Lutetium Lu 177 dotatate

DCTPepD ID  DCTPepD0013

Active Ingredients   Lutetium Lu 177 dotatate

Description  A radioconjugate consisting of the tyrosine-containing somatostatin analog Tyr3-octreotate (TATE) conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and radiolabeled with the beta-emitting radioisotope lutetium Lu 177, with potential imaging and antineoplastic activities. Lutetium Lu 177 dotatate belongs to an emerging form of treatments called Peptide Receptor Radionuclide Therapy (PRRT), which involves targeting tumours with molecules carrying radioactive particles that bind to specific receptors expressed by the tumour. Lutetium Lu 177 dotatate binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. Tyr3-octreotate (TATE) is an octreotide derivative in which phenylalanine at position 3 is substituted by tyrosine and position 8 threoninol is replaced with threonine. SSTRs have been shown to be present in large numbers on NET and their metastases, while most other normal tissues express low levels of SSTRs.

Synonyms  177Lu-DOTA-octreotate; 177Lu-dotatate; Dotatate lutenium Lu-177; Lu-DOTA-TATE; Lutetium dotatate Lu-177;; Lutetium Lu 177 dotatate

Disease  Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Classification

  

Somatostatin and analogues Peptide and derivative Cyclic Peptide Receptor Radionuclide Therapy(PPRT) Cancer targeted Radioconjugates

Structure Information


Molecular Formula  C65H87LuN14O19S2

Molecular Weight  1609.5

Active Sequence  Not available

Sequence Length  Not available

Modification  Not available

Structure

 

Show IUPAC/InChI/SMILES

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+)

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

InChI_Key MXDPZUIOZWKRAA-PRDSJKGBSA-K

SMILES  C[C@H]([C@@H](C(O)=O)NC([C@@H]1CSSC[C@@H](C(N[C@H](C(N[C@@H](C(N[C@H](C(N[C@H](C(N1)=O)[C@H](O)C)=O)CCCCN)=O)CC2=CNC3=C2C=CC=C3)=O)CC4=CC=C(C=C4)O)=O)NC([C@H](NC(CN5CCN(CCN(CCN(CC5)CC([O-])=O)CC([O-])=O)CC([O-])=O)=O)CC6=CC=CC=C6)=O)=O)O.[177Lu+3]

External Codes


PubChem CID  76966897

DrugBank Accession Number  DB13985

NCI Thesaurus Code  C95020  

UNII  AE221IM3BB   GSRS

CAS  437608-50-9



Drug approval


Drug indication
    Indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Drug Name Strength Dosage Form/Route Company Marketing Status Drug ID Approval year
Lutathera 10mci/ml Solution; Intravenous Aaa Usa Inc Prescription NDA: 208700 2018
Lutathera unknown Infusion; Intravenous Advanced Accelerator Applications Prescription EMEA/H/C/004123 2017

ClinicalTrials.gov Identifier Title Condition or disease Phase Purpose
NCT03972488 A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET Gastro-enteropancreatic Neuroendocrine Tumor Phase 3 Treatment
NCT01456078 A Multicenter Phase II-Study Evaluating Efficacy and Safety of 177Lu-DOTA-TATE Based on Kidney-Dosimetry in Patients With Disseminated Neuroendocrine Tumors Neuroendocrine Tumors; Liver Metastases Phase 2 Treatment
NCT03325816 Phase I/II Trial of Anti-PD-1 Checkpoint Inhibitor Nivolumab and 177Lu-DOTA0-Tyr3-Octreotate for Patients With Extensive-Stage Small Cell Lung Cancer Small Cell Lung Cancer; Small Cell Lung Cancer Extensive Stage Phase 1/2 Treatment
NCT04750954 A Phase 1b Trial of M3814 (Peposertib) in Combination With Lutetium 177 Dotatate for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) Neuroendocrine Neoplasm Phase 1 Treatment
NCT03971461 A Single Arm, Open-label, Multicenter Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma Meningioma Phase 2 Treatment

    More clinical information is obtained from ClinicalTrials.gov.





DCTPep is developed by Dr.Zheng's team.