Details of the Drug

General Information of Drug (ID: DMT8GVU)

Drug Name
177Lu-DOTATATE
Indication
Disease Entry ICD 11 Status REF
Hepatitis C virus infection 1E51.1 Phase 2 [1]
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski):
4		 Molecular Weight 1609.5
Topological Polar Surface Area Not Available
Rotatable Bond Count 23
Hydrogen Bond Donor Count 14
Hydrogen Bond Acceptor Count 26
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
76966897
CAS Number
437608-50-9
TTD ID
D0M5VV

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Somatostatin receptor (SSTR) TTOMNR9 NOUNIPROTAC Modulator [2]
Somatostatin receptor type 4 (SSTR4) TTAE1BR SSR4_HUMAN Inhibitor [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Hepatitis C virus infection
ICD Disease Classification 1E51.1
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Somatostatin receptor type 4 (SSTR4) DTT SSTR4 1.12E-02 -0.07 -0.32
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from 177Lu-DOTATATE (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of 177Lu-DOTATATE and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [20]
Inotersen DMJ93CT Major Increased risk of nephrotoxicity by the combination of 177Lu-DOTATATE and Inotersen. Amyloidosis [5D00] [21]

References

1 ClinicalTrials.gov (NCT01860742) Randomized Phase III of PRRT Versus Interferon. U.S. National Institutes of Health.
2 Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Pancreas. 2014 May;43(4):518-25.
3 New Drug in Development Shows Improved Progression-Free Survival for Patients with Advanced Metastatic Midgut Neuroendocrine Tumors
4 Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012 Feb;39 Suppl 1(Suppl 1):S103-12.
5 DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours.Eur J Endocrinol.2012 Feb;166(2):223-34.
6 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
7 FK960, a novel potential anti-dementia drug, enhances high K(+)-evoked release of somatostatin from rat hippocampal slices. Brain Res. 2001 Feb 16;892(1):111-7.
8 Multimodal Imaging of 2-Cycle PRRT with 177 Lu-DOTA-JR11 and 177 Lu-DOTATOC in an Orthotopic Neuroendocrine Xenograft Tumor Mouse Model. J Nucl Med. 2021 Mar;62(3):393-398.
9 Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020 Sep;19(9):589-608.
10 Clinical pipeline report, company report or official report of Orano Med.
11 Antagonist effects of seglitide (MK 678) at somatostatin receptors in guinea-pig isolated right atria.. Br J Pharmacol. 1993 August; 109(4): 898-899.
12 Somatostatin receptor 1 selective analogues: 3. Dicyclic peptides. J Med Chem. 2005 Jan 27;48(2):515-22.
13 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14 Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196, a putative cognitive enhancer. Eur J Pharmacol. 1993 Sep 7;241(1):27-34.
15 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.
16 Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem. 2005 Jan 27;48(2):507-14.
17 Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. J Med Chem. 2010 Aug 26;53(16):6188-97.
18 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: 358).
19 An adjustable release rate linking strategy for cytotoxin-peptide conjugates. Bioorg Med Chem Lett. 2003 Mar 10;13(5):799-803.
20 Cerner Multum, Inc. "Australian Product Information.".
21 Cerner Multum, Inc. "UK Summary of Product Characteristics.".