Details of the Drug

General Information of Drug (ID: DMJS4RP)

Drug Name
PMID26882240-Compound-32
Affected Organisms
Humans and other mammals
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 616.7
Logarithm of the Partition Coefficient (xlogp) 2
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
Elimination
10.6C14.8% of delivered dose is excreted in urine in unchanged form (in a mice study) [1]
Half-life
The concentration or amount of drug in body reduced by one-half in 9.9 - 54.1 hours [2]
Metabolism
The drug is metabolized via purified human cytochrome P450 reductase (CYP3A4/3A5) to quinones and hydroquinones [3]
Vd
The volume of distribution (Vd) of drug is 385 L []
Chemical Identifiers
Formula
C32H48N4O8
IUPAC Name
[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
Canonical SMILES
C[C@H]1C[C@@H]([C@@H]([C@H](/C=C(/[C@@H]([C@H](/C=C\\C=C(\\C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)/C)OC)OC(=O)N)\\C)C)O)OC
InChI
InChI=1S/C32H48N4O8/c1-18-14-22-27(34-12-13-36(5)6)24(37)17-23(29(22)39)35-31(40)19(2)10-9-11-25(42-7)30(44-32(33)41)21(4)16-20(3)28(38)26(15-18)43-8/h9-11,16-18,20,25-26,28,30,34,38H,12-15H2,1-8H3,(H2,33,41)(H,35,40)/b11-9-,19-10+,21-16+/t18-,20+,25+,26+,28-,30+/m1/s1
InChIKey
KUFRQPKVAWMTJO-LMZWQJSESA-N
Cross-matching ID
PubChem CID
5288674
ChEBI ID
CHEMBL65324
CAS Number
467214-20-6
UNII
001L2FE0M3
DrugBank ID
DB12442
TTD ID
D03OYJ
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Hypoxia-inducible factor 1 (HIF-1) TTUX68I NOUNIPROTAC Inhibitor [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [6]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Gene/Protein Processing [6]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Gene/Protein Processing [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [5]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [5]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [6]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Gene/Protein Processing [6]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Gene/Protein Processing [5]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Gene/Protein Processing [8]
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References

1 Hu ZY, Lu J, Zhao Y: A physiologically based pharmacokinetic model of alvespimycin in mice and extrapolation to rats and humans. Br J Pharmacol. 2014 Jun;171(11):2778-89. doi: 10.1111/bph.12609.
2 Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies. Eur J Cancer. 2010 Jan;46(2):340-7. doi: 10.1016/j.ejca.2009.10.026. Epub 2009 Nov 27.
3 Shill HA, Stacy M: Update on ropinirole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:33-6. Epub 2009 Apr 8.
4 Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015).Expert Opin Ther Pat. 2016;26(3):309-22.
5 FGFR3 translocations in bladder cancer: differential sensitivity to HSP90 inhibition based on drug metabolism. Mol Cancer Res. 2014 Jul;12(7):1042-54. doi: 10.1158/1541-7786.MCR-14-0004. Epub 2014 Apr 30.
6 Co-treatment with heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and vorinostat: a highly active combination against human mantle cell lymphoma (MCL) cells. Cancer Biol Ther. 2009 Jul;8(13):1273-80. doi: 10.4161/cbt.8.13.8726.
7 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
8 Schedule-dependent synergy between the heat shock protein 90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and doxorubicin restores apoptosis to p53-mutant lymphoma cell lines. Clin Cancer Res. 2006 Nov 1;12(21):6547-56. doi: 10.1158/1078-0432.CCR-06-1178.