2. Cell Cycle/DNA Damage Apoptosis Metabolic Enzyme/Protease Immunology/Inflammation NF-κB Autophagy
  3. Deubiquitinase Ferroptosis Reactive Oxygen Species (ROS) Glutathione Peroxidase Autophagy
  4. NCI677397

NCI677397 is a USP24 inhibitor. NCI677397 increases lipid ROS, activates cholesterol and fatty acid biosynthesis, degrades ABC transporters, GPX4 and DHFR through the autophagy pathway, decreases the level of P-gp and ultimately leads to ferroptosis in drug-resistant cancer cells. NCI677397 can be used for the study of lung caner and brain cancer.

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NCI677397 Chemical Structure

NCI677397 Chemical Structure

CAS No. : 907547-06-2

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NCI677397 Related Antibodies

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USP1 USP2 USP7 USP8 USP10 USP30 UCHL1

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Description

NCI677397 is a USP24 inhibitor. NCI677397 increases lipid ROS, activates cholesterol and fatty acid biosynthesis, degrades ABC transporters, GPX4 and DHFR through the autophagy pathway, decreases the level of P-gp and ultimately leads to ferroptosis in drug-resistant cancer cells. NCI677397 can be used for the study of lung caner and brain cancer[1][2].

In Vitro

NCI677397 (0-120 nM, 24 h-7 d) effectively reverses drug resistance in multiple cancer types: Lung cancer (T24 cells) resistant to Taxol, Brain cancer (Pt3-TMZR and U87-R cells) resistant to TMZ (HY-17364), Nasopharyngeal cancer (Hone-1-CPTR cells) resistant to CPT (HY-16560) and Colorectal cancer (HCT116-OXR cells) resistant to oxaliplatin (HY-17371)[2].
NCI677397 (10 and 20 μM, 4 days) significantly reduces the viability of TMZ-sensitive and -resistant GBM cells and there is a synergistic effect combined with TMZ[1].
NCI677397 (0-20 μM, 24 h) induces autophagy, not apoptosis in both TMZ-sensitive and TMZ-resistant GBM cells and A549 and Taxol-resistant A549 (A549-T24) cells[1].
NCI677397 (0-15 μM, 24 h) induces the biosynthesis of cholesterol and fatty acid in U87, U87R, Pt’3, Pt’3R, A549 and A549-T24 cells[1].
NCI677397 (0-25 μM, 24 h) induces ferroptosis mediated via lipid ROS in U87, U87R, Pt’3, Pt’3R and A549-T24 cells[1].
NCI677397 (0-25 μM, 24 h) degrades ABCG1/5/8 through the autophagy pathway and reduces the stability of GPX4 and DHFR in Pt’3R and A549-T24 cells[1].
NCI677397 (20 μM, 0-24 h) induces lipid peroxidation within 2 hours, upregulates cholesterol synthase 6 hours later, and completes the ferroptosis process 24 hours later in Pt’3R cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

NCI677397 Related Antibodies

Cell Viability Assay[1]

Cell Line: TMZ-sensitive GBM cells (Pt’3, A172 and U87 cells) and TMZ-resistant GBM cells (Pt’3R, A172R and U87R cells)
Concentration: 0, 10 and 20 μM
Incubation Time: 4 days
Result: Significantly decreased the viability combined with TMZ treatment.

Western Blot Analysis[1]

Cell Line: TMZ-sensitive GBM cells (Pt’3, A172 and U87 cells) and TMZ-resistant GBM cells (Pt’3R, A172R and U87R cells)
Concentration: 0, 5, 10, 15, 20 μM
Incubation Time: 24 h
Result: Increased the levels of autophagosome-associated lipidated form of LC3B (LC3B-II).
Did not increase the levels of Bax, an apoptotic marker.
Increasing autophagic and apoptotic cell death with TMZ.

Immunofluorescence[1]

Cell Line: Pt’3R cells
Concentration: 15 μM
Incubation Time: 24 h
Result: Induced accumulation of LC3B spots.

Western Blot Analysis[1]

Cell Line: Pt’3, Pt’3R and A549-T24cells
Concentration: 0, 5, 10, 15, 20, 25 μM
Incubation Time: 24 h
Result: Increased the levels of p-IRE1a, Bip, XBP1, p-eIF2a and CHOP in Pt’3 cells.
Increased the levels of ACSL3 and ACSL4 in brain and lung cancer cells.
Increased heme oxygenase-1 (HO-1) and p62/SQSTM1.
Induced SLC47A1 upregulation in both A549-T24 and Pt30R cells.
In Vivo

NCI677397Z (20 mg/kg, i.p., twice a week for 7 weeks) significantly inhibits tumor growth in U87R xenograft mice model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: U87R xenograft model established in male nonobese diabetic/severe combined immunodeficiency mice (8 weeks old)[1]
Dosage: 20 mg/kg
Administration: Intraperitoneal injection (i.p.), twice a week for 7 weeks
Result: led to smaller tumor size and lower tumor weight.
Molecular Weight

457.63

Formula

C28H31N3OS
CAS No.
SMILES

O=C(C1=CC=C2SC3=C(N(CCCCN4CCN(CC4)C)C2=C1)C=CC=C3)C5=CC=CC=C5
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Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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NCI677397 Related Classifications

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NCI677397907547-06-2NCI 677397NCI-677397DeubiquitinaseFerroptosisReactive Oxygen Species (ROS)Glutathione PeroxidaseAutophagyDUBsCancerLipid peroxidationSmall molecular inhibitorUSP24Inhibitorinhibitorinhibit

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