2. Cell Cycle/DNA Damage Apoptosis Metabolic Enzyme/Protease
  3. DNA/RNA Synthesis Apoptosis Cytochrome P450
  4. Polθ-IN-10

Polθ-IN-10 is an orally active Polθ-pol inhibitor (with a human IC50 of 1.3 nM) that exhibits oral bioavailability in mice and rats. Polθ-IN-10 binds to the allosteric site of Polθ-pol, disrupts the microhomology-mediated end-joining DNA repair pathway, and inhibits CYP2C9 (IC50=1.63 μM). Polθ-IN-10 selectively inhibits the proliferation of HR-deficient cancer cells and induces apoptosis. Polθ-IN-10 is applicable to the research of HR-deficient cancers.

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

Polθ-IN-10

Polθ-IN-10 Chemical Structure

CAS No. : 3068829-46-6

Size Stock
50 mg   Get quote  
100 mg   Get quote  
250 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Polθ-IN-10 Related Antibodies

Top Publications Citing Use of Products

View All DNA/RNA Synthesis Isoform Specific Products:

View All Isoforms
RNASE L DNA Polymerases RNA Polymerases Helicases DNA Ligase

View All Cytochrome P450 Isoform Specific Products:

View All Isoforms
CYP1 CYP2 CYP3 CYP4 CYP11 CYP17 Aromatase/CYP19A1 CYP26 CYP51 CYP1A2 CYP2D6 CYP2C9 CYP2C19 CYP3A CYP3A4 CYP17A1

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

Polθ-IN-10 is an orally active Polθ-pol inhibitor (with a human IC50 of 1.3 nM) that exhibits oral bioavailability in mice and rats. Polθ-IN-10 binds to the allosteric site of Polθ-pol, disrupts the microhomology-mediated end-joining DNA repair pathway, and inhibits CYP2C9 (IC50=1.63 μM). Polθ-IN-10 selectively inhibits the proliferation of HR-deficient cancer cells and induces apoptosis. Polθ-IN-10 is applicable to the research of HR-deficient cancers[1].

IC50 & Target

CYP2C9

1.63 μM (IC50)

In Vitro

Polθ-IN-10 (Compound 20) (10-60 min) potently and selectively inhibits the polymerase activity of human Polθ, with an IC50 of 1.3 nM, and does not inhibit other human DNA polymerases at a concentration of 10 μM[1].
Polθ-IN-10 (3-10 d) selectively inhibits the proliferation of HR-deficient cancer cell lines with an IC50 value ranging from 2.49 to 5.60 μM, while exerting minimal effects on HR-proficient cancer cell lines and normal cell lines[1].
Polθ-IN-10 (0-50.0 μM) preferentially inhibits CYP2C9 with an IC50 of 1.63 μM; it shows weak inhibitory activity against other CYP subtypes and exhibits no inhibitory effect on CYP1A2 even at concentrations as high as 50 μM[1].
Polθ-IN-10 (1.25-20 μM; 3-14 d) selectively and dose-dependently inhibits colony formation in HR-deficient MDA-MB-436 cells, while exerting no significant effect on normal MCF10A cells[1].
Polθ-IN-10 (5-20 μM; 7 d) dose-dependently induces apoptosis in HR-deficient MDA-MB-436 cells[1].
Polθ-IN-10 (1.25-10 μM; 2-48 h) induces time- and dose-dependent DNA damage in homologous recombination-deficient MDA-MB-436 cells[1].
Polθ-IN-10 (100 μM; 30 min) directly binds to Polθ protein in MDA-MB-436 cells and enhances its thermal stability[1].
Polθ-IN-10 (1 μM; 60 min) exhibits excellent metabolic stability in human, mouse and rat liver microsomes, with a half-life ranging from 121.6 to 247.5 min[1].
Polθ-IN-10 (30 μM; acute exposure) exhibits weak inhibitory activity against hERG channels, inducing only 24.0% inhibition at the concentration of 30 μM, which suggests that it possesses favorable cardiac safety profiles[1].

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

Polθ-IN-10 Related Antibodies

Cell Viability Assay[1]

Cell Line: HR-deficient cancer cell lines (MDA-MB-436, Capan-1, DLD-1 BRCA2-/-); HR-proficient/normal cell lines (DLD-1 BRCA2WT, MCF10A)
Concentration: Serial dilutions
Incubation Time: 7 days (MDA-MB-436, Capan-1); 10 days (DLD-1 BRCA2-/-); 3 days (MCF10A)
Result: Exhibited antiproliferative activity with IC50 values of 2.49 μM in MDA-MB-436 cells, 5.60 μM in Capan-1 cells, and 4.63 μM in DLD-1 BRCA2-/- cells.
Showed minimal activity with an IC50 >20 μM in DLD-1 BRCA2WT and MCF10A cells.

Apoptosis Analysis[1]

Cell Line: HR-deficient breast cancer cell line MDA-MB-436
Concentration: 5-20 μM
Incubation Time: 7 days
Result: Induced apoptosis in 24.7%, 33.1%, and 57.8% of MDA-MB-436 cells at concentrations of 5, 10, and 20 μM respectively, compared to the control group.

Western Blot Analysis[1]

Cell Line: HR-deficient breast cancer cell line MDA-MB-436
Concentration: 5 μM (time-dependent assay); 1.25-10 μM (dose-dependent assay)
Incubation Time: 2-12 h (time-dependent assay); 48 h (dose-dependent assay)
Result: Induced a time-dependent increase in γH2AX levels, with significant upregulation observed at 4 h and sustained through 12 h at 5 μM.
Also induced a dose-dependent increase in γH2AX levels, with significant upregulation at concentrations ≥2.5 μM after 48 h.
Parmacokinetics
Species Dose Route Cmax Tmax T1/2 MRT0-t MRT0-∞ AUC0-t AUC0-∞ F CL Vd
Mice[1] 2 mg/kg i.v. 2580 ng/mL / 2.22 h 2.03 h 2.37 h 4330 ng·h/mL 4470 ng·h/mL / 0.45 L/h/kg 1.06 L/kg
Mice[1] 10 mg/kg p.o. 7560 ng/mL 0.50 h 1.65 h 2.45 h 2.59 h 22800 ng·h/mL 23100 ng·h/mL 103.36 % / /
Rat[1] 3 mg/kg i.v. 949 ng/mL / 1.48 h 1.73 h 1.73 h 911 ng·h/mL 911 ng·h/mL / 3.51 L/h/kg 7.46 L/kg
Rat[1] 30 mg/kg p.o. 1361 ng/mL 1.00 h 4.34 h 4.02 h 4.86 h 5640 ng·h/mL 5803 ng·h/mL 63.71 % / /
In Vivo

Polθ-IN-10 (Compound 20) (25-100 mg/kg; p.o.; once daily; 28 days) significantly inhibits MDA-MB-436 xenograft tumor growth in a dose-dependent manner, achieving a maximum TGI of 61.14% at 100 mg/kg, with no evident in vivo toxicity[1].

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

Animal Model: NSG mice (female, 18-20 g, subcutaneous xenograft of MDA-MB-436 BRCA1 mutant human breast cancer cells)[1]
Dosage: 25 mg/kg; 50 mg/kg; 100 mg/kg
Administration: p.o.; once daily; 28 days
Result: Achieved tumor growth inhibition (TGI) rates of 45.49%, 51.99%, and 61.14% at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg, respectively.
Showed no significant mouse body weight loss across all treatment doses.
Detected a significant, dose-dependent increase in γH2AX (a DNA damage marker) expression in tumor tissue from treated mice.
Revealed no significant toxicity in histological analysis of heart, liver, spleen, lungs, and kidneys.
Molecular Weight

556.51

Formula

C27H24F4N6O3
CAS No.
SMILES

O=C(N(CC#CC1=NN=C(C=C1)C(O)(C)C)C2=CC=C(C=C2)F)[C@@H](N3C4=NC(C)=CC(C(F)(F)F)=C4)CNC3=O
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
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

Polθ-IN-10 Related Classifications

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2
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:

Polθ-IN-103068829-46-6DNA/RNA SynthesisApoptosisCytochrome P450CYPsHR-deficient cancer cellsHR-deficient cancersPolθ-polhuman PolθHR-deficient cancer cell linesnormal cell linesMCF10A cellsMDA-MB-436 cellsHR-proficient cell linesmicrohomology-mediated end joining DNA repair pathwayInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Requested Quantity *

Applicant Name *

 

Salutation

Email Address *

 

Phone Number *

Department

 

Organization Name *

City

State

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Polθ-IN-10
Cat. No.:
HY-181611
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

SAFETY DATA SHEET (SDS)

Request for HNMR Report

We have received your request and will respond to you as soon as possible.