Minigastrin

Last updated
Minigastrin
Minigastrin.png
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C74H99N15O26S/c1-37(2)30-44(75)65(106)81-47(19-24-58(94)95)68(109)83-49(21-26-60(98)99)70(111)85-50(22-27-61(100)101)71(112)84-48(20-25-59(96)97)69(110)82-46(18-23-57(92)93)67(108)79-38(3)64(105)88-53(32-40-14-16-42(90)17-15-40)66(107)78-36-56(91)80-54(33-41-35-77-45-13-9-8-12-43(41)45)73(114)86-51(28-29-116-4)72(113)89-55(34-62(102)103)74(115)87-52(63(76)104)31-39-10-6-5-7-11-39/h5-17,35,37-38,44,46-55,77,90H,18-34,36,75H2,1-4H3,(H2,76,104)(H,78,107)(H,79,108)(H,80,91)(H,81,106)(H,82,110)(H,83,109)(H,84,112)(H,85,111)(H,86,114)(H,87,115)(H,88,105)(H,89,113)(H,92,93)(H,94,95)(H,96,97)(H,98,99)(H,100,101)(H,102,103)/t38-,44-,46-,47-,48-,49-,50-,51-,52-,53-,54-,55-/m0/s1 X mark.svgN
    Key: HRSUIUNCTPSRLR-SOLHVGTRSA-N X mark.svgN
  • C[C@@H](C(=O)N[C@@H](Cc1ccc(cc1)O)C(=O)NCC(=O)N[C@@H](Cc2c[nH]c3c2cccc3)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc4ccccc4)C(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)N
Properties
C70H91N15O26
Molar mass 1558.56 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Minigastrin (also mini gastrin) is a form of gastrin. Its sequence is H-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2. [1]

Minigastrin is a potential therapeutic agent for thyroid carcinoma by targeting cancer-promoting cholecystokinin receptors. [2]

Applications

Peptide Receptor Radionuclide Therapy (PRRT)

A radioactively labeled analogue of minigastrin, PP-F11, conjugated with NOTA, DOTA, or NODAGA, was studied to view the effects they have on peptide receptor radionuclide therapy (PRRT) and cancer cell tracing. [3] When mice with CCK2 tumors were injected with 64Cu-labeled DOTA-PP-F11, NOTA-PP-F11, and NODAGA-PP-F11, the mice labeled with NOTA displayed a tumor uptake of 7.20 ± 0.44% ID/g and a high tumor-to-blood ratio. [4] Further studies are being investigated on how to reduce the background levels to obtain clearer images.

The inhibition of rapamycin complex 1 improves the tumor uptake of radioactively labeled minigastrin. Treatment of A431/CCKBR tumor cells were assessed with DOTA-PP-F11N. [5] This treatment in combination with RAD001 in mice, resulted in an average size tumor reduction of about 0.3 cm³ in comparison to the control group which had an average tumor size of 0.97 cm³. [6] The treatment group also had a higher survival rate where the control group median life span was 19.5 days and the group that received treatment had an average life span of 43 days. [7]

Related Research Articles

<span class="mw-page-title-main">Octreotide</span> Octapeptide that mimics natural somatostatin pharmacologically

Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer, and binds predominantly to the somatostatin receptors SSTR2 and SSTR5.

Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to neuroendocrine tumors. The syndrome is caused by neuroendocrine tumors most often found in the gut releasing biologically active substances into the blood causing symptoms such as flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction.

<span class="mw-page-title-main">Triptorelin</span> GnRH-agonist

Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga-PSMA is used for cancer imaging. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET).

<span class="mw-page-title-main">Fenobam</span> Chemical compound

Fenobam is an imidazole derivative developed by McNeil Laboratories in the late 1970s as a novel anxiolytic drug with an at-the-time-unidentified molecular target in the brain. Subsequently, it was determined that fenobam acts as a potent and selective negative allosteric modulator of the metabotropic glutamate receptor subtype mGluR5, and it has been used as a lead compound for the development of a range of newer mGluR5 antagonists.

Minretumomab (CC49) is a mouse monoclonal antibody that was designed for the treatment of cancers that express the TAG-72 antigen. This includes breast, colon, lung, and pancreatic cancers. Apparently, it never got past Phase I clinical trials for this purpose.

Copper-64 (64Cu) is a positron and beta emitting isotope of copper, with applications for molecular radiotherapy and positron emission tomography. Its unusually long half-life (12.7-hours) for a positron-emitting isotope makes it increasingly useful when attached to various ligands, for PET and PET-CT scanning.

<span class="mw-page-title-main">Iobenguane</span> Chemical compound

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine (noradrenaline), typically used as a radiopharmaceutical. It acts as a blocking agent for adrenergic neurons. When radiolabeled, it can be used in nuclear medicinal diagnostic and therapy techniques as well as in neuroendocrine chemotherapy treatments.

Scandium-44 (44Sc) is a radioactive isotope of scandium that decays by positron emission to stable 44Ca with a half-life of 4.042 hours.

<span class="mw-page-title-main">DOTA-TATE</span> Eight amino-acid long peptide covalently bonded to a DOTA chelator

DOTA-TATE is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.

<span class="mw-page-title-main">Edotreotide</span> Chemical compound

Edotreotide (USAN, also known as (DOTA0-Phe1-Tyr3) octreotide, DOTA-TOC, DOTATOC) is a substance which, when bound to various radionuclides, is used in the treatment and diagnosis of certain types of cancer. When used therapeutically it is an example of peptide receptor radionuclide therapy.

<span class="mw-page-title-main">Lilotomab</span> Murine monoclonal antibody against CD37

Lilotomab is a murine monoclonal antibody against CD37, a glycoprotein which is expressed on the surface of mature human B cells. It was generated at the Norwegian Radium Hospital.

Advanced Accelerator Applications is a France-based pharmaceutical group, specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine to diagnose and treat serious conditions in the fields of oncology, neurology, cardiology, infectious and inflammatory diseases.

<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Lutetium (<sup>177</sup>Lu) chloride Radioactive compound used for radiopharmaceutical labeling

Lutetium (177Lu) chloride is a radioactive compound used for the radiolabeling of pharmaceutical molecules, aimed either as an anti-cancer therapy or for scintigraphy. It is an isotopomer of lutetium(III) chloride containing the radioactive isotope 177Lu, which undergoes beta decay with a half-life of 6.65 days.

Lutetium (<sup>177</sup>Lu) oxodotreotide Chelate of Lu-177 with DOTA-TATE, a peptide derivative bound to a DOTA molecule

Lutetium (177Lu) oxodotreotide (INN) or 177Lu DOTA-TATE, trade name Lutathera, is a chelated complex of a radioisotope of the element lutetium with DOTA-TATE, used in peptide receptor radionuclide therapy (PRRT). Specifically, it is used in the treatment of cancers which express somatostatin receptors.

Lutetium (<sup>177</sup>Lu) vipivotide tetraxetan Radiopharmaceutical medication

Lutetium (177Lu) vipivotide tetraxetan, sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.

<span class="mw-page-title-main">Somatostatin receptor antagonist</span> Class of chemical compounds

Somatostatin receptor antagonists are a class of chemical compounds that work by imitating the structure of the neuropeptide somatostatin. The somatostatin receptors are G protein-coupled receptors. Somatostatin receptor subtypes in humans are sstr1, 2A, 2 B, 3, 4 and 5. While normally expressed in the gastrointestinal (GI) tract, pancreas, hypothalamus, and central nervous system (CNS), they are expressed in different types of tumours. The predominant subtype in cancer cells is the ssrt2 subtype, which is expressed in neuroblastomas, meningiomas, medulloblastomas, breast carcinomas, lymphomas, renal cell carcinomas, paragangliomas, small cell lung carcinomas and hepatocellular carcinomas.

<span class="mw-page-title-main">Somatostatin inhibitor</span> Class of pharmaceuticals

Somatostatin receptor antagonists are a class of chemical compounds that work by imitating the structure of the neuropeptide somatostatin, which is an endogenous hormone found in the human body. The somatostatin receptors are G protein-coupled receptors. Somatostatin receptor subtypes in humans include sstr1, 2A, 2 B, 3, 4, and 5. While normally expressed in the gastrointestinal (GI) tract, pancreas, hypothalamus, and central nervous system (CNS), they are expressed in different types of tumours. The predominant subtype in cancer cells is the ssrt2 subtype, which is expressed in neuroblastomas, meningiomas, medulloblastomas, breast carcinomas, lymphomas, renal cell carcinomas, paragangliomas, small cell lung carcinomas, and hepatocellular carcinomas.

Theranostics, also known as theragnostics, is an emerging field in precision medicine that combines diagnostic and therapeutic approaches to provide the potential for personalized treatment and real-time monitoring of the effectiveness of treatments. Improvements in imaging techniques and targeted therapies are the basis of the field of theranostics. When medical imaging is coupled with the development of novel radiotracers and contrast agents, theranostics may provide opportunities for precise diagnosis and targeted therapy.

References

  1. Oxford dictionary of biochemistry and molecular biology (Rev. ed.). Oxford University Press. 29 June 2006. ISBN   9780198529170.
  2. von Guggenberg, Elisabeth; Rangger, Christine; Sosabowski, Jane; Laverman, Peter; Reubi, Jean-Claude; Virgolini, Irene Johanna; Decristoforo, Clemens (6 July 2011). "Preclinical Evaluation of Radiolabeled DOTA-Derivatized Cyclic Minigastrin Analogs for Targeting Cholecystokinin Receptor Expressing Malignancies". Molecular Imaging and Biology. 14 (3): 366–375. doi:10.1007/s11307-011-0506-2. PMID   21732165. S2CID   20362994.
  3. Roosenburg, S.; Laverman, P.; Joosten, L.; Cooper, M. S.; Kolenc-Peitl, P. K.; Foster, J. M.; Hudson, C.; Leyton, J.; Burnet, J.; Oyen, W. J. G.; Blower, P. J. (2014-11-03). "PET and SPECT Imaging of a Radiolabeled Minigastrin Analogue Conjugated with DOTA, NOTA, and NODAGA and Labeled with 64 Cu, 68 Ga, and 111 In". Molecular Pharmaceutics. 11 (11): 3930–3937. doi:10.1021/mp500283k. ISSN   1543-8384. PMID   24992368.
  4. Roosenburg, S.; Laverman, P.; Joosten, L.; Cooper, M. S.; Kolenc-Peitl, P. K.; Foster, J. M.; Hudson, C.; Leyton, J.; Burnet, J.; Oyen, W. J. G.; Blower, P. J. (2014-11-03). "PET and SPECT Imaging of a Radiolabeled Minigastrin Analogue Conjugated with DOTA, NOTA, and NODAGA and Labeled with 64 Cu, 68 Ga, and 111 In". Molecular Pharmaceutics. 11 (11): 3930–3937. doi:10.1021/mp500283k. ISSN   1543-8384. PMID   24992368.
  5. Grzmil, Michal; Imobersteg, Stefan; Blanc, Alain; Frank, Stephan; Schibli, Roger; Béhé, Martin P. (2021-12-15). "Therapeutic Response of CCKBR-Positive Tumors to Combinatory Treatment with Everolimus and the Radiolabeled Minigastrin Analogue [177Lu]Lu-PP-F11N". Pharmaceutics. 13 (12): 2156. doi: 10.3390/pharmaceutics13122156 . ISSN   1999-4923. PMC   8708304 . PMID   34959437.
  6. Grzmil, Michal; Imobersteg, Stefan; Blanc, Alain; Frank, Stephan; Schibli, Roger; Béhé, Martin P. (2021-12-15). "Therapeutic Response of CCKBR-Positive Tumors to Combinatory Treatment with Everolimus and the Radiolabeled Minigastrin Analogue [177Lu]Lu-PP-F11N". Pharmaceutics. 13 (12): 2156. doi: 10.3390/pharmaceutics13122156 . ISSN   1999-4923. PMC   8708304 . PMID   34959437.
  7. Grzmil, Michal; Imobersteg, Stefan; Blanc, Alain; Frank, Stephan; Schibli, Roger; Béhé, Martin P. (2021-12-15). "Therapeutic Response of CCKBR-Positive Tumors to Combinatory Treatment with Everolimus and the Radiolabeled Minigastrin Analogue [177Lu]Lu-PP-F11N". Pharmaceutics. 13 (12): 2156. doi: 10.3390/pharmaceutics13122156 . ISSN   1999-4923. PMC   8708304 . PMID   34959437.