2. Cell Cycle/DNA Damage Epigenetics
  3. PARP
  4. PARP1-IN-40

PARP1-IN-40 is a highly selectively and orally active PARP1 inhibitor (IC50: 0.19 nM for PARP1, 26 nM for PARP2). PARP1-IN-40 kills tumor cells by inhibiting PARP1, leading to accumulation of DNA damage. PARP1-IN-40 has high antitumor activity against BRCA mutant MDA-MB-436 cells. PARP1-IN-40 can be used in combination with chemotherapy for cancer-related research.

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

PARP1-IN-40 Chemical Structure

PARP1-IN-40 Chemical Structure

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.

PARP1-IN-40 Related Antibodies

Top Publications Citing Use of Products

View All PARP Isoform Specific Products:

View All Isoforms
PARP PARP1 PARP2 PARP3 PARP4 TNKS1/PARP5A TNKS2/PARP5B PARP7 PARP10 PARP14 PARP15 PARP12 PARP16

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

PARP1-IN-40 is a highly selectively and orally active PARP1 inhibitor (IC50: 0.19 nM for PARP1, 26 nM for PARP2). PARP1-IN-40 kills tumor cells by inhibiting PARP1, leading to accumulation of DNA damage. PARP1-IN-40 has high antitumor activity against BRCA mutant MDA-MB-436 cells. PARP1-IN-40 can be used in combination with chemotherapy for cancer-related research[1].

In Vitro

PARP1-IN-40 (Compound (S)-G9) (1-100 nM, 3 days) blocks the MDA-MB-436 cell cycle at the G2/M phase and inhibits proliferation[1].

PARP1-IN-40 (0.1-1000 nM, 3 days) induces DNA damage and double-strand breaks in MDA-MB-436 cells[1].

PARP1-IN-40 (0.1-10000 nM, 1 h) was almost inactive in PARP1-KO cells in A549 cells (IC50 > 9.8 μM), proving that its action is completely dependent on PARP1 and its inhibitory activity on PARP2 is extremely weak, thus avoiding the toxicity risk of traditional PARPi[1].

PARP1-IN-40 (0.1-10000 nM, 1 h) efficiently captures PARP1-DNA complexes (EC50 = 1.9 nM), while capturing PARP2 requires a thousand-fold concentration, making it a PARP1 selective capture agent[1].

PARP1-IN-40 (0.1-20000 nM, 10 days) selectively kills BRCA mutant cells, confirming that its synthetic lethality mechanism depends on homologous recombination deficiency[1].

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

PARP1-IN-40 Related Antibodies

Cell Cycle Analysis[1]

Cell Line: MDA-MB-436 cells
Concentration: 1 nM, 10 nM, 100 nM
Incubation Time: 3 days
Result: Reduced the number of cells in S phase and significantly increased the number of cells in G2/M phase in a dose-dependent manner.

Cell Proliferation Assay[1]

Cell Line: MDA-MB-436 cells, DLD-1 BRCA2-KO cells, DLD-1 WT cells
Concentration: 0.1 nM, 1 nM, 10 nM, 100 nM (MDA-MB-436 cells, DLD-1 BRCA2-KO cells); 2.5 μM, 5 μM, 10 μM, 20 μM (DLD-1 WT cells)
Incubation Time: 10 days
Result: Completely inhibited clone formation in BRCA1 mutant (MDA-MB-436) and BRCA2 null (DLD-1 KO) cells at low concentrations, and showed no toxicity to BRCA wild-type cells (DLD-1 WT) even at high concentrations.

Immunofluorescence[1]

Cell Line: MDA-MB-436 cells
Concentration: 0.1 nM, 1 nM, 10 nM, 100 nM, 1000 nM
Incubation Time: 3 days
Result: Significantly increased the number of γH2AX foci.

Western Blot Analysis[1]

Cell Line: MDA-MB-436 cells
Concentration: 0.1 nM, 1 nM, 10 nM, 100 nM, 1000 nM
Incubation Time: 3 days
Result: Increased the expression of γH2AX.
In Vivo

PARP1-IN-40 (Compound (S)-G9) (0.3-3 mg/kg, p.o, for 27 days) potently inhibits the growth of BRCA mutant tumors without significant toxicity in the MDA-MB-231 xenograft mice model[1].

PARP1-IN-40 (1-3 mg/kg, p.o, for 14 days) has synergistic effect with chemotherapy in the HCT116 xenograft mice model[1].

PARP1-IN-40 (30-300 mg/kg, p.o, once dose; 30-100 mg/kg, p.o, for 14 days) is highly safe in the BALB/C nude mice[1].

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

Animal Model: MDA-MB-231 xenograft model established in nude mice[1]
Dosage: 0.3 mg/kg, 1 mg/kg, 3 mg/kg
Administration: Oral administration (p.o.), at the corresponding doses for 27 days
Result: Had TGI of 80 % at a dose of 0.3 mg/kg and 94 % at 3 mg/kg, with stable mouse body weight.
Blocked DNA repair in tumor tissues by selectively inhibiting PARP1, leading to the accumulation of γH2AX-mediated DNA damage, which in turn downregulated Ki67 to inhibit proliferation and drive anti-tumor efficacy.
Animal Model: HCT116 xenograft model established in nude mice[1]
Dosage: 1 mg/kg or 3mg/kg + liposomal Irinotecan (HY-16562) (2 mg/kg)
Administration: PARP1-IN-40: Oral administration (p.o.), at the corresponding doses for 14 days; liposomal Irinotecan: Intravenous injection (i.v.), twice weekly for 14 days.
Result: Had a TGI of 80 % at 1 mg/kg combined with chemotherapy and 85 % at 3 mg/kg.
Animal Model: Famale and male BALB/C nude mice[1]
Dosage: 30 mg/kg, 100 mg/kg, 300 mg/kg
Administration: Oral administration (p.o.) at 30 mg/kg and 100 mg/kg for 14 days; Oral administration (p.o.) at 30 mg/kg, 100 mg/kg and 300mg/kg once dose
Result: Did not cause death or significant weight changes in mice, and the histology of the heart, liver, spleen, lung, and kidney was normal.
Had no significant organ toxicity even at doses far higher than the therapeutic dose, and had excellent oral safety.
Molecular Weight

445.49

Formula

C25H24FN5O2
SMILES

CNC(C1=CC=C(C=N1)C2=CCN(C[C@H]2C)CC3=CC4=C(N5C=CC(F)=C5C(N4)=O)C=C3)=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.

PARP1-IN-40 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:

PARP1-IN-40PARPpoly ADP ribose polymeraseBRCAPARP1MDA-MB-436 cellsHCT116 cellsDLD-1 BRCA2-KO cellsA549 WT cellsInhibitorinhibitorinhibit

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:
PARP1-IN-40
Cat. No.:
HY-174442
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.