is combined with Geldanamycin.Approved
CyclobenzaprineThe serum concentration of Cyclobenzaprine can be increased when it is combined with Geldanamycin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Geldanamycin.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Geldanamycin.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Geldanamycin.Experimental
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Geldanamycin.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Geldanamycin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Geldanamycin.Approved
DibenzepinThe serum concentration of Dibenzepin can be increased when it is combined with Geldanamycin.Experimental
DienestrolThe serum concentration of Dienestrol can be decreased when it is combined with Geldanamycin.Approved, Investigational
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Geldanamycin.Approved, Investigational
DigitoxinDigitoxin may decrease the cardiotoxic activities of Geldanamycin.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Geldanamycin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Geldanamycin.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Geldanamycin.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Geldanamycin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Geldanamycin.Approved, Investigational
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Geldanamycin.Approved
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Geldanamycin.Approved
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Geldanamycin.Approved
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Geldanamycin.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Geldanamycin.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Geldanamycin.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Geldanamycin.Approved
EsmirtazapineThe serum concentration of Esmirtazapine can be increased when it is combined with Geldanamycin.Investigational
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Geldanamycin.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be decreased when it is combined with Geldanamycin.Approved
Estrogens, esterifiedThe serum concentration of Estrogens, esterified can be decreased when it is combined with Geldanamycin.Approved
Estrone sulfateThe serum concentration of Estrone sulfate can be decreased when it is combined with Geldanamycin.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Geldanamycin.Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Geldanamycin.Approved
GarlicThe serum concentration of Geldanamycin can be decreased when it is combined with Garlic.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Geldanamycin.Experimental
HexestrolThe serum concentration of Hexestrol can be decreased when it is combined with Geldanamycin.Withdrawn
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Geldanamycin.Approved
IprindoleThe serum concentration of Iprindole can be increased when it is combined with Geldanamycin.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Geldanamycin.Experimental
LofepramineThe serum concentration of Lofepramine can be increased when it is combined with Geldanamycin.Experimental
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Geldanamycin.Approved, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Geldanamycin.Approved
MethallenestrilThe serum concentration of Methallenestril can be decreased when it is combined with Geldanamycin.Experimental
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Geldanamycin.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Geldanamycin.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Geldanamycin.Approved, Illicit
MirtazapineThe serum concentration of Mirtazapine can be increased when it is combined with Geldanamycin.Approved
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Geldanamycin.Approved, Withdrawn
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Geldanamycin.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Geldanamycin.Experimental, Investigational
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Geldanamycin.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Geldanamycin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Geldanamycin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Geldanamycin.Experimental
PethidineThe risk or severity of adverse effects can be increased when Geldanamycin is combined with Pethidine.Approved
PimozideThe serum concentration of Pimozide can be increased when it is combined with Geldanamycin.Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Geldanamycin.Experimental
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Geldanamycin.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Geldanamycin.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Geldanamycin.Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Geldanamycin.Approved, Investigational
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Geldanamycin.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Geldanamycin.Approved
St. John's WortThe metabolism of Geldanamycin can be increased when combined with St. John's Wort.Investigational, Nutraceutical
Synthetic Conjugated Estrogens, AThe serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Geldanamycin.Approved
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Geldanamycin.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Geldanamycin is combined with Temsirolimus.Approved
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Geldanamycin.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Geldanamycin.Approved, Investigational
TipranavirThe serum concentration of Geldanamycin can be decreased when it is combined with Tipranavir.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Geldanamycin.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Geldanamycin.Approved
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Geldanamycin.Approved
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Geldanamycin.Approved, Investigational
VerapamilThe metabolism of Verapamil can be decreased when combined with Geldanamycin.Approved
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Geldanamycin.Approved
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
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
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
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 November 09, 2017 03:14