PARP1-IN-6 is a dual tubulin/PARP-1 inhibitor with IC50 values of 0.94 and 0.48 μM, respectively.
分子量
266.27
Formula
C16H11FN2O
CAS 号
1654735-36-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Zheng L, et al. Discovery of a Dual Tubulin and Poly(ADP-Ribose) Polymerase-1 Inhibitor by Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, and Biological Evaluation. J Med Chem. 2021 Nov 11;64(21):15702-15715.
PARP10/15-IN-2 (Compound 8h) is a potent PARP10 and PARP15 dual inhibitor with IC50 values of 0.15 µM and 0.37 µM against PARP10 and PARP15, respectively. PARP10/15-IN-2 is able to enter cells and rescue cells from apoptosis[1].
IC50 & Target
PARP10
0.15 μM (IC50)
PARP15
0.37 μM (IC50)
分子量
286.26
Formula
C15H11FN2O3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Nizi MG, et al. Potent 2,3-dihydrophthalazine-1,4-dione derivatives as dual inhibitors for mono-ADP-ribosyltransferases PARP10 and PARP15. Eur J Med Chem. 2022 Jul 5;237:114362.
PARP10/15-IN-3 (Compound 8a) is a potent PARP10 and PARP15 dual inhibitor with IC50 values of 0.14 µM and 0.40 µM against PARP10 and PARP15, respectively. PARP10/15-IN-3 is able to enter cells and rescue cells from apoptosis[1].
IC50 & Target
PARP10
0.14 μM (IC50)
PARP15
0.40 μM (IC50)
分子量
232.24
Formula
C12H12N2O3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Nizi MG, et al. Potent 2,3-dihydrophthalazine-1,4-dione derivatives as dual inhibitors for mono-ADP-ribosyltransferases PARP10 and PARP15. Eur J Med Chem. 2022 Jul 5;237:114362.
PARP1/2/TNKS1/2-IN-1 (Compound I-9) is a dual PARP-1, PARP-2, TNKS1 and TNKS2 inhibitor with IC50 values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM against PARP-1, PARP-2, TNKS1 and TNKS2, respectively. PARP1/2/TNKS1/2-IN-1 exhibits favorable synergistic antitumor efficacy and induces apoptosis[1].
IC50 & Target
PARP-1
0.25 nM (IC50)
PARP-2
1.2 nM (IC50)
TNKS2
4.15 nM (IC50)
TNKS1
13.5 nM (IC50)
分子量
685.70
Formula
C38H32FN7O5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Xu Y, et al. Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy. Eur J Med Chem. 2022 Jul 5;237:114417.
PARP-1-IN-1 is a high selective and orally active PARP-1 inhibitor (IC50=0.96 nM). PARP-1-IN-1 has well tolerance and remarkable single dose activity in the MDA-MB-436 xenotransplantation model[1].
体外研究 (In Vitro)
PARP-1-IN-1 (compound Y49) (48 hours) has effective inhibition on different cancer cells (IC50s of 9.64, 123.5 106.3 μM for MX-1, MCF7 and A548 cells, respectively)[1]. PARP-1-IN-1 (2.5-10 μM, 48 hours) successfully inhibits the activity of PARP-1 and reduces the production of PAR in A549 cells, which is dose-dependent to some extent[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
A549 cells
Concentration:
2.5 μM, 5 μM and 10 μM
Incubation Time:
48h
Result:
Inhibited the activity of PARP-1 successfully and reduced the production of PAR in cancer cells. PARP-1-IN-1 was dose-dependent to some extent.
体内研究 (In Vivo)
PARP-1-IN-1 (compound Y49) (50 mg/kg/day; p.o.; daily for 18 days) inhibits the growth of MDA-MB-436 tumor in BALB/c nude mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Inhibited the growth of MDA-MB-436 tumor significantly, and no significant change in the body weight of PARP-1-IN-1 treated mice.
分子量
392.47
Formula
C23H25FN4O
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Yu J, et al. Structure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2. Eur J Med Chem. 2022;227:113898.
PARP-1-IN-1 is a high selective and orally active PARP-1 inhibitor (IC50=0.96 nM). PARP-1-IN-1 has well tolerance and remarkable single dose activity in the MDA-MB-436 xenotransplantation model[1].
体外研究 (In Vitro)
PARP-1-IN-1 (compound Y49) (48 hours) has effective inhibition on different cancer cells (IC50s of 9.64, 123.5 106.3 μM for MX-1, MCF7 and A548 cells, respectively)[1]. PARP-1-IN-1 (2.5-10 μM, 48 hours) successfully inhibits the activity of PARP-1 and reduces the production of PAR in A549 cells, which is dose-dependent to some extent[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
A549 cells
Concentration:
2.5 μM, 5 μM and 10 μM
Incubation Time:
48h
Result:
Inhibited the activity of PARP-1 successfully and reduced the production of PAR in cancer cells. PARP-1-IN-1 was dose-dependent to some extent.
体内研究 (In Vivo)
PARP-1-IN-1 (compound Y49) (50 mg/kg/day; p.o.; daily for 18 days) inhibits the growth of MDA-MB-436 tumor in BALB/c nude mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Inhibited the growth of MDA-MB-436 tumor significantly, and no significant change in the body weight of PARP-1-IN-1 treated mice.
分子量
392.47
Formula
C23H25FN4O
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Yu J, et al. Structure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2. Eur J Med Chem. 2022;227:113898.
PARP-1-IN-1 is a high selective and orally active PARP-1 inhibitor (IC50=0.96 nM). PARP-1-IN-1 has well tolerance and remarkable single dose activity in the MDA-MB-436 xenotransplantation model[1].
体外研究 (In Vitro)
PARP-1-IN-1 (compound Y49) (48 hours) has effective inhibition on different cancer cells (IC50s of 9.64, 123.5 106.3 μM for MX-1, MCF7 and A548 cells, respectively)[1]. PARP-1-IN-1 (2.5-10 μM, 48 hours) successfully inhibits the activity of PARP-1 and reduces the production of PAR in A549 cells, which is dose-dependent to some extent[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
A549 cells
Concentration:
2.5 μM, 5 μM and 10 μM
Incubation Time:
48h
Result:
Inhibited the activity of PARP-1 successfully and reduced the production of PAR in cancer cells. PARP-1-IN-1 was dose-dependent to some extent.
体内研究 (In Vivo)
PARP-1-IN-1 (compound Y49) (50 mg/kg/day; p.o.; daily for 18 days) inhibits the growth of MDA-MB-436 tumor in BALB/c nude mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Inhibited the growth of MDA-MB-436 tumor significantly, and no significant change in the body weight of PARP-1-IN-1 treated mice.
分子量
392.47
Formula
C23H25FN4O
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Yu J, et al. Structure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2. Eur J Med Chem. 2022;227:113898.
PARP1/BRD4-IN-1 is a potent and high selective PARP1/BRD4 inhibitor (IC50s of 49 and 202 nM in PARP1 and BRD4, respectively). PARP1/BRD4-IN-1 represses the expression and activity of PARP1 and BRD4 to synergistically inhibit the malignant growth of pancreatic cancer cells[1].
IC50 & Target
BRD4
202 nM (IC50)
PARP1
49 nM (IC50)
体外研究 (In Vitro)
PARP1/BRD4-IN-1 (compound III-7) (0-2 μM; 3-7 days) has potent inhibition of the growth of cancer cell lines[1]. PARP1/BRD4-IN-1 (0, 1, 2 μM; 4 days) can significantly inhibit the expression of PARP1 and BRD4 at 2 μM in SW1990 cells[1]. PARP1/BRD4-IN-1 (1, 2 μM; 4 days) arrests the cell cycle at G0/G1 and G2/M phase in SW1990 cells[1]. PARP1/BRD4-IN-1 (0, 1, 2 μM; 4 days) has the potent efficacy on the apoptosis of SW1990 cells at 2 μM[1]. PARP1/BRD4-IN-1 (1, 2 μM; 4 days) regulates the expression of HEXIM1, c-Myc, FOXO1, MDC1 and TOPBP1 to enhance the inhibition of DNA repair in SW1990 cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Showed potent inhibition of the growth of cancer cell lines.
Western Blot Analysis
Cell Line:
SW1990[1]
Concentration:
0, 1, 2 μM
Incubation Time:
4 days
Result:
Significantly inhibited the expression of PARP1 and BRD4 at 2 μM.
Cell Cycle Analysis
Cell Line:
SW1990[1]
Concentration:
1, 2 μM
Incubation Time:
4 days
Result:
Arrested the cell cycle at G0/G1 and G2/M phase.
Apoptosis Analysis
Cell Line:
SW1990[1]
Concentration:
0, 1, 2 μM
Incubation Time:
4 days
Result:
Showed potent efficacy on the apoptosis of SW1990 cells at 2 μM.
体内研究 (In Vivo)
PARP1/BRD4-IN-1 (30mg/kg; intraperitoneal injection for 28 days) can significantly inhibit the tumor size and weight, and does not cause significant damage of the kidney, lung, spleen, liver and heart in mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Significantly inhibited the tumor size and weight and did not cause significant damage of the kidney, lung, spleen, liver and heart.
分子量
506.56
Formula
C29H26N6O3
CAS 号
2758117-74-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Huang SH, et al. Design, synthesis and mechanism studies of novel dual PARP1/BRD4 inhibitors against pancreatic cancer. Eur J Med Chem. 2022;230:114116.
PARP1/BRD4-IN-1 is a potent and high selective PARP1/BRD4 inhibitor (IC50s of 49 and 202 nM in PARP1 and BRD4, respectively). PARP1/BRD4-IN-1 represses the expression and activity of PARP1 and BRD4 to synergistically inhibit the malignant growth of pancreatic cancer cells[1].
IC50 & Target
BRD4
202 nM (IC50)
PARP1
49 nM (IC50)
体外研究 (In Vitro)
PARP1/BRD4-IN-1 (compound III-7) (0-2 μM; 3-7 days) has potent inhibition of the growth of cancer cell lines[1]. PARP1/BRD4-IN-1 (0, 1, 2 μM; 4 days) can significantly inhibit the expression of PARP1 and BRD4 at 2 μM in SW1990 cells[1]. PARP1/BRD4-IN-1 (1, 2 μM; 4 days) arrests the cell cycle at G0/G1 and G2/M phase in SW1990 cells[1]. PARP1/BRD4-IN-1 (0, 1, 2 μM; 4 days) has the potent efficacy on the apoptosis of SW1990 cells at 2 μM[1]. PARP1/BRD4-IN-1 (1, 2 μM; 4 days) regulates the expression of HEXIM1, c-Myc, FOXO1, MDC1 and TOPBP1 to enhance the inhibition of DNA repair in SW1990 cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Showed potent inhibition of the growth of cancer cell lines.
Western Blot Analysis
Cell Line:
SW1990[1]
Concentration:
0, 1, 2 μM
Incubation Time:
4 days
Result:
Significantly inhibited the expression of PARP1 and BRD4 at 2 μM.
Cell Cycle Analysis
Cell Line:
SW1990[1]
Concentration:
1, 2 μM
Incubation Time:
4 days
Result:
Arrested the cell cycle at G0/G1 and G2/M phase.
Apoptosis Analysis
Cell Line:
SW1990[1]
Concentration:
0, 1, 2 μM
Incubation Time:
4 days
Result:
Showed potent efficacy on the apoptosis of SW1990 cells at 2 μM.
体内研究 (In Vivo)
PARP1/BRD4-IN-1 (30mg/kg; intraperitoneal injection for 28 days) can significantly inhibit the tumor size and weight, and does not cause significant damage of the kidney, lung, spleen, liver and heart in mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Significantly inhibited the tumor size and weight and did not cause significant damage of the kidney, lung, spleen, liver and heart.
分子量
506.56
Formula
C29H26N6O3
CAS 号
2758117-74-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Huang SH, et al. Design, synthesis and mechanism studies of novel dual PARP1/BRD4 inhibitors against pancreatic cancer. Eur J Med Chem. 2022;230:114116.
PARP1/BRD4-IN-1 is a potent and high selective PARP1/BRD4 inhibitor (IC50s of 49 and 202 nM in PARP1 and BRD4, respectively). PARP1/BRD4-IN-1 represses the expression and activity of PARP1 and BRD4 to synergistically inhibit the malignant growth of pancreatic cancer cells[1].
IC50 & Target
BRD4
202 nM (IC50)
PARP1
49 nM (IC50)
体外研究 (In Vitro)
PARP1/BRD4-IN-1 (compound III-7) (0-2 μM; 3-7 days) has potent inhibition of the growth of cancer cell lines[1]. PARP1/BRD4-IN-1 (0, 1, 2 μM; 4 days) can significantly inhibit the expression of PARP1 and BRD4 at 2 μM in SW1990 cells[1]. PARP1/BRD4-IN-1 (1, 2 μM; 4 days) arrests the cell cycle at G0/G1 and G2/M phase in SW1990 cells[1]. PARP1/BRD4-IN-1 (0, 1, 2 μM; 4 days) has the potent efficacy on the apoptosis of SW1990 cells at 2 μM[1]. PARP1/BRD4-IN-1 (1, 2 μM; 4 days) regulates the expression of HEXIM1, c-Myc, FOXO1, MDC1 and TOPBP1 to enhance the inhibition of DNA repair in SW1990 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Showed potent inhibition of the growth of cancer cell lines.
Western Blot Analysis
Cell Line:
SW1990[1]
Concentration:
0, 1, 2 μM
Incubation Time:
4 days
Result:
Significantly inhibited the expression of PARP1 and BRD4 at 2 μM.
Cell Cycle Analysis
Cell Line:
SW1990[1]
Concentration:
1, 2 μM
Incubation Time:
4 days
Result:
Arrested the cell cycle at G0/G1 and G2/M phase.
Apoptosis Analysis
Cell Line:
SW1990[1]
Concentration:
0, 1, 2 μM
Incubation Time:
4 days
Result:
Showed potent efficacy on the apoptosis of SW1990 cells at 2 μM.
体内研究 (In Vivo)
PARP1/BRD4-IN-1 (30mg/kg; intraperitoneal injection for 28 days) can significantly inhibit the tumor size and weight, and does not cause significant damage of the kidney, lung, spleen, liver and heart in mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Significantly inhibited the tumor size and weight and did not cause significant damage of the kidney, lung, spleen, liver and heart.
分子量
506.56
Formula
C29H26N6O3
CAS 号
2758117-74-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Huang SH, et al. Design, synthesis and mechanism studies of novel dual PARP1/BRD4 inhibitors against pancreatic cancer. Eur J Med Chem. 2022;230:114116.
PARP-2-IN-1 is a potent and selective PARP-2 inhibitor with an IC50 of 11.5 nM.
IC50 & Target
PARP-2
11.5 nM (IC50)
分子量
465.40
Formula
C21H19F4N5O3
CAS 号
2115698-83-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Zhao H, et al. Discovery of novel quinazoline-2,4(1H,3H)-dione derivatives as potent PARP-2 selective inhibitors. Bioorg Med Chem. 2017 Aug 1;25(15):4045-4054.
Rucaparib (AG014699) is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib has the potential for castration-resistant prostate cancer (CRPC) research[1][2][3][4].
IC50 & Target[1][2]
PARP-1
1.4 nM (Ki)
PARP-2
PARP-3
体外研究 (In Vitro)
Rucaparib (AG014699) is a possible N-demethylation metabolite of AG14644[1]. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) is cytotoxic and has the LC50 being 5 μM in Capan-1 (BRCA2 mutant) cells and only 100 nM in MX-1 (BRCA1 mutant) cells[2]. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions[5]. Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells[6].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Rucaparib (AG014699) and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) results in a 50% increase in the temozolomide-induced tumor growth delay[1]. Rucaparib (10 mg/kg for i.p. or 50, 150 mg/kg for p.o.; daily for 5 days per week for 6 weeks) significantly inhibits the growth of the tumor, and there is one complete tumor regression and two persistent partial regressions[2]. Rucaparib (150 mg/kg; p.o.; once per week for 6 weeks or three times per week for 6 weeks) has greatest antitumor effect with three complete regressions[2]. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts[6].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Female CD-1 nude mice aged 10-12 weeks with Capan-1 cells[2]
Dosage:
10 mg/kg for i.p. or 50, 150 mg/kg for p.o.
Administration:
IP or PO
Result:
Significantly inhibited the growth of the tumor.
Clinical Trial
分子量
323.36
Formula
C19H18FN3O
CAS 号
283173-50-2
中文名称
瑞卡帕布；鲁卡帕尼
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 25 mg/mL (77.31 mM; ultrasonic and adjust pH to 4 with HCl)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
[1]. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.
[2]. J Murray, et al. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84.
[3]. Daniel RA, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249.
[4]. Jianneng Li, et al. Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation. Sci Transl Med. 2021 May 26;13(595):eabe8226.
[5]. Hunter JE, et al. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.
[6]. Matt Shirley, et al. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246.
AZ3391 is a potent inhibitor of PARP. AZ3391 is a quinoxaline derivative. PARP family of enzymes play an important role in a number of cellular processes, such as replication, recombination, chromatin remodeling, and DNA damage repair. AZ3391 has the potential for the research of diseases and conditions occurring in tissues in the central nervous system, such as the brain and spinal cord (extracted from patent WO2021260092A1, compound 23)[1].
分子量
438.50
Formula
C23H27FN6O2
CAS 号
2756333-42-1
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Martin John Packer, et al. Quinoxaline derivatives as anti-cancer drugs. Patent WO2021260092A1.
PARP/PI3K-IN-1 (compound 15) is a potent PARP/PI3K inhibitor with pIC50 values of 8.22, 8.44, 8.25, 6.54, 8.13, 6.08 for PARP-1, PARP-2, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively. PARP/PI3K-IN-1 is a highly effective anticancer compound targeted against a wide range of oncologic diseases[1].
IC50 & Target[1]
PARP-1
8.22 (pIC50)
PARP-2
8.44 (pIC50)
PI3Kα
8.25 (pIC50)
PI3Kδ
8.13 (pIC50)
PI3Kγ
6.08 (pIC50)
PI3Kβ
6.54 (pIC50)
体外研究 (In Vitro)
PARP/PI3K-IN-1 (compound 15; 1 μM; 72 hours) leads to a significant increase in cell apoptosis[1]. PARP/PI3K-IN-1 (1 μM; 72 hours) reduces the autophosphorylation levels of AKT and S6 while increases the autophosphorylation level of ERK after treating cells, indicating that it can inhibit the PI3K pathway and activate the ERK pathway[1]. PARP/PI3K-IN-1 (1 μM) displays a strong capability to downregulate the expression of BRCA1/2 at the mRNA level in MDA-MB-468 cancer cells[1]. PARP/PI3K-IN-1 not only shows significant inhibitory activity against BRCA-deficient cells HCC1937 and HCT116, but also displays potent anti-proliferative activity against BRCA-proficient cells MDA-MB-231 and MDA-MB-468[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Apoptosis Analysis[1]
Cell Line:
MDA-MB-468 cancer cells
Concentration:
1 μM
Incubation Time:
72 hours
Result:
Led to a significant increase in cell apoptosis.
Western Blot Analysis[1]
Cell Line:
MDA-MB-468 cancer cells
Concentration:
1 μM
Incubation Time:
72 hours
Result:
Reduced the autophosphorylation levels of AKT and S6 while increased the autophosphorylation level of ERK after treating cells.
体内研究 (In Vivo)
PARP/PI3K-IN-1 (i.p.; 50 mg/kg; twice daily (BID) for 34 consecutive days) significantly suppresses the tumor growth[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Six-week-old male BALB/c nude mice with MDA-MB-468 cells[1]
Dosage:
50 mg/kg
Administration:
i.p.; twice daily (BID) for 34 consecutive days
Result:
Significantly suppressed the tumor growth.
分子量
660.62
Formula
C33H28F4N8O3
CAS 号
2337386-47-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Wang J, et al.Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy.J Med Chem. 2020 Jan 9;63(1):122-139.
iRucaparib-AP6 is a highly efficient and specific PARP1 degrader based on Rucaparib by using the PROTAC approach. iRucaparib-AP6, a non-trapping PARP1 degrader, blocks both the catalytic activity and scaffolding effects of PARP1[1].
体外研究 (In Vitro)
iRucaparib-AP6 (0-10 μM; 24 hours) decreases PARP-1 level in a dose dependent manner, exhibits a half-maximal degrading concentration (DC50) of 82 nM (Dmax = 92%)[1]. iRucaparib-AP6 (0-20 μM; 24 hours) induces degradation of PARP1 at low concentrations[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Primary rat neonatal cardiomyocyte cells
Concentration:
0.001 μM; 0.01 μM; 0.1 μM; 1 μM; 10 μM
Incubation Time:
24 hours
Result:
Decreased PARP-1 level in primary rat neonatal cardiomyocyte cells.
Dual PARP EGFR ligand for PROTAC Chemical Structure
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
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生物活性
Dual PARP EGFR ligand for PROTAC incorporates a ligand for PARP and EGFR , and a PROTAC linker, which recruit E3 ligases (such as VHL, CRBN, MDM2, and IAP). Dual PARP EGFR ligand for PROTAC can be used in the synthesis of DP-C-4, which is CRBN-based dual PROTAC for simultaneous degradation of EGFR and PARP[1].
分子量
1020.52
Formula
C53H56ClF2N9O8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Mengzhu Zheng, et al. Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP. J Med Chem. 2021 May 26.
PARP1-IN-5 is a low toxicity, orally active, potent and selective PARP-1 inhibitor (IC50 =14.7 nM). PARP1-IN-5 can be used for the research of cancer[1].
IC50 & Target[1]
PARP-1
14.7 nM (IC50)
PARP-2
0.9 μM (IC50)
体外研究 (In Vitro)
PARP1-IN-5 (0.1~10 μM; A549 cells) can significantly increase the cytotoxicity of CBP on A549 cells in a dose-dependent manner. PARP1-IN-5 (0.1~10 μM; SK-OV-3 cells) decreases the expressions of MCM2-7. PARP1-IN-5 (0.1~320 μM; A549 cells) has little cytotoxic effects on A549 cells. PARP1-IN-5 (SK-OV-3 cells) can significantly decrease the PAR level[1]. PARP1-IN-5 exerts antitumor effects through PARP-1. PARP1-IN-5 could increase the γ-H2AX expression[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
PARP1-IN-5 (1000 mg/kg; p.o.) shows that there is no significant difference in the body weight and blood routine[1]. PARP1-IN-5 (25 and 50 mg/kg; p.o.; 12 days) significantly enhances the inhibitory effect of carboplatin on A549 cells at 50 mg/kg[1]. PARP1-IN-5 (50 mg/kg; p.o.) positively correlates with the expression of PARP-1[1]. PARP1-IN-5 can upregulate the expression of γ-H2AX and decrease the expression of PAR[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Mice[1]
Dosage:
1000 mg/kg
Administration:
P.o.
Result:
There was no significant difference in the body weight and blood routine.
Animal Model:
Mice[1]
Dosage:
25 and 50 mg/kg
Administration:
P.o.; 12 days
Result:
Significantly enhanced the inhibitory effect of CBP on A549 cells at 50 mg/kg.
Animal Model:
Male Sprague−Dawley (SD) rats[1]
Dosage:
50 mg/kg (Pharmacokinetic Analysis)
Administration:
P.o.; 12 days
Result:
Positively correlated with the expression of PARP-1.
分子量
464.53
Formula
C25H24N2O5S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Long H, et al. Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer. J Med Chem. 2021;64(16):12089-12108.
E7449 is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using 32P-NAD+ as substrate.
IC50 & Target[1]
PARP2
1 nM (IC50)
PARP1
2 nM (IC50)
TNKS1
50 nM (IC50)
TNKS2
50 nM (IC50)
体外研究 (In Vitro)
E7449 is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using 32P-NAD+ as substrate. E7449 shows no obvious inhibiotry effects on PARP3 or PARPs 6-16. E7449 traps PARP1 onto damaged DNA, and affects DNA repair pathways beyond homologous recombination (HR). E7449 most potnetly suppresses cells deficient in components of the HR pathway (BRCA1 and 2, CtIP, Rad54). E7449 (10 μM) inhibits Wnt signaling in SW480 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
E7449 moderately inhibits the growth of tumors at 100 mg/kg, and significantly ehhances the inhibition via 10, 30 and 100 mg/kg oral dosing in combination with temozolomide (TMZ) in the mouse melanoma B16-F10 isograft model. E7449 (30 or 100 mg/kg, p.o.) inhibits PARP, shows anti-tumor activity, and is well-tolerated without any obvious body weight loss or deaths in a BRCA mutant xenograft model. E7449 (30, 100 or 300 mg/kg, p.o.) suppresses re-growth of hair in a dose dependent manner, and blocks Wnt signaling in C57BL/6 mice. E7449 (100 mg/kg, p.o.) combined with MEK inhibitor exhibits antitumor activity in a Wnt1 subcutaneous model (mammary tumors initially isolated from Wnt1 (int-1) transgenic mice)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
317.34
Formula
C18H15N5O
CAS 号
1140964-99-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 6.4 mg/mL (20.17 mM; Need ultrasonic and warming)
[1]. McGonigle S, et al. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23.
Kinase Assay [1]
Briefly, 24 to 48 h after transfection, cells are washed 3× in ice-cold PBS and lysed for 20 min on ice in cell lysis buffer (CLB: 50 mM HEPES, pH 7.4, 150 mM NaCl, 1 mM MgCl2, 1 mM EGTA, 1 mM DTT, 1% TritonX-100, 1 μg/mL leupeptin, aprotinin, pepstatin, PMSF). Lysates are subject to ultracentrifugation at 100,000 g for 30 min. Cleared lysates are incubated for 1 h at 4°C with anti-GFP antibody (3E6) and pre-bound protein A magnetic beads. Beads are then washed 1 × 5 min in CLB, followed by 3 × 10 min washes in CLB containing 1 M NaCl, and 1 × 5 min wash in PARP reaction buffer (PRB; 50 mM Tris, pH 7.5, 50 mM NaCl, 0.5 mM DTT, 0.1% TritonX-100, 1 μg/mL leupeptin, aprotinin, pepstatin). NAD+ incorporation reactions are performed in PRB containing 10 μM NAD+ supplemented with 32P-NAD+ at 1:20 ratio for 30 min at 25°C. For PARPs with low incorporation signals (PARP4, 5a and 16), NAD+ incorporation is performed at 1:5 ratio for 1 h at 25°C. Beads are then re-suspended in Laemmli sample buffer, heated to 65°C for 10 min, the beads removed using a magnet, and the supernatant spotted onto Whatman paper. Samples are analyzed via phosphorimaging[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
Proliferation assays are performed in a panel of 32 isogenic DT40 cell lines, in which each line is deficient in a distinct DNA repair gene. Cells are seeded and incubated with test compound at various concentrations for 2-3 days (∼ 8 cell cycles). Cell growth is assessed using XTT and IC50 values are calculated using the GraphPad Prism 5 software version 5.02. Each experiment is conducted in duplicate and a minimum of 3 separate experiments are performed. Human breast cancer cell lines, HCC1143, HCC70, HCC1806, MDA-MB-436, T47D, MDA-MB-157, MDA-MB-231, MDA-MB-468, MDA-MB-453, BT-20 and Hs578T are used. For cell line panel assays, cells are maintained and assayed in RPMI 1640 or DMEM medium containing 10% FBS. For proliferation assays cells are plated at low density in 96 well plates. E7449 is added at various concentrations and plates incubated for a total of 8 days; compound and medium are replenished on day 4. Cell growth is assessed using the CellTiter-Glo cell viability assay. Each experiment is conducted in duplicate and a minimum of 3 separate experiments are performed[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Temozolomide (TMZ) combination in B16-F10 isograft model: female C57BL/6 mice are inoculated subcutaneously with B16-F10 cells (2 × 105). Following randomization by body weight, drug treatment is initiated 1 day post-inoculation. Both E7449 and TMZ are formulated in 0.5% methyl cellulose and orally administrated once per day. TMZ is administered daily on days 1 to 5 at 50 mg/kg as a single agent or in combination. E7449 is administered daily on days 1 to 7 at doses of 10, 30 and 100 mg/kg in combination with TMZ and at a dose of 100 mg/kg as a single agent. The control group is treated with vehicle (0.5% methyl cellulose in water). E7449 or vehicle is administered first and when dosing of all animals is complete TMZ is administered to animals receiving the combination[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. McGonigle S, et al. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23.
