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
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
Description
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[1].
IC50 & Target
[1]|
PARP1 2.4 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
2.35 nM
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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
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Antiproliferative activity against BRCA-mutant MDA-MB-436 cells.
Antiproliferative activity against BRCA-mutant MDA-MB-436 cells.
|
42593943 |
| SUM149PT | IC50 |
2.82 nM
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Antiproliferative activity against BRCA-mutant SUM149PT cells.
Antiproliferative activity against BRCA-mutant SUM149PT cells.
|
42593943 |
| CAPAN-1 | IC50 |
832 nM
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Antiproliferative activity against BRCA-wild-type CAPAN-1 cells.
Antiproliferative activity against BRCA-wild-type CAPAN-1 cells.
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42593943 |
| MDA-MB-231 | IC50 |
197 nM
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Antiproliferative activity against BRCA-wild-type MDA-MB-231 cells.
Antiproliferative activity against BRCA-wild-type MDA-MB-231 cells.
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42593943 |
| Vero | IC50 |
1845 nM
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Antiproliferative activity against normal VERO cells.
Antiproliferative activity against normal VERO cells.
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42593943 |
| H9c2 | IC50 |
2647 nM
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Antiproliferative activity against normal H9C2 cells.
Antiproliferative activity against normal H9C2 cells.
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42593943 |
In Vitro
Anti-cancerCell Cycle RegulationOthers
Anti-cancer
PARP1-IN-60 ((R)-A17) (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 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].
Cell Cycle Regulation
Anti-cancer
PARP1-IN-60 (1-100 nM; 72 h) induces dose-dependent G2/M phase arrest in MDA-MB-436 cells[1].
Others
PARP1-IN-60 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 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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
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Cell Line:MDA-MB-436 (BRCA-deficient), DLD-1 wild-type, DLD-1 BRCA2-knockout
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Concentration:0.1-100 nM
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Incubation Time:10 days
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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]
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Cell Line:MDA-MB-436
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Concentration:1-100 nM
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Incubation Time:72 h
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Result:Induced a dose-dependent decrease in S-phase cells.
Caused a corresponding accumulation of cells in G2/M phase.
Parmacokinetics
In Vivo
Anti-cancerOthers
Anti-cancer
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 (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].
Others
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].
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.
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Animal Model:NOD/SCID (female, 4-6 weeks old, 18-20 g, subcutaneous breast cancer xenograft model)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.; every other day
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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.
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Animal Model:Nu/Nu (female, 4-6 weeks old, subcutaneous colorectal cancer xenograft model)[1]
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Dosage:1 mg/kg; 3 mg/kg (in combination with liposomal irinotecan 2 mg/kg)
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Administration:p.o.; once daily; liposomal irinotecan: i.v.; twice weekly
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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.
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Animal Model:Balb/c (female, subacute toxicity study)[1]
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Dosage:30 mg/kg; 100 mg/kg; 300 mg/kg
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Administration:p.o.; once daily; 14 days
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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.
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Animal Model:Balb/c (acute toxicity study)[1]
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Dosage:500 mg/kg; 1000 mg/kg
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Administration:p.o.; single dose
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Result:Caused no mortality or significant body weight changes over the 14-day observation period.
Chemical Information
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Molecular Weight 448.49
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Formula C25H25FN4O3
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SMILES
FC1=CC=CC(C(CO[C@@H](CN2CCC(C3=CC=C(C(NC)=O)N=C3)=CC2)C4)=C4N5)=C1C5=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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PARP1-IN-60 Related Classifications
HY-189005 Related Classifications
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