L 741742

L 741742 is a highly selective and brain-penetrant D4 dopamine receptor antagonist, with K_i values of 3.5 nM, 770 nM and >1700 nM for human D4, D3 and D2 receptors, respectively. L 741742 suppresses PDGFRβ, ERK1/2, and mTOR signaling pathways, and impairs autophagic flux while disrupting lysosomal function.L 741742 induces G0/G1 cell-cycle arrest and apoptosis, promotes neuronal differentiation of normal human neural stem cells, selectively inhibits growth and clonogenic potential of glioblastoma neural stem cells and primary glioblastoma tumor cells, exerts synergistic effects with Temozolomide (TMZ) (HY-17364) against glioblastoma neural stem cells in vitro, and inhibits glioblastoma neural stem cell xenograft growth in immunocompromised mice. L 741742 can be used for the research of schizophrenia and glioblastoma^[1][2]. In Vitro:L 741742 (compound 36) is a high-affinity, selective antagonist for hD4 receptors with a K_i of 3.5 nM, >500-fold selectivity over hD2 receptors, and >200-fold selectivity over hD3 receptors^[1].
L 741742 (1.5-6.2 μM; 5 days) selectively inhibits the growth of patient-derived glioblastoma neural stem cells (GNS) with an IC₅₀ of 1.5-6.2 μM and shows minimal activity against non-neural stem cell lines^[2].
L 741742 (10 μM; 14 days) potently reduces the clonogenic potential of freshly isolated patient-derived glioblastoma tumor cells by 40- to 83-fold^[3].
L 741742 (3 weeks) promotes neuronal differentiation of normal human neural stem cells, as indicated by increased VGlut1 expression^[2].
L 741742 (10 μM; 48 hr) induces massive accumulation of autophagosomes in G411 and G362 glioblastoma neural stem cells, as shown by increased LC3B-II levels and LC3B⁺ puncta^[2].
L 741742 (10 μM; 48 hr) impairs autophagic flux in G411 glioblastoma neural stem cells, as indicated by blocked LC3B-II turnover in the presence of Chloroquine (HY-17589A)^[2].
L 741742 (10 μM) inhibits the PDGFRβ-ERK1/2 and mTOR signaling pathways in glioblastoma neural stem cells, as shown by reduced phosphorylation of ERK1/2, PDGFRβ, and S6^[2].
L 741742 (10 μM; 48 hr) induces G₀/G₁ cell cycle arrest and subsequent apoptosis in G411 and G362 glioblastoma neural stem cells^[2]. In Vivo:L 741742 (20 mg/kg; i.p.; 5 days on, 2 days off) significantly inhibits subcutaneous glioblastoma xenograft growth by 40.9% and reduces tumor stem cell frequency in NSG mice^[2].
L 741742 (25 mg/kg; i.p.; 5 days on, 2 days off; 2 weeks) provides a significant survival benefit in mice with intracranial glioblastoma xenografts^[2].