JQKD82 HCl

• CAS: 2410512-38-6
• Catalog Number: ACM2410512386
• Category: Inhibitors
• Molecular Weight: 610.01
• Molecular Formula: C27H43Cl3N4O5
• Description: 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
• Synonyms: JQKD82 HCl; JQKD82 hydrochloride; JQKD82; JQKD-82; JQKD 82; PCK82; PCK-82; PCK 82
• IUPAC Name: 2,4-diisopropoxyphenyl 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinate trihydrochloride
• Canonical SMILES: 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
• InChI: 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
• InChI Key: VSTHCFWHQMJPDZ-UHFFFAOYSA-N
• Solubility: To be determined
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: KDM5 inhibitor (MM.1S cells, IC50 = 0.42 uM)
• Drug Formulation: To be determined
• Elemental Analysis: C, 53.16; H, 7.11; Cl, 17.43; N, 9.18; O, 13.11
• Exact Mass: 500.2999
• HS Tariff Code: 2934.99.9001
• 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.
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).