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. 2021 Dec 31;14(1):191. doi: 10.3390/cancers14010191

Figure 2.

Figure 2

Structures of inhibitors of C1 metabolism. Panel (A): structures are shown for the dual SHMT1 and SHMT2 inhibitors SHIN1 and SHIN2 [150,151], the MTHFD2 inhibitor DS18561882 [152], as well as pemetrexed [137] and CT900 (BGC945, ONX0801) [26] (both principally thymidylate synthase inhibitors). Panel (B): structures are shown for pyrrolo[2,3-d]pyrimidine GARFTase inhibitors, AGF17 [145], AGF23 [145], AGF94 [147], AGF154 [148], AGF278 [149], and AGF283 [149], as well as the pyrrolo[3,2-d]pyrimidine antifolate AGF347 [153], which acts as a multitargeted inhibitor of SHMT2 in the mitochondria and of SHMT1, GARFTase, and ATIC in the cytosol.