CTPS2 (CTP Synthase 2)

Combination of STP-B with pharmacological inhibitors of key components of the DDR pathway (ATR, CHEK1 or WEE1) resulted in synergistic growth inhibition and early apoptosis. Taken together, these findings identify CTPS1 as a promising new target in MM, either alone or in combination with DDR pathway inhibition.

Remarkably, TP53 aberrant and ibrutinib-resistant MCL cells rely on cytidine metabolism... Metabolic Profiling revealed dramatically aberrant cellular abundance of metabolic intermediates in the CTP synthesis pathway. For GSE93291 analysis, a nucleotide metabolism related prognostic model was established by least absolute contraction and selection operator (LASSO) Cox regression analysis and CTPS1 was screened out by highest regression coefficient. Furthermore, IHC staining of CTPS1 in 105 MCL tissues confirmed that elevated CTPS1 expression was significantly associated with poor PFS ( P =0.038) and OS ( P =0.001) in MCL patients ( Figure 1A and B ).

The phase 1 study (NCT05463263) opened to enrolment in the US and UK in September 2022. The phase 2 study will include additional centres in France.

The phase 2 study will include additional centers in France. Clinical trial information: NCT05463263.

These findings identify CTPS1 as a novel therapeutic target in lymphoid malignancy. A compound from this series is in phase 1/2 clinical studies for the treatment of relapsed/refractory B- and T-cell lymphoma (NCT05463263).