| Full text | |
| Author(s): |
Pavan, Aline Renata
;
Lopes, Juliana Romano
;
Dos Santos, Jean Leandro
Total Authors: 3
|
| Document type: | Journal article |
| Source: | EXPERT OPINION ON DRUG DISCOVERY; v. 17, n. 11, p. 15-pg., 2022-11-07. |
| Abstract | |
Introduction: Sickle cell anemia (SCA) is a hematological genetic disorder caused by a mutation in the gene of the beta-globin. Pharmacological treatments will continue to be an important approach, including the strategy to induce fetal hemoglobin (HbF). Areas covered: Here, we analyzed the articles described in the literature regarding the drug discovery of HbF inducers. The main approaches for such strategy will be discussed, highlighting those most promising. Expert opinion: The comprehension of the mechanisms involved in the beta-globin regulation is the main key to design new drugs to induce HbF. Among the strategies, gamma-globin regulation by epigenetic enzymes seems to be a promising approach to be pursued, although the comprehension of the selectivity role for those new drugs is crucial to reduce adverse effects. The low druggability of transcription factors and their vital role in embryonic human development are critical points that should be taken in account for drug design. The guanylate cyclase and the NO/cGMP signaling pathway seem to be promising not only for HbF induction, but also for the protective effects in the cardiovascular system. The association of drugs acting through different mechanisms to induce HbF seems to be promising for the discovery of new drugs. (AU) | |
| FAPESP's process: | 18/19523-7 - Design, synthesis and pharmacological evaluation of hydroxyurea derivatives designed as histone deacetylase inhibitors for Sickle Cell Anemia |
| Grantee: | Aline Renata Pavan |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 21/10059-9 - Synthesis and pharmacological evaluation of PROTAC-HDAC inhibitors-based compounds for sickle cell disease |
| Grantee: | Aline Renata Pavan |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 20/13279-7 - Synthesis and anti-Mycobacterium tuberculosis evaluation of new nitroimidazooxazine derivatives useful for the treatment of multidrug-resistant tuberculosis |
| Grantee: | Jean Leandro dos Santos |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/19531-1 - Targeting histone deacetylase (HDAC-1 and HDAC-2) as mechanisms to induce fetal hemoglobin in sickle cell disease |
| Grantee: | Jean Leandro dos Santos |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 10/12495-6 - Optimization, synthesis and pharmacological evaluation of new drug candidates to treat the symptoms of sickle cell disease |
| Grantee: | Jean Leandro dos Santos |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 12/50359-2 - Design, synthesis and pharmacological evaluation of new hybrid drugs useful to treat hematological disorders |
| Grantee: | Jean Leandro dos Santos |
| Support Opportunities: | Research Grants - Research Partnership for Technological Innovation - PITE |
| FAPESP's process: | 15/21252-3 - Synthesis and Pharmacological evaluation of new thalidomide/pomalidomide analogues regulators of epigenetic mechanisms |
| Grantee: | Aline Renata Pavan |
| Support Opportunities: | Scholarships in Brazil - Master |