Vipivotide tetraxetan

Last updated

Vipivotide tetraxetan
Vipivotide tetraxetan - PSMA-617.svg
Clinical data
Other namesPSMA-617
Identifiers
  • (2S)-2-[[(1S)-1-carboxy-5-[[(2S)-3-naphthalen-2-yl-2-[[4-[[[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]methyl]cyclohexanecarbonyl]amino]propanoyl]amino]pentyl]carbamoylamino]pentanedioic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
Chemical and physical data
Formula C49H71N9O16
Molar mass 1042.154 g·mol−1
3D model (JSmol)
  • C1CC(CCC1CNC(=O)CN2CCN(CCN(CCN(CC2)CC(=O)O)CC(=O)O)CC(=O)O)C(=O)N[C@@H](CC3=CC4=CC=CC=C4C=C3)C(=O)NCCCC[C@@H](C(=O)O)NC(=O)N[C@@H](CCC(=O)O)C(=O)O
  • InChI=InChI=1S/C49H71N9O16/c59-40(28-55-17-19-56(29-42(62)63)21-23-58(31-44(66)67)24-22-57(20-18-55)30-43(64)65)51-27-32-8-12-35(13-9-32)45(68)52-39(26-33-10-11-34-5-1-2-6-36(34)25-33)46(69)50-16-4-3-7-37(47(70)71)53-49(74)54-38(48(72)73)14-15-41(60)61/h1-2,5-6,10-11,25,32,35,37-39H,3-4,7-9,12-24,26-31H2,(H,50,69)(H,51,59)(H,52,68)(H,60,61)(H,62,63)(H,64,65)(H,66,67)(H,70,71)(H,72,73)(H2,53,54,74)/t32?,35?,37-,38-,39-/m0/s1
  • Key:JBHPLHATEXGMQR-VLOIPPKDSA-N

Vipivotide tetraxetan (also known as PSMA-617) is a radiopharmaceutical precursor molecule used in targeted therapies for prostate cancer and other tumors expressing prostate-specific membrane antigen (PSMA).

Contents

PSMA-617 is a high-affinity inhibitor of the peptidase activity of PSMA, with a Ki of 0.37 nM. It consists of a PSMA-targeting moiety conjugated to a high-affinity chelator for metal isotopes. [1] Its strong binding affinity for PSMA allows precise targeting of cancer cells that overexpress this protein, especially in prostate cancer.

Vipivotide tetraxetan is used as a precursor in the synthesis of radiopharmaceuticals such as Lu-PSMA-617 and Ac-PSMA-617. [2] In Lu-PSMA-617, vipivotide tetraxetan chelates the radioactive isotope lutetium-177, a β-emitter used in targeted radioligand therapy. In Ac-PSMA-617, it binds actinium-225, an α-emitter used in targeted alpha-particle therapy.

Chemistry

The compound’s structure includes a PSMA-binding motif (Lys-urea-Glu), a hydrophobic linker (composed of 2-naphthyl-l-Ala and cyclohexyl groups), and a DOTA chelator for radiolabeling. [3]

Nomenclature

Vipivotide tetraxetan is the International Nonproprietary Name (INN) and United States Adopted Name (USAN) for the ligand-targeting and metal-chelating components, respectively, of the radiopharmaceutical drugs Lu-PSMA-617 and Ac-PSMA-617. [4]

"Vipivotide" refers to the peptide-based targeting moiety (Lys-urea-Glu) that binds specifically to prostate-specific membrane antigen (PSMA) on prostate cancer cells. [4] The suffix "tide" denotes the peptide nature of this moiety. [5]

"Tetraxetan" refers to the chelator moiety, a chemical group that binds metal ions within the molecule. The name "tetraxetan" is derived from "tetraazacyclododecane tetra-acetic acid" (DOTA), a well-known macrocyclic chelator that securely holds the radioactive isotope in the drug. The "tetra-" prefix indicates the four nitrogen atoms in the macrocycle and the four acetic acid arms in the DOTA structure, while "xetan" is a standard suffix for chelators. [6]

References

  1. ↑ Schäfer M, Bauder-Wüst U, Roscher M, Motlová L, Kutilová Z, Remde Y, et al. (February 2025). "Structure-Activity Relationships and Biological Insights into PSMA-617 and Its Derivatives with Modified Lipophilic Linker Regions". ACS Omega. 10 (7): 7077–7090. doi:10.1021/acsomega.4c10142. PMC   11865982 . PMID   40028088.
  2. ↑ Ma J, Li L, Liao T, Gong W, Zhang C (2022). "Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis". Frontiers in Oncology. 12: 796657. doi: 10.3389/fonc.2022.796657 . PMC   8852230 . PMID   35186737.
  3. ↑ "Vipivotide tetraxetan". PubChem. U.S. National Library of Medicine.
  4. 1 2 Keam SJ (July 2022). "Lutetium Lu 177 Vipivotide Tetraxetan: First Approval". Molecular Diagnosis & Therapy. 26 (4): 467–475. doi:10.1007/s40291-022-00594-2. PMC   9099330 . PMID   35553387.
  5. ↑ "Guidance on the Use of International Nonproprietary Names (INNs) for Pharmaceutical Substances" (PDF). World Health Organization. 2017. p. 41. -tide peptides and glycopeptides
  6. ↑ "Guidance on the Use of International Nonproprietary Names (INNs) for Pharmaceutical Substances" (PDF). World Health Organization. 2017. p. 42. -xetan chelating agents
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