L 741742 hydrochloride 

L 741742 hydrochloride 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 hydrochloride suppresses PDGFRβ, ERK1/2, and mTOR signaling pathways, and impairs autophagic flux while disrupting lysosomal function.L 741742 hydrochloride 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 hydrochloride can be used for the research of schizophrenia and glioblastoma^[1][2].

L 741742 (compound 36) hydrochloride 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) hydrochloride 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) hydrochloride potently reduces the clonogenic potential of freshly isolated patient-derived glioblastoma tumor cells by 40- to 83-fold^[3].
L 741742 (3 weeks) hydrochloride promotes neuronal differentiation of normal human neural stem cells, as indicated by increased VGlut1 expression^[2].
L 741742 (10 μM; 48 hr) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride induces G₀/G₁ cell cycle arrest and subsequent apoptosis in G411 and G362 glioblastoma neural stem cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

L 741742 (20 mg/kg; i.p.; 5 days on, 2 days off) hydrochloride 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) hydrochloride provides a significant survival benefit in mice with intracranial glioblastoma xenografts^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

417.37

C₂₃H₂₆Cl₂N₂O

874882-93-6

CC1=C(C2=CC=C(Cl)C=C2)ON=C1C3CCN(CCC4=CC=CC=C4)CC3.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Rowley M, et al. 4-Heterocyclylpiperidines as selective high-affinity ligands at the human dopamine D4 receptor. J Med Chem. 1997;40(15):2374-2385.  [Content Brief]

  [2]. Dolma S, et al. Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells. Cancer Cell. 2016;29(6):859-873.  [Content Brief]