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. 2022 Jun 10;12(6):815. doi: 10.3390/biom12060815

Table 1.

FDA-approved hRR inhibitors and their anticancer applications.

Structure Name Cellular
Mechanism		 RR
Subunit Targeted		 Mechanism of RR
Inhibition		 Indications: Single Agent Indications: Combination
graphic file with name biomolecules-12-00815-i001.jpg Fludarabine Interferes with DNA synthesis and repair mechanisms hRRM1 Induces formation of inactive a6 hexamers Chronic lymphocytic
leukemia		 With cyclophosphamide, mitoxantrone, dexamethasone, and rituximab: non-Hodgkin’s lymphoma
With cyclophosphamide, mitoxantrone, dexamethasone, and granulocyte colony-stimulating factor: acute myeloid leukemia
graphic file with name biomolecules-12-00815-i002.jpg Cladribine Interferes with DNA synthesis and repair mechanisms hRRM1 Induces formation of inactive a6 hexamers Hairy cell leukemia B-cell chronic lymphocytic leukemic
graphic file with name biomolecules-12-00815-i003.jpg Gemcitabine Interferes with DNA synthesis and repair mechanisms hRRM1 Alkylates the C-site irreversibly Pancreatic cancer Off label: cholangiocarcinoma and other biliary tract cancers With nab-paclitaxel: pancreatic cancer
With cisplatin: advanced or metastatic bladder cancer; advanced or metastatic non-small cell lung cancer
With carboplatin: ovarian cancer
With paclitaxel: metastatic breast cancer
graphic file with name biomolecules-12-00815-i004.jpg Clofarabine Interferes with DNA synthesis and repair mechanisms hRRM1 Induces formation of inactive a6 hexamers Relapsed or refractory acute lymphoblastic leukemia
graphic file with name biomolecules-12-00815-i005.jpg Hydroxyurea Radical Scavenger hRRM2 Quenches the radical center Chronic myelogenous leukemia