2. Apoptosis Cell Cycle/DNA Damage Metabolic Enzyme/Protease Immunology/Inflammation NF-κB
  3. c-Myc Early 2 Factor (E2F) TNF Receptor MDM-2/p53 Reactive Oxygen Species (ROS) Apoptosis
  4. 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.

For research use only. We do not sell to patients.

JR4-187

JR4-187 Chemical Structure

CAS No. : 2446965-01-9

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JR4-187 Related Antibodies

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TNFRSF1A/CD120a TNFRSF3/CD18 TNFRSF4 TNFRSF5/CD40 TNFRSF6/Fas/CD95 TNFRSF7/CD27 TNFRSF8/CD30 TNFRSF9/4-1BB/CD137 TNFRSF10B/DR5/CD262 TNFRSF12A/TWEAK TNFRSF16/NGF Receptor/CD271 TNFRSF18/GITR/CD357

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Description

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[1][2].

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.

JR4-187 Related Antibodies

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 AUC0-last AUC0-inf T1/2 CL Vss Cmax 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.
Molecular Weight

436.48

Formula

C23H25FN6O2
CAS No.
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
Shipping

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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JR4-187 Related Classifications

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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:

JR4-1872446965-01-9c-MycEarly 2 Factor (E2F)TNF ReceptorMDM-2/p53Reactive Oxygen Species (ROS)ApoptosisMycTumor Necrosis Factor ReceptorTNFRCD-1 miceanticancer agentHCT116 cellsPDAC syngeneic mouse modelsKRAS-mutant cancer cellsPDAC allograft mouse modelspancreatic ductal adenocarcinomacolon cancer and rectal cancerC57BL/6miceInhibitorinhibitorinhibit

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