2. MAPK/ERK Pathway Stem Cell/Wnt Autophagy Apoptosis PI3K/Akt/mTOR Metabolic Enzyme/Protease Immunology/Inflammation NF-κB
  3. ERK Autophagy Apoptosis p62 mTOR Reactive Oxygen Species (ROS) Ferroptosis
  4. SKLB-D18

SKLB-D18 is an orally active ERK1/2/ERK5 inhibitor, with an IC50 of 38.69 nM and a Kd of 126.9 nM against human ERK1, an IC50 of 40.12 nM and a Kd of 209.8 nM against ERK2, and an IC50 of 59.72 nM and a Kd of 468.2 nM against ERK5. SKLB-D18 inhibits cancer cell proliferation, induces G0/G1 cell cycle arrest and apoptosis. SKLB-D18 reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc, and upregulates the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in cells. SKLB-D18 increases LC3B-II accumulation, and decreases the levels of p62, p-mTOR and p-p70S6K. SKLB-D18 elevates the levels of ROS, lipid peroxidation and free ferrous ions, reduces the levels of NCOA4 and GPX4, and induces ferritin autophagy-dependent ferroptosis in cancer cells. SKLB-D18 exhibits antitumor activity in a triple-negative breast cancer xenograft mouse model. SKLB-D18 can be used in research related to triple-negative breast cancer.

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

SKLB-D18

SKLB-D18 Chemical Structure

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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10 mM * 1 mL in DMSO In-stock
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SKLB-D18 Related Antibodies

Top Publications Citing Use of Products

View All ERK Isoform Specific Products:

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ERK ERK1 ERK2 ERK5 ERK8

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mTOR mTORC1 mTORC2

  • Biological Activity

  • Purity & Documentation

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  • Customer Review

Description

SKLB-D18 is an orally active ERK1/2/ERK5 inhibitor, with an IC50 of 38.69 nM and a Kd of 126.9 nM against human ERK1, an IC50 of 40.12 nM and a Kd of 209.8 nM against ERK2, and an IC50 of 59.72 nM and a Kd of 468.2 nM against ERK5. SKLB-D18 inhibits cancer cell proliferation, induces G0/G1 cell cycle arrest and apoptosis. SKLB-D18 reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc, and upregulates the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in cells. SKLB-D18 increases LC3B-II accumulation, and decreases the levels of p62, p-mTOR and p-p70S6K. SKLB-D18 elevates the levels of ROS, lipid peroxidation and free ferrous ions, reduces the levels of NCOA4 and GPX4, and induces ferritin autophagy-dependent ferroptosis in cancer cells. SKLB-D18 exhibits antitumor activity in a triple-negative breast cancer xenograft mouse model. SKLB-D18 can be used in research related to triple-negative breast cancer[1].

IC50 & Target[1]

ERK1

38.69 nM (IC50)

ERK1

126.9 nM (Kd)

ERK2

40.12 nM (IC50)

ERK2

209.8 nM (Kd)

ERK5

59.72 nM (IC50)

ERK5

468.2 nM (Kd)

In Vitro

SKLB-D18 (1 μM) exhibits high selectivity for ERK1, ERK2 and ERK5, with inhibition rates of 96%, 94% and 83% respectively at the concentration of 1 μM[1].
SKLB-D18 (0-20 μM; 72 h) potently inhibits the proliferation of MDA-MB-231 (IC50 0.93 μM) and MDA-MB-468 (IC50 1.05 μM) in vitro, and this activity depends on the expression of ERK1/2/5[1].
SKLB-D18 (2 μM; 2 h) directly binds to ERK1/2 and ERK5 proteins in intact MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 24 h) reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc in a dose-dependent manner, while upregulating the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 14 days) potently and dose-dependently inhibits the long-term clonogenic proliferation of MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 24 h) induces dose-dependent G0/G1 cell cycle arrest in MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (0.5-2 μM; 16 h) potently and dose-dependently inhibits the migration of MDA-MB-231 and MDA-MB-468 cells[1].
SKLB-D18 (1-5 μM; 24 h) activates complete autophagic flux in MDA-MB-231 and MDA-MB-468 cells by inhibiting the mTOR/p70S6K pathway. After 24 h of treatment, increased accumulation of LC3B-II, and decreased levels of p62, p-mTOR and p-p70S6K are observed[1].
SKLB-D18 (1-5 μM; 24 h) induces ferritinophagy-dependent ferroptosis in MDA-MB-231 and MDA-MB-468 cells by increasing the levels of ROS, lipid peroxidation and free ferrous ions, and decreasing the levels of NCOA4 and GPX4[1].

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

SKLB-D18 Related Antibodies

Cell Viability Assay[1]

Cell Line: Triple-negative breast cancer (TNBC) cell lines MDA-MB-231, MDA-MB-468, MDA-MB-436, BT549; ERK1/2/5 knockdown MDA-MB-231 and MDA-MB-468 cells
Concentration: 0-20 μM
Incubation Time: 72 h
Result: Inhibited cell viability in a dose-dependent manner, with IC50 values of 0.93 μM (MDA-MB-231), 1.05 μM (MDA-MB-468), 2.31 μM (MDA-MB-436), and 3.21 μM (BT549).
Reduced anti-proliferative activity significantly in ERK1/2/5 knockdown MDA-MB-231 and MDA-MB-468 cells, with IC50 values of 14.81 μM and 19.84 μM, respectively.

Western Blot Analysis[1]

Cell Line: MDA-MB-231 and MDA-MB-468 TNBC cells
Concentration: 1-5 μM
Incubation Time: 24 h
Result: Reduced phosphorylated ERK5 (p-ERK5), phosphorylated RSKp90 (p-RSKp90), phosphorylated c-Myc (p-c-Myc), and total c-Myc levels in both cell lines in a dose-dependent manner.
Increased phosphorylated ERK1/2 (p-ERK1/2) levels in a dose-dependent manner, while total ERK1/2 and ERK5 levels remained unchanged.
Showed superior inhibition of p-ERK5, p-RSKp90, p-c-Myc, and c-Myc at 5 μM compared to a combination of BVD-523 and XMD8-92.

Cell Proliferation Assay[1]

Cell Line: MDA-MB-231 and MDA-MB-468 TNBC cells
Concentration: 1-5 μM
Incubation Time: 14 days
Result: Reduced colony formation in both cell lines in a dose-dependent manner.

Cell Cycle Analysis[1]

Cell Line: MDA-MB-231 and MDA-MB-468 TNBC cells
Concentration: 1-5 μM
Incubation Time: 24 h
Result: Induced G0/G1 phase cell cycle arrest in both MDA-MB-231 and MDA-MB-468 cells in a dose-dependent manner, with significant arrest observed at all tested concentrations.

Cell Migration Assay [1]

Cell Line: MDA-MB-231 and MDA-MB-468 TNBC cells
Concentration: 0.5-2 μM
Incubation Time: 16 h
Result: Reduced the number of migrated cells in both cell lines in a dose-dependent manner.

Cell Autophagy Assay[1]

Cell Line: MDA-MB-231 and MDA-MB-468 TNBC cells
Concentration: 1-5 μM (LC3/p62 immunoblotting); 5 μM (LC3 immunofluorescence, mTOR/p70S6K immunoblotting, autophagic flux assay with ±10 nM bafilomycin A1)
Incubation Time: 24 h
Result: Increased LC3B-II accumulation and reduced p62 levels in a dose-dependent manner.
Enhanced LC3 fluorescence intensity.
Induced complete autophagic flux, as confirmed by mRFP-GFP-LC3 assay with reduced green fluorescence when co-treated with bafilomycin A1.
Reduced phosphorylated mTOR (p-mTOR) and phosphorylated p70S6K (p-p70S6K) levels.
Parmacokinetics
Species Dose Route T1/2 Cmax AUC0-t AUC0-∞ Vss Vz CL Bioavailability
Rat[1] 10 mg/kg p.o. 3.71 h 53.71 ng/mL 303.93 ng·h/mL 456.92 ng·h/mL / / / 22.42 %
Rat[1] 1 mg/kg i.v. 2.01 h 58.72 ng/mL 135.56 ng·h/mL 143.25 ng·h/mL 16990.99 mL/kg 20240.48 mL/kg 116.52 mL/min/kg /
In Vivo

SKLB-D18 (25-50 mg/kg; p.o.; once daily; for 16 consecutive days) inhibits triple-negative breast cancer tumor growth in a dose-dependent manner in subcutaneous xenograft mouse models[1].

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

Animal Model: BALB/c-nu nude mice (female, 6 weeks old, 17-19 g, subcutaneous xenograft model)[1]
Dosage: 25 mg/kg; 50 mg/kg
Administration: p.o.; daily; 16 days
Result: Achieved a tumor inhibition rate of 59.23% relative to the control group at 25 mg/kg.
Achieved a tumor inhibition rate of 79.88% relative to the control group at 50 mg/kg, which was superior to the combination of BVD-523 and XMD8-92 (72.66% inhibition).
Caused a dose-dependent decrease in Ki-67-positive tumor cells, with less than 20% Ki-67-positive area in the 50 mg/kg group.
Induced a dose-dependent accumulation of p-ERK1/2 in tumor tissues, while dose-dependently inhibiting p-ERK5 expression, with stronger p-ERK5 inhibition at 50 mg/kg than the BVD-523 and XMD8-92 combination group.
Showed no significant body weight loss or major organ toxicity in either treatment group.
Molecular Weight

472.99

Formula

C22H25ClN6O2S
Appearance

Solid

Color

Off-white to light yellow

SMILES

CN(C)CC1=CC=CC(NC2=NC(C3=CSC(C(NN4CCOCC4)=O)=C3)=C(Cl)C=N2)=C1
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 : 35 mg/mL (74.00 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 2.1142 mL 10.5710 mL 21.1421 mL
5 mM 0.4228 mL 2.1142 mL 4.2284 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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In Vivo Dissolution Calculator
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Purity & Documentation
References

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 2.1142 mL 10.5710 mL 21.1421 mL 52.8552 mL
5 mM 0.4228 mL 2.1142 mL 4.2284 mL 10.5710 mL
10 mM 0.2114 mL 1.0571 mL 2.1142 mL 5.2855 mL
15 mM 0.1409 mL 0.7047 mL 1.4095 mL 3.5237 mL
20 mM 0.1057 mL 0.5286 mL 1.0571 mL 2.6428 mL
25 mM 0.0846 mL 0.4228 mL 0.8457 mL 2.1142 mL
30 mM 0.0705 mL 0.3524 mL 0.7047 mL 1.7618 mL
40 mM 0.0529 mL 0.2643 mL 0.5286 mL 1.3214 mL
50 mM 0.0423 mL 0.2114 mL 0.4228 mL 1.0571 mL
60 mM 0.0352 mL 0.1762 mL 0.3524 mL 0.8809 mL
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SKLB-D18 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:

SKLB-D18ERKAutophagyApoptosisp62mTORReactive Oxygen Species (ROS)FerroptosisExtracellular signal regulated kinasesSequestosome-1SQSTM1Mammalian target of RapamycinERK1/2/ERK5 inhibitortriple-negative breast cancerautophagyferroptosisapoptosisMDA-MB-231 cellsMDA-MB-468 cellsBALB/c-nu nude miceInhibitorinhibitorinhibit

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