HLCL-61 hydrochloride

• CAT Number: I000574
• CAS Number: 1158279-20-9
• Molecular Formula: C₂₃H₂₅ClN₂O
• Molecular Weight: 380.92
• Purity: ≥95%
• Synonyms: 1-(9-ethyl-9H-carbazol-3-yl)-N-(2-methoxybenzyl)methanamine hydrochloride
• Target: Histone Methyltransferase
• Solubility: DMSO: ＞ 30 mg/mL
• Storage: Store at -20°C
• IUPAC Name: 1-(9-ethylcarbazol-3-yl)-N-[(2-methoxyphenyl)methyl]methanamine;hydrochloride
• InChI: InChI=1S/C23H24N2O.ClH/c1-3-25-21-10-6-5-9-19(21)20-14-17(12-13-22(20)25)15-24-16-18-8-4-7-11-23(18)26-2;/h4-14,24H,3,15-16H2,1-2H3;1H
• InChIKey: XYAVCNMZZKTEGR-UHFFFAOYSA-N
• SMILES: CCN1C2=C(C=C(C=C2)CNCC3=CC=CC=C3OC)C4=CC=CC=C41.Cl

HLCL-61 hydrochloride（Cat No.:I000574）is a selective inhibitor of the protein kinase CK2 (casein kinase 2), which is involved in various cellular processes, including cell proliferation, apoptosis, and DNA repair. By inhibiting CK2, HLCL-61 disrupts critical signaling pathways associated with cancer progression and survival. This compound has demonstrated potential anti-cancer activity in preclinical studies, particularly in solid tumors and hematologic malignancies characterized by elevated CK2 activity. HLCL-61 hydrochloride’s unique mechanism of action provides valuable insights into CK2’s role in tumor biology, making it a promising candidate for developing targeted cancer therapies.

Reference

1. Leukemia. 2016 Apr;30(4):789-99. doi: 10.1038/leu.2015.308. Epub 2015 Nov 5.
The dual epigenetic role of PRMT5 in acute myeloid leukemia: gene activation and repression via histone arginine methylation.
Tarighat SS(1), Santhanam R(2), Frankhouser D(2), Radomska HS(2), Lai H(3), Anghelina M(2), Wang H(2), Huang X(1), Alinari L(2), Walker A(2), Caligiuri MA(2), Croce CM(4), Li L(5), Garzon R(2), Li C(3), Baiocchi RA(2), Marcucci G(5).
Author information:
(1)Molecular, Cellular, and Developmental Biology Graduate Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. (2)Division of Hematology, Department of Medicine, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. (3)Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA. (4)Department of Molecular Virology, Immunology and Cancer Genetics, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. (5)Gehr Family Leukemia Center, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Changes in the enzymatic activity of protein arginine methyltransferase (PRMT) 5 have been associated with cancer; however, the protein/’s role in acute myeloid leukemia (AML) has not been fully evaluated. Here, we show that increased PRMT5 activity enhanced AML growth in vitro and in vivo while PRMT5 downregulation reduced it. In AML cells, PRMT5 interacted with Sp1 in a transcription repressor complex and silenced miR-29b preferentially via dimethylation of histone 4 arginine residue H4R3. As Sp1 is also a bona fide target of miR-29b, the miR silencing resulted in increased Sp1. This event in turn led to transcription activation of FLT3, a gene that encodes a receptor tyrosine kinase. Inhibition of PRMT5 via sh/siRNA or a first-in-class small-molecule inhibitor (HLCL-61) resulted in significantly increased expression of miR-29b and consequent suppression of Sp1 and FLT3 in AML cells. As a result, significant antileukemic activity was achieved. Collectively, our data support a novel leukemogenic mechanism in AML where PRMT5 mediates both silencing and transcription of genes that participate in a /’yin-yang/’ functional network supporting leukemia growth. As FLT3 is often mutated in AML and pharmacologic inhibition of PRMT5 appears feasible, the PRMT5-miR-29b-FLT3 network should be further explored as a novel therapeutic target for AML.