NCP26 TFA is an ATP-competitive ProRS inhibitor (with a K D of 271 nM in the absence of proline, and a K D of 0.35 nM in the presence of 100 μM proline). NCP26 TFA activates AAR, induces G0/G1 phase arrest, Apoptosis, Caspase cleavage, and PARP cleavage. NCP26 TFA downregulates MYC, TCF3, and CCND1. NCP26 TFA inhibits the growth of multiple myeloma cells. NCP26 TFA can be used for the research of multiple myeloma [1] [2].
In Vivo, NCP26 (2.5-10 mg/kg; i.p.; once daily; 21 days) TFA significantly inhibits multiple myeloma tumour growth (P = 0.01 and P < 0.001, respectively) and prolongs overall survival (P = 0.01 and P < 0.001, respectively) in CB17 SCID mice bearing AMO1 xenografts, without causing significant body weight loss[1]. NCP26 (10 mg/kg; q.d. [daily]) TFA significantly inhibits multiple myeloma tumor growth (P = 0.005) and prolongs host survival (P < 0.001) in an AMO1 xenograft mouse model without inducing weight loss[2].
In Vitro, NCP26 TFA is an ATP-competitive inhibitor of recombinant ProRS. Its binding affinity increases by more than 750-fold in the presence of 100 μM proline, with a KD of 0.35 nM[1]. NCP26 (0.5 μM; 48 h) TFA maintains antiproliferative activity against AMO1 and RPMI 8226 multiple myeloma (MM) cells over a proline concentration range of 0 to 20 mM, with no reduction in its potency at high proline levels[1]. NCP26 (0.01-10 μM; 96 h) TFA is 10-fold more potent against AMO1 multiple myeloma (MM) cells than against peripheral blood mononuclear cells (PBMCs) from healthy donors, with an EC50 of 0.1 μM for the former and approximately 1 μM for the latter after 96 h of treatment[1]. NCP26 TFA potently inhibits the growth of most multiple myeloma (MM) cell lines, with EC50 values ranging from 135 nM to 1.1 μM[1]. NCP26 (0.5 μM; 6-48 h) TFA induces G0/G1 cell cycle arrest and caspase-dependent apoptosis in AMO1 and RPMI 8226 multiple myeloma (MM) cells[1].
References:
[1]. Kurata K, et al. Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma. Blood Cancer J. 2023;13(1):12. Published 2023 Jan 12.
[2]. Kurata K, et al. Discovery of Prolyl-tRNA Synthetase As a Novel Target in Multiple Myeloma[J]. Blood, 2021, 138: 890.
In Vivo, NCP26 (2.5-10 mg/kg; i.p.; once daily; 21 days) TFA significantly inhibits multiple myeloma tumour growth (P = 0.01 and P < 0.001, respectively) and prolongs overall survival (P = 0.01 and P < 0.001, respectively) in CB17 SCID mice bearing AMO1 xenografts, without causing significant body weight loss[1]. NCP26 (10 mg/kg; q.d. [daily]) TFA significantly inhibits multiple myeloma tumor growth (P = 0.005) and prolongs host survival (P < 0.001) in an AMO1 xenograft mouse model without inducing weight loss[2].
In Vitro, NCP26 TFA is an ATP-competitive inhibitor of recombinant ProRS. Its binding affinity increases by more than 750-fold in the presence of 100 μM proline, with a KD of 0.35 nM[1]. NCP26 (0.5 μM; 48 h) TFA maintains antiproliferative activity against AMO1 and RPMI 8226 multiple myeloma (MM) cells over a proline concentration range of 0 to 20 mM, with no reduction in its potency at high proline levels[1]. NCP26 (0.01-10 μM; 96 h) TFA is 10-fold more potent against AMO1 multiple myeloma (MM) cells than against peripheral blood mononuclear cells (PBMCs) from healthy donors, with an EC50 of 0.1 μM for the former and approximately 1 μM for the latter after 96 h of treatment[1]. NCP26 TFA potently inhibits the growth of most multiple myeloma (MM) cell lines, with EC50 values ranging from 135 nM to 1.1 μM[1]. NCP26 (0.5 μM; 6-48 h) TFA induces G0/G1 cell cycle arrest and caspase-dependent apoptosis in AMO1 and RPMI 8226 multiple myeloma (MM) cells[1].
References:
[1]. Kurata K, et al. Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma. Blood Cancer J. 2023;13(1):12. Published 2023 Jan 12.
[2]. Kurata K, et al. Discovery of Prolyl-tRNA Synthetase As a Novel Target in Multiple Myeloma[J]. Blood, 2021, 138: 890.