2. Apoptosis Metabolic Enzyme/Protease
  3. Cuproptosis Mitochondrial Metabolism
  4. UM4118

UM4118 is a potent copper-selective non-genotoxic copper ionophore that induces cuproptosis in acute myeloid leukemia cells. UM4118 exhibits stronger activity against SF3B1G12C mutant acute myeloid leukemia cells. UM4118 transports extracellular copper into cells, elevates intracellular and mitochondrial copper levels, and triggers lipoylated DLAT aggregation, proteotoxic stress, iron-sulfur cluster protein depletion, reduced lipoylated protein levels, and maximal mitochondrial respiratory damage. UM4118 cytotoxicity can be enhanced by supplementation with extracellular copper, abolished by copper chelation, and shows synthetic lethal effects in the absence of iron-sulfur cluster biosynthesis/transport genes. UM4118 can be used for the study of acute myeloid leukemia.

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UM4118

UM4118 Chemical Structure

CAS No. : 324530-92-9

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10 mM * 1 mL in DMSO
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Based on 1 publication(s) in Google Scholar

UM4118 Related Antibodies

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Description

UM4118 is a potent copper-selective non-genotoxic copper ionophore that induces cuproptosis in acute myeloid leukemia cells. UM4118 exhibits stronger activity against SF3B1G12C mutant acute myeloid leukemia cells. UM4118 transports extracellular copper into cells, elevates intracellular and mitochondrial copper levels, and triggers lipoylated DLAT aggregation, proteotoxic stress, iron-sulfur cluster protein depletion, reduced lipoylated protein levels, and maximal mitochondrial respiratory damage. UM4118 cytotoxicity can be enhanced by supplementation with extracellular copper, abolished by copper chelation, and shows synthetic lethal effects in the absence of iron-sulfur cluster biosynthesis/transport genes. UM4118 can be used for the study of acute myeloid leukemia[1].

In Vitro

UM4118 (40 μM) binds copper and zinc in a cell-free system[1].
UM4118 (2 μM; 3 h) specifically increases intracellular copper levels in OCI-AML5 cells by importing copper from the extracellular media[1].
UM4118 (40 nM) shows potent and selective antiproliferative activity against OCI‑AML5 cells (IC50 = 40 nM) and is further potentiated in ABCB7‑downregulated OCI‑AML5 cells[1].
UM4118 (150 nM; 24 h) impairs maximal mitochondrial respiration capacity in OCI-AML5 cells, indicating reliance on mitochondrial respiration for its activity[1].
UM4118 (300 nM; 16 h) induces DLAT aggregation in OCI-AML5 cells, a hallmark of cuproptosis, with enhanced aggregation observed upon copper supplementation[1].
UM4118 (2 μM; 3 h) increases intramitochondrial copper levels in human embryonic kidney 293 cells[1].
UM4118 (110 nM; 14 day) has synthetic lethal interactions with knockdown of glycolysis enzymes, ISC biosynthesis genes, or ABCB7 in EKO OCI-AML5 cells, while knockdown of TCA cycle or lipoylation enzymes rescues cells from UM4118-induced cytotoxicity[1].
UM4118 acts synergistically with Pladienolide B (HY-16399) in OCI-AML5 cells[1].
UM4118 (20 nM; 48 h) reduces clonogenic potential of K562 cells, with a significantly stronger effect in SF3B1K700E mutant cells than in SF3B1 WT cells[1].

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

UM4118 Related Antibodies

Immunofluorescence[1]

Cell Line: OCI-AML5 acute myeloid leukemia cells
Concentration: 300 nM; 1 μM (copper supplement)
Incubation Time: 16 h
Result: Induced DLAT aggregation, with total DLAT fluorescence intensity increasing to ~1.2 (normalized to cell number) without copper and ~2.4 with copper, versus ~0.6 and ~0.8 in DMSO controls, respectively.
Had its induced DLAT aggregation further exacerbated by copper supplementation.

Cell Proliferation Assay[1]

Cell Line: isogenic K562 acute myeloid leukemia cells (SF3B1 WT vs. SF3B1 K700E mutant)
Concentration: 20 nM
Incubation Time: 48 h
Result: Reduced colony formation by a fold change of 28.1 in SF3B1 WT K562 cells and 98 in SF3B1 K700E mutant K562 cells.
Molecular Weight

249.27

Formula

C15H11N3O
CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

O=C(C1=NC=CC=C1)NC2=CC=CC3=CC=CN=C32
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 116.67 mg/mL (468.05 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 4.0117 mL 20.0586 mL 40.1171 mL
5 mM 0.8023 mL 4.0117 mL 8.0234 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
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Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 4.0117 mL 20.0586 mL 40.1171 mL 100.2929 mL
5 mM 0.8023 mL 4.0117 mL 8.0234 mL 20.0586 mL
10 mM 0.4012 mL 2.0059 mL 4.0117 mL 10.0293 mL
15 mM 0.2674 mL 1.3372 mL 2.6745 mL 6.6862 mL
20 mM 0.2006 mL 1.0029 mL 2.0059 mL 5.0146 mL
25 mM 0.1605 mL 0.8023 mL 1.6047 mL 4.0117 mL
30 mM 0.1337 mL 0.6686 mL 1.3372 mL 3.3431 mL
40 mM 0.1003 mL 0.5015 mL 1.0029 mL 2.5073 mL
50 mM 0.0802 mL 0.4012 mL 0.8023 mL 2.0059 mL
60 mM 0.0669 mL 0.3343 mL 0.6686 mL 1.6715 mL
80 mM 0.0501 mL 0.2507 mL 0.5015 mL 1.2537 mL
100 mM 0.0401 mL 0.2006 mL 0.4012 mL 1.0029 mL
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UM4118 Related Classifications

Help & FAQs
  • 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:

UM4118324530-92-9UM 4118UM-4118CuproptosisMitochondrial MetabolismcuproptosisSF3B1-mutated acute myeloid leukemia cellsAML cellsK562 cellshuman embryonic kidney 293 cellsDLATOCI-AML5 cellsacute myeloid leukemiairon-sulfur clustermitochondrial respirationInhibitorinhibitorinhibit

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