Elacridar (GF120918)

Catalog No.S7772 Batch:S777203

Print

Technical Data

Formula

C34H33N3O5
Molecular Weight 563.64 CAS No. 143664-11-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (177.41 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Elacridar (GF120918, GW120918, GG918, GW0918) is a potent P-gp (MDR-1) and BCRP inhibitor.
Targets
P-gp [1] BCRP [1]
In vitro Elacridar inhibits P-glycoprotein (P-gp) labeling by [3H]azidopine with a IC50 of 0.16 μM. [2] In Caki-1 and ACHN cells, elacridar ( 2.5 μM) significantly ihibits the cell growth. The P-glycoprotein activity is found to be inhibited by elacridar. The combination of elacridar and sunitinib lead to a significant reduction in ABC Sub-family B Member 2 (ABCG2) expression in 786-O cells. [3]
In vivo Oral co-administration of elacridar (100 mg/kg, p.o.) and crizotinib increases the plasma and brain concentrations and brain-to-plasma ratios of crizotinib in wild-type mice, equaling the levels in Abcb1a/1b; Abcg2-/- mice. [1] In friend leukemia virus stain B mice, the brain-to-plasm partition coefficient (Kp, brain) of elacridar is 0.82, 0.43, and 4.31 after intravenous (2.5 mg/kg), intraperitoneal (100 mg/kg), and oral (100 mg/kg) treatment, respectively. [4] In Mrp4(-/-) mice, elacridar fully inhibits P-gp mediated transport of topotecan, without siginificant effects on Bcrp1-mediated transport. [5]

Protocol (from reference)

Kinase Assay:[2]
  • Photoaffinity radiolabeling of P-gp

    10 μL of unlabeled cell membrane suspension (at 0.4 mg of protein/mL) are aliquoted into each well in 96-well plates. 5 μL of GF120918 are then added to each well. The plate is incubated 25 min at 25℃ in the dark. 5 μL of tritiated azidopine (1.8 TBq/mmol) (0.6 μM in HCI 0.2 mM) are added to each well. After 25 min of incubation at 25℃ in the dark, samples are simultaneously irradiated for 2 min at 254 nm at 0℃ with a thin layer chromatography-designed UV lamp directly in contact with the plate. Samples are solubilized in sodium dodecyl sulfate-polyacrylamide gel electrophoresis sample buffer but not heated. After separation on a 7.5% polyacrylamide gel, the gel is treated for fluorography with Amplify and exposed during 3 days onto a photosensitive film. The fluorography is analysed using a Camag thin layer chromatography Scanner II densitometer.
Cell Assay:[3]
  • Cell lines

    ACHN, Caki-1, 786-O, and MCF-7 cells

  • Concentrations

    ~ 5 mM

  • Incubation Time

    48 h

  • Method

    3.0×103 cells per well are seeded in a 96-well plate. After 24 h incubation, an optimum concentration gradient of elacridar is added to each well. After culturing for 48 h, cell viability is assessed using the proliferation reagent, MTT. Control cells are treated with the vehicle only, 0.1% DMSO. After this final incubation, the medium is aspirated and precipitated formazan crystals are dissolved in DMSO (100 μL/well). The absorbance of each well is measured at 540 nm, and a reference wavelength of 650 nm is read with a multiskan JX microplate reader. Cell viability is calculated as percentage of the control value.

Animal Study:[1]
  • Animal Models

    Male wild-type, Abcb1a/1b-/-34, Abcg2 -/-32 and Abcb1a/1b;Abcg2

  • Dosages

    100 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , J Exp Clin Cancer Res, 2017, 36(1):122]

Data from [Data independently produced by , , Biochem Pharmacol, 2016, 101:40-53.]

Data from [Data independently produced by , , Biochem Pharmacol, 2016, 101:40-53]

Selleck's Elacridar (GF120918) has been cited by 16 publications

Ritonavir reverses resistance to docetaxel and cabazitaxel in prostate cancer cells with acquired resistance to docetaxel [ Cancer Drug Resist, 2024, 7:3] PubMed: 38318527
Abcg2a is the functional homolog of human ABCG2 expressed at the zebrafish blood-brain barrier [ bioRxiv, 2023, 10.1101/2023.05.18.539313] PubMed: 37425689
Abcg2a is the functional homolog of human ABCG2 expressed at the zebrafish blood-brain barrier [ bioRxiv, 2023, 2023.05.18.539313] PubMed: 37425689
Activation of STAT3 through combined SRC and EGFR signaling drives resistance to a mitotic kinesin inhibitor in glioblastoma [ Cell Rep, 2022, 39(12):110991] PubMed: 35732128
Overcoming Resistance to Anti–Nectin-4 Antibody-Drug Conjugate [ Mol Cancer Ther, 2022, 21 (7): 1227–1235.] PubMed: None
Overcoming Resistance to Anti-nectin-4 Antibody-Drug Conjugate [ Mol Cancer Ther, 2022, molcanther.0013.2022] PubMed: 35534238
ETV7 regulates breast cancer stem-like cell features by repressing IFN-response genes [ Cell Death Dis, 2021, 12(8):742] PubMed: 34315857
Estradiol regulates intestinal ABCG2 to promote urate excretion via the PI3K/Akt pathway [ Nutr Metab (Lond), 2021, 18(1):63] PubMed: 34144706
Therapeutic Targeting of MDR1 Expression by RORγ Antagonists Resensitizes Cross-Resistant CRPC to Taxane via Coordinated Induction of Cell Death Programs. [ Mol Cancer Ther, 2020, 19(2):364-374] PubMed: 31712394
Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer. [ Nat Commun, 2019, 10(1):1295] PubMed: 30894541

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.