Search: onr:"swepub:oai:lup.lub.lu.se:94b22255-73b0-410a-aa43-486e54decfe4" >
Targeting Acute Mye...
Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold : SAR of the Biphenyl Moiety
-
- Sainas, Stefano (author)
- University of Turin
-
- Giorgis, Marta (author)
- University of Turin
-
- Circosta, Paola (author)
- University of Turin
-
show more...
-
- Gaidano, Valentina (author)
- SS. Antonio e Biagio Hospital,University of Turin
-
- Bonanni, Davide (author)
- University of Turin
-
- Pippione, Agnese C. (author)
- University of Turin
-
- Bagnati, Renzo (author)
- Mario Negri Institute for Pharmacological Research
-
- Passoni, Alice (author)
- Mario Negri Institute for Pharmacological Research
-
- Qiu, Yaqi (author)
- Institute for Cancer Research and Treatment, Candiolo,South China University of Technology
-
- Cojocaru, Carina Florina (author)
- Institute for Cancer Research and Treatment, Candiolo
-
Canepa, Barbara (author)
-
Bona, Alessandro (author)
-
- Rolando, Barbara (author)
- University of Turin
-
- Mishina, Mariia (author)
- University of Turin
-
- Ramondetti, Cristina (author)
- University of Turin
-
- Buccinnà, Barbara (author)
- University of Turin
-
- Piccinini, Marco (author)
- University of Turin
-
- Houshmand, Mohammad (author)
- University of Turin
-
- Cignetti, Alessandro (author)
- Mauriziano Hospital, Turin
-
- Giraudo, Enrico (author)
- Institute for Cancer Research and Treatment, Candiolo,University of Turin
-
- Al-Karadaghi, Salam (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
-
- Boschi, Donatella (author)
- University of Turin
-
- Saglio, Giuseppe (author)
- Mauriziano Hospital, Turin,University of Turin
-
- Lolli, Marco L. (author)
- University of Turin
-
show less...
-
University of Turin SS Antonio e Biagio Hospital (creator_code:org_t)
- 2021-04-12
- 2021
- English 25 s.
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:9, s. 5404-5428
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://pubs.acs.org...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound 1, a potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC50 = 32.8 nM) superior to brequinar's phase I/II clinical trial (EC50 = 265 nM). Herein, we investigate the 1 drug-like properties observing good metabolic stability and no toxic profile when administered at doses of 10 and 25 mg/kg every 3 days for 5 weeks (Balb/c mice). Moreover, in order to identify a backup compound, we investigate the SAR of this class of compounds. Inside the series, 17 is characterized by higher potency in inducing myeloid differentiation (EC50 = 17.3 nM), strong proapoptotic properties (EC50 = 20.2 nM), and low cytotoxicity toward non-AML cells (EC30(Jurkat) > 100 μM).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database
- By the author/editor
-
Sainas, Stefano
-
Giorgis, Marta
-
Circosta, Paola
-
Gaidano, Valenti ...
-
Bonanni, Davide
-
Pippione, Agnese ...
-
show more...
-
Bagnati, Renzo
-
Passoni, Alice
-
Qiu, Yaqi
-
Cojocaru, Carina ...
-
Canepa, Barbara
-
Bona, Alessandro
-
Rolando, Barbara
-
Mishina, Mariia
-
Ramondetti, Cris ...
-
Buccinnà, Barbar ...
-
Piccinini, Marco
-
Houshmand, Moham ...
-
Cignetti, Alessa ...
-
Giraudo, Enrico
-
Al-Karadaghi, Sa ...
-
Boschi, Donatell ...
-
Saglio, Giuseppe
-
Lolli, Marco L.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Hematology
- Articles in the publication
-
Journal of Medic ...
- By the university
-
Lund University