PTC-209 HBr

Catalog No.S7539 Batch:S753901

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Technical Data

Formula

C17H13Br2N5OS.HBr
Molecular Weight 576.10 CAS No. 1217022-63-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (173.58 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.)

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Biological Activity

Description PTC-209 HBr is the hydrobromide salt of PTC-209, which is a potent and selective BMI-1 inhibitor with IC50 of 0.5 μM, and results in irreversible reduction of cancer-initiating cells (CICs).
Targets
BMI-1 [1]
0.5 μM
In vitro PTC-209 inhibits both the UTR-mediated reporter expression and endogenous BMI-1 expression in human colorectal HCT116 and human fibrosarcoma HT1080 tumor cells. PTC-209 decreases colorectal tumor cell growth in a BMI-1-dependent way. In addition, PTC-209 impairs colorectal cancer-initiating cells (CICs) through irreversible growth inhibition. [1]
In vivo PTC-209 (60 mg/kg/day, s.c.) effectively inhibits BMI-1 production in tumor tissue, and halts growth of preestablished tumors in mice bearing primary human colon cancer xenograft, human colon cancer cell lines LIM1215 or HCT116 xenografts. PTC-209 also reduces the frequency of functional colorectal CICs in vivo. [1]
Features BMI-1-selective inhibitor, targeting the BMI-1 self-renewal machinery.

Protocol (from reference)

Kinase Assay:[1]
  • Untranslated region-mediated luciferase reporter expression

    HEK293 cells are transfected with a GEMS reporter vector that contains the luciferase open-reading frame flanked by and under post-transcriptional control of the BMI-1 5′ and 3′ UTRs. The resulting stable cells (F8) are treated with PTC-209 or vehicle control overnight, and then luciferase reporter activity is determined using Bright-Glo assays. The assays are run in triplicate for each point, and the percentage of inhibition was calculated against vehicle control.
Cell Assay:[1]
  • Cell lines

    Human lymphoma U937 and HT1080 tumor cells, primary human peripheral blood mononuclear cells and human hematopoietic stem cells.

  • Concentrations

    ~10 μM

  • Incubation Time

    4 days

  • Method

    To determine whether pretreatment with the inhibitor affects tumor cell growth, cells are plated with the inhibitor for 4 d in vitro and plated in limiting doses in vitro without adding further inhibitor. Trypan blue exclusion is used to count viable cells. The in vitro sphere-initiating cell frequency is calculated after inhibitor treatment by evaluating the number of wells containing spheres. For the experiments where LDAs are set up following recovery of PTC-209 treated cells, 6-well plates were seeded with 1E6 cells per well and incubated overnight. Cells are subsequently treated for 4 d in triplicate with either DMSO vehicle or PTC-209 (0.01, 0.1, 1 and 10 μM). Drug treatments are washed off and 4 mL fresh suspension medium added to all wells. To assess cell viability following the 4 d treatment window, cells are trypsinized and counted at 0, 24, 72 and 120 h after removal of the drug. Long-lasting effects of the drug treatment on sphere-forming ability are assessed by plating LDAs (50,000, 10,000, 1,000,100, 10 and 1 cell per well) using the cells obtained 120 h after the 4-d drug treatment.
Animal Study:[1]
  • Animal Models

    Primary human colon cancer xenograft, human colon cancer cell lines LIM1215 and HCT116 xenografts in nude mice.

  • Dosages

    ~60 mg/kg/day

  • Administration

    s.c.

Customer Product Validation

Data from [Data independently produced by , , J Hematol Oncol, 2016, 9:17]

Data from [Data independently produced by , , Oncotarget, 2016, 7(1):745-58]

Data from [Data independently produced by , , Cell Cycle, 2018, 17(10):1199-1211]

Selleck's PTC-209 HBr has been cited by 15 publications

Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation [ Nat Commun, 2023, 10.1038/s41467-023-42930-y] PubMed: 37923799
BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling [ Int J Biol Sci, 2022, 18(7):2807-2820] PubMed: 35541907
PRC1-independent binding and activity of RYBP on the KSHV genome during de novo infection [ PLoS Pathog, 2022, 18(8):e1010801] PubMed: 36026503
BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1 [ Cancer Cell Int, 2022, 22(1):136] PubMed: 35346195
Identification of a novel binding inhibitor that blocks the interaction between hSCARB2 and VP1 of enterovirus 71 [ Cell Insight, 2022, 1(2):100016] PubMed: 37193133
BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway [ Front Cell Dev Biol, 2021, 9:665089] PubMed: 33928089
BMI1 promotes spermatogonia proliferation through epigenetic repression of Ptprm [ Biochem Biophys Res Commun, 2021, 583:169-177] PubMed: 34739857
Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells [ Exp Ther Med, 2021, 21(6):619] PubMed: 33936276
BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells [ Cell Cycle, 2020, 19(15):1884-1898] PubMed: 32594840
Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model [ Neural Plast, 2020, 2020:8823785] PubMed: 33082778

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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.

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