Difference between revisions of "Imetelstat (Rytelo)"

Revision as of 21:23, 26 January 2024

Mechanism of action

From NCI Drug Dictionary: The sodium salt of imetelstat, a synthetic lipid-conjugated, 13-mer oligonucleotide N3' P5'-thio-phosphoramidate with potential antineoplastic activity. Complementary to the template region of telomerase RNA (hTR), imetelstat acts as a competitive enzyme inhibitor that binds and blocks the active site of the enzyme (a "telomerase template antagonist"), a mechanism of action which differs from that for the antisense oligonucleotide-mediated inhibition of telomerase activity through telomerase mRNA binding. Inhibition of telomerase activity in tumor cells by imetelstat results in telomere shortening, which leads to cell cycle arrest or apoptosis. Link to company website

Preliminary data

Essential thrombocythemia

CP14B015: Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Röth A, Daskalakis M, Burington B, Stuart M, Snyder DS. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med. 2015 Sep 3;373(10):920-8. link to original article PubMed NCT01243073

Myelodysplastic syndrome

IMerge: Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1. Erratum in: Lancet. 2024 Jan 20;403(10423):248. link to original article PubMed NCT02598661

Myelofibrosis

CR107110: Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. link to original article PubMed NCT01731951

Also known as

Code name: GRN-163L

@@ Line 3: / Line 3: @@
 ==Preliminary data==
+===[[Essential thrombocythemia]]===
+# '''CP14B015:''' Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Röth A, Daskalakis M, Burington B, Stuart M, Snyder DS. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med. 2015 Sep 3;373(10):920-8. [https://doi.org/10.1056/NEJMoa1503479 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26332546/ PubMed] [https://clinicaltrials.gov/study/NCT01243073 NCT01243073]
+===[[Myelodysplastic syndrome]]===
+#'''IMerge:''' Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1. Erratum in: Lancet. 2024 Jan 20;403(10423):248. [https://doi.org/10.1016/s0140-6736(23)01724-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38048786/ PubMed] [https://clinicaltrials.gov/study/NCT02598661 NCT02598661]
 ===[[Myelofibrosis]]===
 <!-- # '''Abstract:''' Kebede Begna, Rebecca R. Laborde, Mrinal M Patnaik, Terra L Lasho, Darci Zblewski, Christy Finke, Lauren Schimek, Betsy R. LaPlant, Curtis A. Hanson, Monic J. Stuart, Animesh Pardanani. Imetelstat, a Telomerase Inhibitor, Induces Morphologic and Molecular Remissions In Myelofibrosis and Reversal Of Bone Marrow Fibrosis. Blood Nov 2013,122(21)662 [http://www.bloodjournal.org/content/122/21/662 link to original abstract] -->
-# Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. [https://doi.org/10.1056/NEJMoa1310523 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26332545/ PubMed]
+# '''CR107110:''' Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. [https://doi.org/10.1056/NEJMoa1310523 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26332545/ PubMed] [https://clinicaltrials.gov/study/NCT01731951 NCT01731951]
-===[[Essential thrombocythemia]]===
-# Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Röth A, Daskalakis M, Burington B, Stuart M, Snyder DS. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med. 2015 Sep 3;373(10):920-8. [https://doi.org/10.1056/NEJMoa1503479 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26332546/ PubMed]
 ==Also known as==
@@ Line 19: / Line 22: @@
 [[Category:Essential thrombocythemia medications (investigational)]]
+[[Category:Myelodysplastic syndrome medications (investigational)]]
 [[Category:Myelofibrosis medications (investigational)]]
 [[Category:Investigational drugs]]