PMID- 35155195
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220501
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Targeting Thyrointegrin alphavbeta3 Using Fluorobenzyl Polyethylene Glycol Conjugated 
      Tetraiodothyroacetic Acid (NP751) in Acute Myeloid Leukemia.
PG  - 793810
LID - 10.3389/fonc.2021.793810 [doi]
LID - 793810
AB  - BACKGROUND: Acute myeloid leukemia (AML) is associated with poor long-term 
      survival, even with newer therapeutic agents. Here, we show the results of our 
      preclinical study, in which we evaluated the efficacy of a new thyrointegrin alphavbeta3 
      antagonist, named fluorobenzyl polyethylene glycol conjugated 
      tetraiodothyroacetic acid (fb-PMT). METHODS AND RESULTS: fb-PMT (NP751) is a 
      potent alphavbeta3 antagonist of molecular weight of 2,478.9 Da. it represents a 
      conjugate of tetraiodothyroacetic acid (tetrac) and monodisperse polyethylene 
      glycol (PEG36), with a 4-fluorobenzyl group capping the other end of the PEG. 
      fb-PMT effectively suppresses the malignant growth of human acute myeloid 
      leukemia (AML) after successful engraftment in transgenic NSG-S xenograft mouse 
      models of either established human AML cell line or primary AML cells. Daily 
      treatment with fb-PMT (1-10 mg/kg body weight) subcutaneously (s.c.) for 3-4 
      weeks was associated with marked regression of leukemogenesis and extended 
      survival in both models. The efficiency of the fb-PMT therapy was verified using 
      in vivo imaging system (IVIS) imaging, flow cytometry, and histopathological 
      examination to monitor the engraftment of leukemic cells in the bone marrow and 
      other organs. fb-PMT therapy for 3-4 weeks at 3 and 10 mg/kg daily doses 
      exhibited significant reduction (p < 0.0001) of leukemic cell burden of 74% and 
      >95%, respectively. All fb-PMT-treated mice in the 10 mg/kg treatment arm 
      successfully maintained remission after discontinuing the daily treatment. 
      Comprehensive fb-PMT safety assessments demonstrated excellent safety and 
      tolerability at multiple folds above the anticipated human therapeutic doses. 
      Lastly, our genome-wide microarray screens demonstrated that fb-PMT works through 
      the molecular interference mechanism with multiple signaling pathways 
      contributing to growth and survival of leukemic cells. CONCLUSION: Our 
      preclinical findings of the potent anticancer activities of fb-PMT and its 
      favorable safety profiles warrant its clinical investigation for the effective 
      and safe management of AML.
CI  - Copyright (c) 2022 Darwish, Glinsky, Sudha and Mousa.
FAU - Darwish, Noureldien H E
AU  - Darwish NHE
AD  - Pharmaceutical Research Institute, Albany College of Pharmacy and Health 
      Sciences, Rensselaer, NY, United States.
AD  - Hematology Unit, Clinical Pathology Department, Faculty of Medicine, Mansoura 
      University, Mansoura, Egypt.
FAU - Glinsky, Gennadi V
AU  - Glinsky GV
AD  - Institute of Engineering in Medicine, University of California San Diego, San 
      Diego, CA, United States.
FAU - Sudha, Thangirala
AU  - Sudha T
AD  - Pharmaceutical Research Institute, Albany College of Pharmacy and Health 
      Sciences, Rensselaer, NY, United States.
FAU - Mousa, Shaker A
AU  - Mousa SA
AD  - Pharmaceutical Research Institute, Albany College of Pharmacy and Health 
      Sciences, Rensselaer, NY, United States.
LA  - eng
PT  - Journal Article
DEP - 20220127
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8828484
OTO - NOTNLM
OT  - AML
OT  - AML management
OT  - acute myeloid leukemia
OT  - molecular mechanism
OT  - thyrointegrin alphavbeta3
COIS- SM holds several patents on anticancer compounds assigned to NanoPharmaceuticals 
      LLC and founder of the company. GG is a consultant to NanoPharmaceuticals LLC. 
      The remaining authors declare that the research was conducted in the absence of 
      any commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/15 06:00
MHDA- 2022/02/15 06:01
PMCR- 2021/01/01
CRDT- 2022/02/14 05:34
PHST- 2021/10/12 00:00 [received]
PHST- 2021/12/14 00:00 [accepted]
PHST- 2022/02/14 05:34 [entrez]
PHST- 2022/02/15 06:00 [pubmed]
PHST- 2022/02/15 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.793810 [doi]
PST - epublish
SO  - Front Oncol. 2022 Jan 27;11:793810. doi: 10.3389/fonc.2021.793810. eCollection 
      2021.