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Chemical Structure| 202592-23-2 Chemical Structure| 202592-23-2

Structure of JQ-1 (carboxylic acid)
CAS No.: 202592-23-2

Chemical Structure| 202592-23-2

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(+)-JQ1 carboxylic acid is a warhead ligand with a carboxylic acid functional group for conjugation reactions of PROTAC targeting on BET.

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Product Citations

Product Citations

Gotthardt, Gina ; Weckesser, Janik ; Tascher, Georg ; Barros da Gama, Sara ; Uckelmann, Hannah J ; Sun, Shibo , et al.

Abstract: Covalent inhibitors are an attractive targeting strategy that has expanded the development of degraders to target poorly druggable proteins including the E3 ligase RNF4. We show that RNF4 is a potential vulnerability of AML. High RNF4 expression levels correlate with poor patient survival and depletion of RNF4 results in increased sensitivity of AML cells to antileukemic drugs. Therefore, we aimed to develop chemical degraders (PROTACs) of RNF4 using a known covalent RNF4 ligand (CCW16), containing a chloro-N-acetamide group, as well as established E3 ligands targeting CRBN or VHL. However, while CCW16 and CCW16-derived PROTACs react potently with cysteines in recombinant RNF4, in cells, CCW16 forms covalent bonds with a large number of proteins, including peroxiredoxins. Consequently, CCW16 based PROTACs do not trigger degradation of RNF4, but induce the ferroptosis marker heme oxygenase-1 and impair cell viability in a distinct, RNF4-independent, ferroptotic cell death pathway. We hypothesize that other chloro-N-acetamide-containing E3 ligase ligands would also induce ferroptosis. Indeed, the RNF114 ligand EN219 also strongly induces ferroptosis, suggesting that ligands harboring this electrophile induce undesired off-target toxicity.

Keywords: AML ; CCW16 ; Covalent PROTACs ; Ferroptosis ; RNF4 Subject Categories Autophagy & Cell Death ; Post-translational Modifications & Proteolysis

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Product Details of JQ-1 (carboxylic acid)

CAS No. :202592-23-2
Formula : C19H17ClN4O2S
M.W : 400.88
SMILES Code : ClC1=CC=C(C(C2=C(N3C4=NN=C3C)SC(C)=C2C)=N[C@H]4CC(O)=O)C=C1
MDL No. :MFCD28167916
InChI Key :LJOSBOOJFIRCSO-AWEZNQCLSA-N
Pubchem ID :66828107

Safety of JQ-1 (carboxylic acid)

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of JQ-1 (carboxylic acid)

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
BCBL-1 50 nM 5 days To evaluate the synergistic anti-proliferative activity of JQ-1 in combination with lenalidomide Oncogene. 2016 Apr 7;35(14):1797-810
BC-3 50 nM 5 days To evaluate the synergistic anti-proliferative activity of JQ-1 in combination with lenalidomide Oncogene. 2016 Apr 7;35(14):1797-810
4T1 breast cancer cells 3.125 to 100 µM 1 to 3 days JQ-1 inhibited the growth of 4T1 cells by inducing apoptosis and autophagy, and reduced PD-L1 expression at low concentrations (≤1µM) Int J Mol Sci. 2024 Jan 4;25(1):663
A549 cells 5 µM 48 hours JQ-1 suppressed the viability of DPP-treated A549 cells pretreated with DSF and downregulated PD-L1 expression levels. Int J Mol Med. 2024 Feb;53(2):19
MR49F cells 500 nM 3 days JQ-1 suppressed DHT- or enzalutamide-induced growth of MR49F cells and attenuated AR target gene expression. Oncotarget. 2016 Jun 28;7(26):40690-40703
24ST1NLESG cells 1 μM 48 hours to screen for kinase inhibitors that block HIV-1 latency reversal Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01744-18

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD.SCID mice Orthotopic xenograft model Intraperitoneal injection 50 mg/kg Once daily for 28 days To evaluate the in vivo efficacy of lenalidomide in combination with JQ-1 Oncogene. 2016 Apr 7;35(14):1797-810
Balb/c mice 4T1 breast cancer model Intraperitoneal injection 50 mg/kg Three times per week until the end of the experiment JQ-1 alone or in combination with SZU-101 inhibited tumor growth and metastasis, reduced PD-L1 expression, and promoted the activation and recruitment of CD8+ T cells Int J Mol Sci. 2024 Jan 4;25(1):663
Nude mice MR49F xenograft model Intraperitoneal injection 50 mg/kg Monday-Friday for 4 weeks JQ-1 co-treatment with enzalutamide significantly suppressed MR49F xenograft growth. Oncotarget. 2016 Jun 28;7(26):40690-40703

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.49mL

0.50mL

0.25mL

12.47mL

2.49mL

1.25mL

24.95mL

4.99mL

2.49mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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