DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS
El-Zahabi, M., Abouzeid, M., Eissa, I., Taghour, M. (2024). DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS. EKB Journal Management System, 69(1), 38-61. doi: 10.21608/ajps.2024.360357
Mohamed Ayman ALy El-Zahabi; Mostafa Youssef Abouzeid; Ibrahim H Eissa; Mohamed S Taghour. "DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS". EKB Journal Management System, 69, 1, 2024, 38-61. doi: 10.21608/ajps.2024.360357
El-Zahabi, M., Abouzeid, M., Eissa, I., Taghour, M. (2024). 'DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS', EKB Journal Management System, 69(1), pp. 38-61. doi: 10.21608/ajps.2024.360357
El-Zahabi, M., Abouzeid, M., Eissa, I., Taghour, M. DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS. EKB Journal Management System, 2024; 69(1): 38-61. doi: 10.21608/ajps.2024.360357

DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS

Al-Azhar Journal of Pharmaceutical Sciences
Volume 69, Issue 1, March 2024, Page 38-61  XML PDF (823.51 K)
Document Type: Original Article
DOI: 10.21608/ajps.2024.360357
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Authors
Mohamed Ayman ALy El-Zahabi email orcid 1; Mostafa Youssef Abouzeid1; Ibrahim H Eissa1; Mohamed S Taghour2
1Pharmaceutical Medicinal Chemistry& Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
2Pharmaceutical Medicinal Chemistry& Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt
Abstract
Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are enzymes that catalyze the rate-limiting step of the kynurenine pathway. Recent literature reports IDO and TDO upregulation in tumor cells leading to L-tryptophan depletion and accumulation of tryptophan metabolites. This process represents an essential mechanism for tumor-induced immunosuppression. Following the failure of Epacadostat, an IDO inhibitor, in phase 3 clinical trials, numerous studies have shifted to a dual inhibition scheme to overcome the compensation mechanism linked to TDO. Therefore, the dual inhibition of IDO and TDO using a single molecule emerges as a highly promising therapeutic approach. This comprehensive review aims to discuss the successful scaffolds of reported dual inhibitors and their inhibitory values against both enzymes. The reported active compounds have the potential to form a novel chemical class of anti-tumor immune modulator drugs.
Keywords
Indoleamine-2; tryptophan-2; 3-dioxygenase; dual inhibitors; anti-tumor immune modulators
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