WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406748
CAS#: 1158279-20-9 (HCl)
Description: HLCL-61 is a potent and selective PRMT5 inhibitor for treatment of acute myeloid leukemia. HLCL-61 resulted in significantly increased expression of miR-29b and consequent suppression of Sp1 and FLT3 in AML (acute myeloid leukemia) cells. As a result, significant antileukemic activity was achieved. The 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.
Hodoodo Cat#: H406748
Name: HLCL-61 HCl
CAS#: 1158279-20-9 (HCl)
Chemical Formula: C23H25ClN2O
Exact Mass: 344.19
Molecular Weight: 380.916
Elemental Analysis: C, 72.52; H, 6.62; Cl, 9.31; N, 7.35; O, 4.20
Related CAS #: 1158279-20-9 (HCl) 586395-74-6 (free base)
Synonym: HLCL61; HLCL 61; HLCL-61.
IUPAC/Chemical Name: 1-(9-ethyl-9H-carbazol-3-yl)-N-(2-methoxybenzyl)methanamine hydrochloride
InChi Key: XYAVCNMZZKTEGR-UHFFFAOYSA-N
InChi Code: 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
SMILES Code: COC1=CC=CC=C1CNCC2=CC3=C(C=C2)N(CC)C4=C3C=CC=C4.[H]Cl
Appearance: White to off white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Related CAS# 586395-74-6 (HLCL-61 free base). 1158279-20-9 (HLCL-61 hydrochloride)
| Biological target: | HLCL-61 hydrochloride is a first-in-class inhibitor of protein arginine methyltransferase 5 (PRMT5). |
| In vitro activity: | Using an in vitro enzyme assay to measure methylase activity, HLCL-61 was determined as one of the most potent of the selected inhibitors (Supplementary Figure S3B). HLCL-61 showed no inhibitory activity against the type I (PRMT1 and PRMT4) and type II (PRMT7) PRMT family members (Supplementary Figure S3B), thus indicating its specificity for PRMT5. HLCL-61 showed effective inhibition of symmetric arginine dimethylation (me2) of histones H3 and H4 in AML samples, starting at 12 hours post-treatment and persisting after 48 hours (Figure 3A). Treatment of AML cell lines (MV4–11 and THP-1) and primary blasts with HLCL-61 also resulted in a decrease of cell viability (Figure 3B). Colony forming assays also demonstrated decreased clonogenic activity (>2.2 fold, as compared to DMSO-treated cells) of MV4–11, THP-1, and patient blasts (Patient #1; FLT3-ITD and Patient #2; FLT3-WT) treated with HLCL-61, even at concentrations as low as 100 nM (Figure 3C). HLCL-61 was also effective in promoting apoptosis in MV4–11 and THP-1 cells after 48 hours (Figure 3D).To determine whether HLCL-61 could induce myeloid differentiation, CD11b expression was tested by flow cytometry on cells treated with DMSO or HLCL-61 (25 and 50 μM) for 48 hours. HLCL-61–treated AML cell lines and patient samples exhibited induction of differentiation as suggested by dose-dependent increases in the expression of CD11b (Figure 3E). These data support the potential of pharmacologic targeting of PRMT5 in AML as a novel antileukemic therapy. Reference: Leukemia. 2016 Apr; 30(4): 789–799. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034866/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 63.0 | 165.39 |
The following data is based on the product molecular weight 380.92 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Tarighat SS, Santhanam R, Frankhouser D, Radomska HS, Lai H, Anghelina M, Wang H, Huang X, Alinari L, Walker A, Caligiuri MA, Croce CM, Li L, Garzon R, Li C, Baiocchi RA, Marcucci G. The dual epigenetic role of PRMT5 in acute myeloid leukemia: gene activation and repression via histone arginine methylation. Leukemia. 2016 Apr;30(4):789-99. doi: 10.1038/leu.2015.308. Epub 2015 Nov 5. PMID: 26536822; PMCID: PMC8034866. |
| In vitro protocol: | 1. Tarighat SS, Santhanam R, Frankhouser D, Radomska HS, Lai H, Anghelina M, Wang H, Huang X, Alinari L, Walker A, Caligiuri MA, Croce CM, Li L, Garzon R, Li C, Baiocchi RA, Marcucci G. The dual epigenetic role of PRMT5 in acute myeloid leukemia: gene activation and repression via histone arginine methylation. Leukemia. 2016 Apr;30(4):789-99. doi: 10.1038/leu.2015.308. Epub 2015 Nov 5. PMID: 26536822; PMCID: PMC8034866. |
| In vivo protocol: | TBD |
1: Tarighat SS, Santhanam R, Frankhouser D, Radomska HS, Lai H, Anghelina M, Wang
H, Huang X, Alinari L, Walker A, Caligiuri MA, Croce CM, Li L, Garzon R, Li C,
Baiocchi RA, Marcucci G. The dual epigenetic role of PRMT5 in acute myeloid
leukemia: gene activation and repression via histone arginine methylation.
Leukemia. 2016 Apr;30(4):789-99. doi: 10.1038/leu.2015.308. Epub 2015 Nov 5.
PubMed PMID: 26536822.
