JQKD82 HCl | CAS#2410512-38-6 | KDM5 inhibitor

MedKoo Cat#: 408145 | Name: JQKD82 HCl

Description:

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

JQKD82, also known as PCK82, is a cell-permeable and selective KDM5 inhibitor (MM.1S cells, IC50 = 0.42 uM). JQKD82 increases histone H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output in vitro and in vivo. JQKD82 is a useful tool compound to block KDM5A function as a potential therapeutic strategy for MM. QKD82 is a more stable ester of KDM5-C49 that is able to deliver the active molecule KDM5-C49 to cells more efficiently

Chemical Structure

JQKD82 HCl

CAS#2863676-87-1 (3HCl)

Theoretical Analysis

MedKoo Cat#: 408145

Name: JQKD82 HCl

CAS#: 2863676-87-1 (3HCl)

Chemical Formula: C27H43Cl3N4O5

Exact Mass: 0.0000

Molecular Weight: 610.01

Elemental Analysis: C, 53.16; H, 7.11; Cl, 17.43; N, 9.18; O, 13.11

Price and Availability

Size	Price	Availability
1mg	USD 90.00	Ready to ship
5mg	USD 350.00	Ready to ship
10mg	USD 600.00	Ready to ship
25mg	USD 1,150.00	Ready to ship
50mg	USD 2,050.00	Ready to ship
100mg	USD 3,450.00	Ready to ship

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Related CAS #

2410512-38-6 (free base) 2863676-87-1 (3HCl)

Synonym

JQKD82 HCl; JQKD82 hydrochloride; JQKD82; JQKD-82; JQKD 82; PCK82; PCK-82; PCK 82;

IUPAC/Chemical Name

2,4-diisopropoxyphenyl 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinate trihydrochloride

InChi Key

VSTHCFWHQMJPDZ-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H40N4O5.3ClH/c1-8-31(14-13-30(6)7)26(32)18-28-17-22-15-21(11-12-29-22)27(33)36-24-10-9-23(34-19(2)3)16-25(24)35-20(4)5;;;/h9-12,15-16,19-20,28H,8,13-14,17-18H2,1-7H3;3*1H

SMILES Code

O=C(OC1=CC=C(OC(C)C)C=C1OC(C)C)C2=CC=NC(CNCC(N(CCN(C)C)CC)=O)=C2.[H]Cl.[H]Cl.[H]Cl

Appearance

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T22D06P17

QC Data

View QC data: current batch, Lot#T22D06P17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

KDM5 inhibitor (MM.1S cells, IC50 = 0.42 uM)

In vitro activity:

JQKD82 inhibited the growth of MM.1S cells in a dose and time-dependent manner (Supplementary Fig. S3A). JQKD82 was 7-fold more potent than KDM5-C70, and more than 20-fold more potent than KDM5-C49 at eliciting growth suppression in MM.1S cells (JQKD82 IC50 = 0.42 M, KDM5-C49 IC50 > 10 M, KDM5-C70 IC50 = 3.1 M) (Fig. 3A). Further, JQKD82 treatment resulted in suppressed growth in a panel of MM cell lines (Fig. 3B). These results were validated by treatment of five primary MM patient samples with JQKD82, which demonstrated a 40-50% reduction in cell viability after five days of treatment (Fig. 3C). As a control, we isolated normal B cells from healthy individuals, and treated these cells with JQKD82. CD40 antibody and IL-4-stimulated B cells were insensitive to the effects of JQKD82 (Fig. 3D), indicating that KDM5 inhibition may have a favorable in vivo therapeutic index. To further establish whether JQKD82 was effective at suppressing growth across multiple distinct lineages, we performed a screen of 367 distinct cancer cell lines, which were barcoded and pooled (39). JQKD82 was effective at reducing the growth of multiple tumor cell lineages, including MM cells, indicating potential cross-cancer utility (Supplementary Fig. S3B).

In vivo activity:

JQKD82 results in a dramatic reduction of MYC immunostaining in vivo (Fig 3K). In parallel to this, two groups of mice were treated with either JQKD82 or vehicle (n = 10 for each group) once tumor engraftment was confirmed by sequential BLI. As in our intravenous model, JQKD82 treatment for 14 days also significantly inhibited tumor growth, evidenced both by BLI and tumor size measurement (Supplementary Fig. S3H and S3I). These results indicate that JQKD82 is effective and well tolerated in vivo in two models of MM, and suggests a link between KDM5 function and MYC expression.

Preparing Stock Solutions

The following data is based on the product molecular weight 610.01 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. Ohguchi H, Park PMC, Wang T, Gryder BE, Ogiya D, Kurata K, Zhang X, Li D, Pei C, Masuda T, Johansson C, Wimalasena VK, Kim Y, Hino S, Usuki S, Kawano Y, Samur MK, Tai YT, Munshi NC, Matsuoka M, Ohtsuki S, Nakao M, Minami T, Lauberth S, Khan J, Oppermann U, Durbin AD, Anderson KC, Hideshima T, Qi J. Lysine Demethylase 5A is Required for MYC Driven Transcription in Multiple Myeloma. Blood Cancer Discov. 2021 Jul;2(4):370-387. doi: 10.1158/2643-3230.BCD-20-0108. Epub 2021 Apr 10. PMID: 34258103; PMCID: PMC8265280.

In vitro protocol:

In vivo protocol:

Lysine Demethylase 5A is Required for MYC Driven Transcription in Multiple Myeloma Hiroto Ohguchi1*#, Paul M.C. Park2*, Tingjian Wang2*, Berkley E. Gryder3,4*, Daisuke Ogiya5, Keiji Kurata5, Xiaofeng Zhang2, Deyao Li2, Chengkui Pei2, Takeshi Masuda6, Catrine Johansson7, Virangika K. Wimalasena2, Yong Kim3, Shinjiro Hino8, Shingo Usuki9, Yawara Kawano10, Mehmet K. Samur5, Yu-Tzu Tai5, Nikhil C. Munshi5, Masao Matsuoka10, Sumio Ohtsuki6, Mitsuyoshi Nakao8, Takashi Minami11, Shannon Lauberth12, Javed Khan3, Udo Oppermann7,13, Adam D. Durbin14, Kenneth C. Anderson5,15#, Teru Hideshima5#, Jun Qi2,15,16#