PARP1-IN-34
PARP1-IN-34 (compound 30) is a selective PARP1 inhibitor with an IC50 of 0.32 nM. PARP1-IN-34 is a subnanomolar PARP1 inhibitor with >1000-fold selectivity against PARP2 with an IC50 of 326 nM. PARP1-IN-34 shows antitumor efficacy[1].
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- 화학식: C23H27N7O2
- 분자량:433.51
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보관:
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
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PARP1 0.32 nM (IC50) |
PARP2 326 nM (IC50) |
In Vitro
PARP1-IN-34 shows the PARP1 trapping with EC50s of 34.7, 65.9, 102.7 nM at 60, 120, 180 min, respectively[1].
PARP1-IN-34 shows very weak PARP2 trapping with an EC50 of 9882 nM[1].
PARP1-IN-34 (180min) formed a tighter PARP1-DNA trapping than Palacaparib (AZD-9574) (HY-145804)[1].
PARP1-IN-34 (10 nM, 72 h) stimulates DNA double-stands breaks in MDA-MB-436 cells.
PARP1-IN-34 (10 nM, 72 h) could increase the levels of γH2AX in MDA-MB-436 cells and causes more significant DNA damage in cells than AZD9574[1].
PARP1-IN-34 displays neglectable antiproliferation activities in these BRCA WT cells (CAL-148, 22RV1, and PC3 cell) and 293T normal cells (IC50 > 10,000 nM), in contrast to IC50 = 2.6 nM in BRCA-mutated MDA-MB-436 cells, which indicates that its cellular activity is PARP1inhibition-dependent[1].
PARP1-IN-34 is a highly selective PARP1inhibitor over other PARPs, including PARP2, PARP3, PARP5A, PARP5B,
PARP6, PARP7, PARP12, PARP14, and PARP15[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-436 cells
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Concentration:10 nM
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Incubation Time:72 h
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Result:Increased the levels of γH2AX at 10 nM in MDA-MB-436 cells and causes more significant DNA damage in cells than AZD9574
In Vivo
PARP1-IN-34 (10 mg/kg, p.o., daily, 35 days) has synergy with Carboplatin(HY-17393) in the SUM149PT xenograft model[1].
PARP1-IN-34 (5, 25 mg/kg, p.o., daily, 14 days) has minimal impact on RET(reduction of the reticulocyte) [1].
Pharmacokinetics of PARP1-IN-34 in the Mouse, Rat, and Dog.
| property | mouse | rat | dog | ||
| plasma protein unbound fraction | 0.012 | 0.067 | 0.022 | ||
| t1/2 (h) | 3.2 | 5.1 | 9.2 | ||
| V ss(L/kg) | 0.34 | 1.42 | 0.36 | ||
| CLp(mL/min/kg) | 2.0 | 4.9 | 0.58 | ||
| AUC(0-t)(ng・h r/mL) po | 45688 | 13622 | 15024 | ||
| F(%) | 132.4 | 93.1 | 67.3 |
| Compound | Olaparib | AZD5305 | AZD9574 | PARP1-IN-34 | |
| Potency | PARP1 IC50(nM) PARP2 IC50(nM) PARP 1/2 fold selectivity |
0.95 0.34 0.39 |
0.46 10 22 |
0.87 672 772 |
0.32 326 1019 |
In vivo efficacy in MDA-MB-436 | Dose of tumor regression ≥50% AUC (ng/ml hr) Unbound % in mice Free - drug AUC (ng/ml hr) |
100 mg/kg 31426 29.3% 9208 |
0.1 mg/kg 4043 2% 81 |
2 mg/kg 9776 4% 391 |
0.6 mg/kg 1039 1.2% 12.5 |
Hematox in rat | Dose of RET > 50%↓ AUC (ng/ml hr) Unbound % in rat Free - drug AUC (ng/ml hr) |
<100 mg/kg 55803 26.6% 14844 |
< 1 mg/kg 7505 2% 150.1 |
>100 mg/kg 308365 9.7% 29911 |
> 25 mg/kg 133541 6.7% 8947 |
Therapeutic index | Fold of Free - drug AUC | <1.61 | < 1.71 | >76.5 | >715 |
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