HLCL-61 HCl | CAS#1158279-20-9 | CAS#586395-74-6 | PRMT5 inhibitor

MedKoo Cat#: 406748 | Name: HLCL-61 HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

HLCL-61 HCl

CAS#1158279-20-9 (HCl)

Theoretical Analysis

MedKoo Cat#: 406748

Name: HLCL-61 HCl

CAS#: 1158279-20-9 (HCl)

Chemical Formula: C23H25ClN2O

Exact Mass: 344.1889

Molecular Weight: 380.92

Elemental Analysis: C, 72.52; H, 6.62; Cl, 9.31; N, 7.35; O, 4.20

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 650.00	Ready to ship
500mg	USD 1,450.00	Ready to ship
1g	USD 2,450.00	Ready to ship
2g	USD 4,450.00	2 weeks

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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)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC61104

QC Data

View QC data: current batch, Lot#BBC61104

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	63.0	165.39

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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.