Cat. No.: HY-182241

JR4-187

JR4-187 is an orally active, copper-dependent anticancer agent. JR4-187 downregulates genes involved in oxidative phosphorylation, MYC targets and E2F targets in cancer cells, while upregulates genes involved in the TNF-α signaling pathway, p53 pathway and KRAS signaling pathway, and downregulates CTR1 protein. JR4-187 induces ROS production, apoptosis, copper-dependent cytotoxicity, and exhibits selective cytotoxicity against KRAS-mutant cancer cells. JR4-187 is well tolerated in mouse models of pancreatic cancer. JR4-187 can be used in research related to cancers such as pancreatic ductal adenocarcinoma, colon cancer and rectal cancer.

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CAS No.: 2446965-01-9
Formule: C₂₃H₂₅FN₆O₂
Masse moléculaire:436.48

Stockage:

Please store the product under the recommended conditions in the Certificate of Analysis.

JR4-187 Chemical Structure

CAS No.: 2446965-01-9

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Activité biologique
- Description
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Pureté et documentation
Références
Calculators
Help & FAQs
Classifications
Bioz

Activité biologique

Description

Voir tous les produits spécifiques à Isoform TNF Receptor :

Cellular Effect

Cell Line	Type	Value	Description	References
BXPC-3	IC₅₀	8.5 μM Compound: 39; JR4-187	Cytotoxicity against human BXPC-3 cells by MTT assay Cytotoxicity against human BXPC-3 cells by MTT assay	[PMID: 40135521]

In Vitro

JR4-187 (2 μM; 24 h) downregulates genes involved in oxidative phosphorylation, MYC targets and E2F targets in HCT116 cells, while upregulates genes involved in the TNF-α signaling pathway, p53 pathway and KRAS signaling pathway^[1].
JR4-187 (2.5-15 μM; 4-24 h) significantly downregulates the expression of MYC and NDUFS7 proteins in HCT116, MIA PaCa-2, PANC1 and BXPC3 cells^[1].
JR4-187 (0.03-1 μM; 6 days) exerts synergistic cytotoxic effects in HCT116 colon cancer cells when combined with specific compounds (Danazol (HY-B1029), Metformin (HY-B0627), IACS-010759 (HY-112037), Rotenone (HY-B1756), DX2-201 (HY-145303), DX3-213B (HY-144310), AGB-374 (HY-182242)), and antagonistic effects when combined with MYCi361 (HY-129600), 10058-F4 (HY-12702), MYCMI-6 (HY-124675)^[1].
JR4-187 (10 μM; 24 h) significantly downregulates the expression of CTR1 protein in HCT116 and MIA PaCa-2 cells^[1].
Combination treatment with JR4-187 (2.5 μM; 24 h) and 5 μM AGB-374 synergistically downregulates the protein expression of MYC and NDUFS7 in HCT116 colon cancer cells^[1].
JR4-187 (Compound 39) potently inhibits the proliferation of KRAS-mutant pancreatic and colon cancer cells, with the highest activity observed in SU.86.86 cells (IC₅₀ = 0.8 μM) and MIA PaCa-2 cells (IC₅₀ = 1.9 μM), and lower activity in KRAS wild-type BxPC-3 cells^[2].
JR4-187 (0-10 μM; 6 days) exerts copper-dependent cytotoxicity, exhibits strong synergy with CuSO₄ in MIA PaCa-2 and HCT116 cells, and shows reduced activity in the presence of the copper chelator TTM (HY-128530)^[2].
JR4-187 (0-5 μM; 6 days) exhibits strong synergistic effects with the COX2 inhibitors Celecoxib (HY-14398) and Rofecoxib (HY-17372) in inhibiting colony formation of HCT116, MIA PaCa-2 and BxPC-3 cells^[2].
JR4-187 (0-1 μM; 6 days) induces ROS-dependent cell death in HCT116 and MIA PaCa-2 cells^[2].
JR4-187 (0-10 μM; 1-6 days) partially induces cell death in MIA PaCa-2 and HCT116 cells via apoptosis and necroptosis^[2].

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

Western Blot Analysis^[1]

Cell Line:

HCT116 human colon cancer cells
Concentration:

10 μM
Incubation Time:

4 h; 24 h
Result:

Significantly downregulated MYC protein levels relative to control cells.

Western Blot Analysis^[1]

Cell Line:

MIA PaCa-2 and BXPC3 human pancreatic cancer cells
Concentration:

10 μM
Incubation Time:

24 h
Result:

Decreased MYC protein abundance in both MIA PaCa-2 and BXPC3 cells.

Western Blot Analysis^[1]

Cell Line:

HCT116 human colon cancer cells, MIA PaCa-2 and PANC1 human pancreatic cancer cells
Concentration:

2.5, 5, 7.5, 10, 15 μM
Incubation Time:

24 h
Result:

Caused a dose-dependent reduction in MYC protein levels in HCT116, MIA PaCa-2, and PANC1 cells.\nCaused a dose-dependent reduction in NDUFS7 protein levels in HCT116, MIA PaCa-2, and PANC1 cells.

Cell Cytotoxicity Assay^[1]

Cell Line:

HCT116 human colon cancer cells
Concentration:

0.03, 0.1, 0.3, 1 μM
Incubation Time:

6 days
Result:

Showed strong cytotoxic synergy with Danazol.
Showed strong antagonism with MYCi361, 10058-F4, and MYCMI-6.
Showed no significant interaction with 10074-G5.
Showed significant synergy with metformin, IACS-010759, and Rotenone.
Showed weak synergy with 2-DG.
Showed significant synergy with DX2-201, DX3-213B, and AGB-374.

Western Blot Analysis^[1]

Cell Line:

HCT116 human colon cancer cells and MIA PaCa-2 human pancreatic cancer cells
Concentration:

10 μM
Incubation Time:

24 h
Result:

Caused a marked decrease in CTR1 protein levels in both HCT116 and MIA PaCa-2 cells, with a log₁₀ fold change of ~-0.3 in HCT116 cells and ~-0.15 in MIA PaCa-2 cells.

Western Blot Analysis^[1]

Cell Line:

HCT116 human colon cancer cells
Concentration:

2.5 μM (alone and in combination with 5 μM AGB-374)
Incubation Time:

24 h
Result:

Led to synergistic downregulation of both MYC and NDUFS7 protein levels in HCT116 cells, compared to monotherapy with either agent.

Cell Cytotoxicity Assay^[2]

Cell Line:

MIA PaCa-2, HCT116
Concentration:

0, 0.018, 0.05, 0.16, 0.5 μM/0, 0.03, 0.1, 0.3, 1 μM/0. 0.3. 1.1, 3.3, 10 μM
Incubation Time:

6 days
Result:

Showed strong synergy with copper sulfate (CuSO₄) in both cell lines, as measured by the HSA model in Combenefit software.
Exhibited significantly reduced cytotoxic activity when combined with copper chelator ammonium Tetrathiomolybdate (TTM).

Cell Proliferation Assay^[2]

Cell Line:

HCT116, MIA PaCa-2, BxPC-3
Concentration:

0, 0.03, 0.1, 0.3, 1 μM (HCT116 with Celecoxib); 0, 0.018, 0.05, 0.16, 0.5 μM (MIA PaCa-2 with Celecoxib; MIA PaCa-2 with Rotecoxib); 0, 0.03, 0.1, 0.3, 1 μM (HCT116 with Rotecoxib); 0, 0.18, 0.5, 1.6, 5 μM ( BxPC-3 with Celecoxib)
Incubation Time:

6 days
Result:

Showed strong synergy with celecoxib across all three cell lines, as measured by the HSA model in Combenefit software.
Exhibited strong synergy with rotecoxib in HCT116 and MIA PaCa-2 cells, as measured by the HSA model in Combenefit software.

Cell Cytotoxicity Assay^[2]

Cell Line:

HCT116, MIA PaCa-2
Concentration:

0, 0.03, 0.1, 0.3, 1 μM (HCT116); 0, 0.018, 0.05, 0.16, 0.5 μM (MIA PaCa-2)
Incubation Time:

6 days
Result:

Induced cell death that was rescued by pretreatment with ROS scavenger N-acetyl cysteine (NAC) in both cell lines.

Cell Cytotoxicity Assay^[2]

Cell Line:

MIA PaCa-2, HCT116
Concentration:

0, 0.018, 0.05, 0.16, 0.5 μM (MIA PaCa-2 with Z-VAD-FMK; MIA PaCa-2 with Necrostatin-1); 0, 0.03, 0.1, 0.3, 1 μM (HCT116 with Z-VAD-FMK); 0, 0.07, 0.2, 0.6, 2 μM (HCT116 with necrostatin-1); 10 μM (WB for apoptosis markers); 10 μM (WB for necroptosis markers)
Incubation Time:

6 days/48 h (WB for apoptosis markers); 48 h (WB for necroptosis markers)
Result:

Induced cell death that was partially rescued by apoptosis inhibitor Z-VAD-FMK and necroptosis inhibitor necrostatin-1 in both cell lines.
Increased cleaved PARP, cleaved caspase-9, cleaved caspase-3 (apoptosis markers) in cells treated for 48 h, as confirmed by Western blot analysis.
Increased phospho-RIP3 (necroptosis marker) in cells treated for 1 h, as confirmed by Western blot analysis.

Parmacokinetics

Species	Dose	Route	C₀	AUC_0-last	AUC_0-inf	T_1/2	CL	V_ss	C_max	Bioavailability
Mice^[2]	15 mg/kg	i.v.	3458 ng/mL	6014 ng·h/mL	6087 ng·h/mL	2.8 h	37.7 mL/min/kg	7.1 L/kg	/	/
Mice^[2]	30 mg/kg	p.o.	/	6639 ng·h/mL	6801 ng·h/mL	4.9 h	/	/	1017 ng/mL	55.2 %

In Vivo

JR4-187 (20-40 mg/kg; i.p.; daily; days 1-28) is well tolerated in female C57BL/6 mice bearing PAN02 pancreatic cancer syngeneic allografts^[2].

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

Animal Model:

C57BL/6 (female)^[2]
Dosage:

40 mg/kg (days 1-20); 20 mg/kg (days 21-28)
Administration:

i.p.; daily; days 1-28
Result:

Showed no significant loss in body weight.

Chemical Information

CAS No. 2446965-01-9
Masse moléculaire 436.48
Formule C₂₃H₂₅FN₆O₂
SMILES

O=C(NC1=C2N=CC=CC2=CC(F)=C1)C3=CN=C(N(CC4)CCC4([C@@H]5N)CO[C@H]5C)C=N3
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage

Please store the product under the recommended conditions in the Certificate of Analysis.

Pureté et documentation

Instruction de manipulation (2659 KB)

Références

[1]. Rima Mouawad, et al. Copper Transporter 1-Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.

[2]. Roy J, et al. Copper-KRAS-COX2 Axis: A Therapeutic Vulnerability in Pancreatic Cancer. J Med Chem. 2025;68(8):8400-8428. [Content Brief]

Calculators

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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JR4-187

Voir tous les produits spécifiques à Isoform TNF Receptor

Activité biologique

Chemical Information

Pureté et documentation

Références

Calculators

Help & FAQs

JR4-187 Related Classifications

HY-182241 Related Classifications