Cat. No.: HY-189005

PARP1-IN-60

PARP1-IN-60 is an orally active PARP1 inhibitor with a human IC₅₀ of 2.4 nM. PARP1-IN-60 selectively inhibits PARP1-mediated poly (ADP-ribosylation) (PARylation) compared with PARP2. PARP1-IN-60 induces DNA damage, G2/M phase arrest and antiproliferative activity in BRCA-deficient cells. PARP1-IN-60 can be used in the research of BRCA-mutant cancers and colorectal cancer.

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

Formula: C₂₅H₂₅FN₄O₃
Molecular Weight:448.49

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

PARP1-IN-60 Chemical Structure

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Protocols (5)
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]

PARP1

2.4 nM (IC₅₀)

All PARP Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC50	2.35 nM	Inhibition of poly(ADP-ribosyl)ation (PARylation) in A549 wild-type cells treated with PARP1-IN-60, exposed to 10 mM H₂O₂ for 5 min to induce DNA damage, followed by a 1 h incubation. Inhibition of poly(ADP-ribosyl)ation (PARylation) in A549 wild-type cells treated with PARP1-IN-60, exposed to 10 mM H₂O₂ for 5 min to induce DNA damage, followed by a 1 h incubation.	42593943
MDA-MB-436	IC50	0.2 nM	Antiproliferative activity against BRCA-mutant MDA-MB-436 cells. Antiproliferative activity against BRCA-mutant MDA-MB-436 cells.	42593943
SUM149PT	IC50	2.82 nM	Antiproliferative activity against BRCA-mutant SUM149PT cells. Antiproliferative activity against BRCA-mutant SUM149PT cells.	42593943
CAPAN-1	IC50	832 nM	Antiproliferative activity against BRCA-wild-type CAPAN-1 cells. Antiproliferative activity against BRCA-wild-type CAPAN-1 cells.	42593943
MDA-MB-231	IC50	197 nM	Antiproliferative activity against BRCA-wild-type MDA-MB-231 cells. Antiproliferative activity against BRCA-wild-type MDA-MB-231 cells.	42593943
Vero	IC50	1845 nM	Antiproliferative activity against normal VERO cells. Antiproliferative activity against normal VERO cells.	42593943
H9c2	IC50	2647 nM	Antiproliferative activity against normal H9C2 cells. Antiproliferative activity against normal H9C2 cells.	42593943

In Vitro

PARP1-IN-60 ((R)-A17) potently inhibits PARP1 with an IC₅₀ of 2.4 nM, and exhibits 65.8-fold selectivity for PARP2 over PARP1 in enzymatic assays^[1].
PARP1-IN-60 exhibits high selectivity for PARP1, with extremely low inhibitory activity against PARP3, PARP5A, PARP5B, PARP6, PARP7, PARP12, PARP14 and PARP15^[1].
PARP1-IN-60 (1 h) selectively inhibits PARP1-mediated PARylation, with an IC₅₀ of 2.35 nM in A549 wild-type cells, an IC₅₀ of 1.22 nM in A549 PARP2-knockout cells, and no significant activity in A549 PARP1-knockout cells^[1].
PARP1-IN-60 exhibits excellent metabolic stability in human liver microsomes, with a half-life of over 120 min and an intrinsic clearance of <12 mL/min/g protein^[1].
PARP1-IN-60 (0.1-100 nM; 10 days) inhibits colony formation in a dose-dependent manner in BRCA-deficient MDA-MB-436 cells and DLD-1 BRCA2 knockout cells, but exerts no such effect on BRCA-proficient DLD-1 wild-type cells^[1].
PARP1-IN-60 selectively inhibits the proliferation of BRCA-deficient MDA-MB-436 and SUM149PT cells, with IC₅₀ values of 0.2 nM and 2.82 nM, respectively, while exhibits much weaker activity against BRCA wild-type cells and normal cells^[1].
PARP1-IN-60 (0.1-1000 nM; 72 h) induces dose-dependent DNA damage in MDA-MB-436 cells, which is evidenced by increased γ-H2AX foci and elevated protein expression^[1].
PARP1-IN-60 (1-100 nM; 72 h) induces dose-dependent G₂/M phase arrest in MDA-MB-436 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.

Cell Proliferation Assay^[1]

View Protocol

Cell Line:

MDA-MB-436 (BRCA-deficient), DLD-1 wild-type, DLD-1 BRCA2-knockout
Concentration:

0.1-100 nM
Incubation Time:

10 days
Result:

Significantly suppressed colony formation in a dose-dependent manner in MDA-MB-436 and DLD-1 BRCA2-knockout cells.
Left DLD-1 wild-type cells largely unaffected even at 10 μM.

Cell Cycle Analysis^[1]

View Protocol

Cell Line:

MDA-MB-436
Concentration:

1-100 nM
Incubation Time:

72 h
Result:

Induced a dose-dependent decrease in S-phase cells.
Caused a corresponding accumulation of cells in G2/M phase.

Parmacokinetics

Species	Dose	Route	C_max	T_max	T_1/2	V_z	CL	AUC_0-t	F
Mice^[1]	1 mg/kg	i.v.	1342.55 μg/L	0.12 h	3.28 h	0.86 L/kg	0.18 L/h/kg	5500.51 μg/L·h	100 %
Mice^[1]	1 mg/kg	p.o.	962.65 μg/L	1.00 h	3.18 h	0.79 L/kg	0.17 L/h/kg	5681.56 μg/L·h	/

In Vivo

PARP1-IN-60 ((R)-A17) (0.3-3 mg/kg; p.o.; every other day) produces dose-dependent, well-tolerated antitumor efficacy in MDA-MB-436 xenograft mice, achieving a maximum tumor growth inhibition of 91.3% at 3 mg/kg^[1].
PARP1-IN-60 (1-3 mg/kg; p.o.; once daily) synergizes with liposomal irinotecan (Irinotecan liposome) (HY-185371) to produce dose-dependent enhanced antitumor efficacy in HCT116 xenograft mice, achieving a maximum tumor growth inhibition of 86.6% at 3 mg/kg combined with liposomal irinotecan^[1].
PARP1-IN-60 (30-300 mg/kg; p.o.; once daily; 14 days) is well-tolerated in healthy Balb/c mice with no observed adverse effects on body weight, blood counts, or serum chemistry^[1].
PARP1-IN-60 (500-1000 mg/kg; p.o.; single dose) is well-tolerated in healthy Balb/c mice with no observed mortality or adverse body weight effects^[1].

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

Animal Model:

NOD/SCID (female, 4-6 weeks old, 18-20 g, subcutaneous breast cancer xenograft model)^[1]
Dosage:

0.3 mg/kg; 1 mg/kg; 3 mg/kg
Administration:

p.o.; every other day
Result:

Achieved tumor growth inhibition (TGI) values of 57.8%, 86.3%, and 91.3% at doses of 0.3, 1, and 3 mg/kg, respectively.
Markedly reduced Ki67-positive tumor cell rate.
Caused no significant body weight loss across all doses.
Showed no apparent pathological abnormalities in major organs (heart, liver, spleen, lung, kidney) via hematoxylin and eosin (H&E) staining.

Animal Model:

Nu/Nu (female, 4-6 weeks old, subcutaneous colorectal cancer xenograft model)^[1]
Dosage:

1 mg/kg; 3 mg/kg (in combination with liposomal irinotecan 2 mg/kg)
Administration:

p.o.; once daily; liposomal irinotecan: i.v.; twice weekly
Result:

Achieved tumor growth inhibition (TGI) values of 77.2% at 1 mg/kg and 86.6% at 3 mg/kg when combined with liposomal irinotecan.
Caused no significant body weight changes, indicating good tolerability.

Animal Model:

Balb/c (female, subacute toxicity study)^[1]
Dosage:

30 mg/kg; 100 mg/kg; 300 mg/kg
Administration:

p.o.; once daily; 14 days
Result:

Caused no mortality or significant body weight loss in any treatment group.
Showed no significant decreases in complete blood count or serum biochemical parameters at doses of 100 and 300 mg/kg.

Animal Model:

Balb/c (acute toxicity study)^[1]
Dosage:

500 mg/kg; 1000 mg/kg
Administration:

p.o.; single dose
Result:

Caused no mortality or significant body weight changes over the 14-day observation period.

Chemical Information

Molecular Weight 448.49
Formula C₂₅H₂₅FN₄O₃
SMILES

FC1=CC=CC(C(CO[C@@H](CN2CCC(C3=CC=C(C(NC)=O)N=C3)=CC2)C4)=C4N5)=C1C5=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Protocols

All Cell Biology Animals and Diseases

Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Guo Z, et al. Discovery, Synthesis, and Biological Evaluation of 1,3,4,5-Tetrahydro-6H-pyrano[4,3-c]isoquinolin-6-one Derivatives as Novel and Highly Selective PARP1 Inhibitors. Journal of medicinal chemistry. 2026 Aug 13;69(15):18051-18075.

Calculators

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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PARP1-IN-60

All PARP Isoforms