Details of the Drug

General Information of Drug (ID: DMN1XVC)

Drug Name
Lutetium Lu 177 dotatate
Synonyms UNII-AE221IM3BB; Dotatate lutenium Lu-177; AE221IM3BB; Lu-DOTA-TATE; 177Lu-DOTA-octreotate; Lutetium Lu 177 Dotatate; 177Lu-DOTA-Tyr3-octreotate
Indication
Disease Entry ICD 11 Status REF
Neuroendocrine cancer 2B72.1 Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski):
4		 Molecular Weight 1609.5
Topological Polar Surface Area Not Available
Rotatable Bond Count 18
Hydrogen Bond Donor Count 14
Hydrogen Bond Acceptor Count 26
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 41 mcgh/L [2]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 10 mcg/L [2]
Clearance
The clearance of drug is 4.5 L/h [3]
Elimination
Lutetium Lu 177 dotatate predominantly undergoes renal excretion with cumulative excretion of 44% within 5 hours, 58% within 24 hours, and 65% within 48 hours following intravenous administration [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 3.5 +/- 1.4 hours [2]
Metabolism
The drug is not metabolised [2]
Vd
The volume of distribution (Vd) of drug is 460 L [3]
Chemical Identifiers
Formula
C65H87LuN14O19S2
IUPAC Name
2-[4-[2-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-[[(1S,2R)-1-carboxy-2-hydroxypropyl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate;lutetium-177(3+)
Canonical SMILES
C[C@H]([C@H]1C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N1)CCCCN)CC2=CNC3=CC=CC=C32)CC4=CC=C(C=C4)O)NC(=O)[C@@H](CC5=CC=CC=C5)NC(=O)CN6CCN(CCN(CCN(CC6)CC(=O)[O-])CC(=O)[O-])CC(=O)[O-])C(=O)N[C@@H]([C@@H](C)O)C(=O)O)O.[177Lu+3]
InChI
InChI=1S/C65H90N14O19S2.Lu/c1-38(80)56-64(96)73-51(63(95)75-57(39(2)81)65(97)98)37-100-99-36-50(72-59(91)47(28-40-10-4-3-5-11-40)68-52(83)32-76-20-22-77(33-53(84)85)24-26-79(35-55(88)89)27-25-78(23-21-76)34-54(86)87)62(94)70-48(29-41-15-17-43(82)18-16-41)60(92)71-49(30-42-31-67-45-13-7-6-12-44(42)45)61(93)69-46(58(90)74-56)14-8-9-19-66;/h3-7,10-13,15-18,31,38-39,46-51,56-57,67,80-82H,8-9,14,19-30,32-37,66H2,1-2H3,(H,68,83)(H,69,93)(H,70,94)(H,71,92)(H,72,91)(H,73,96)(H,74,90)(H,75,95)(H,84,85)(H,86,87)(H,88,89)(H,97,98);/q;+3/p-3/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+;/m1./s1/i;1+2
InChIKey
MXDPZUIOZWKRAA-PRDSJKGBSA-K
Cross-matching ID
PubChem CID
132274234
CAS Number
437608-50-9
DrugBank ID
DB13985
TTD ID
D0DQ7V

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Somatostatin receptor type 1 (SSTR1) TTIND6G SSR1_HUMAN Antagonist [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Neuroendocrine cancer
ICD Disease Classification 2B72.1
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Somatostatin receptor type 1 (SSTR1) DTT SSTR1 2.39E-14 -0.6 -0.83
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
2 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
3 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 355).
5 Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22.
6 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
7 Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from ... J Med Chem. 2005 Oct 20;48(21):6643-52.
8 Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14.
9 Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. J Med Chem. 2010 Aug 26;53(16):6188-97.
10 An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.