There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
PARP1, also called as Poly(ADP-ribose) polymerase, is involved in the signaling of DNA damage. It can recognize and bind DNA single or double-strand breaks, thus possessing various cellular function, including regulation of apoptosis and chromosome stability, gene amplification and transcription, as well as cell division and differentiation. PARP-2 is the closest homolog of PARP1 (~62% similarity in catalytic domain) and compensates for PARP-1 activity in DNA single-strand break. MK-4827 Tosylate is the tosylate form of MK-4827. MK-4827 is potent inhibitor of PARP1 and PARP2 with IC50 values of 3.8nM and 2.1nM (measured by PARP isoform TCA assays), respectively, at least a 100-fold selectivity over PARP-3, V-PARP, and tankyrase-1. MK-4827 inhibited PARP activity with EC50 of 4nM and preferentially suppressed proliferation of MDA-MB-436 cells carrying BRCA-1 mutation with CC50 value of 18nM and CAPAN-1 cells carrying BRCA-2 mutantation with CC50 value of 90nM. Oral treatment with MK-4827 at either 100 mg/kg q.d. or 50 mg/kg b.i.d. for 33 days repressed tumor growth in a BRCA-1 mutant MDA-MB-436 xenograft model[1].Oral administration of MK-4827 at a dose of 50mg/kg once daily radiosensitized all four tumors regardless of the p53 status, including Calu-6, H460, A549 and MDA-MB-231, with reduced PAR levels in tumors[2].
作用机制
MK-4827 is a nicotinamide derivate, which can compete with NAD+ for the PARP catalytic site.[3]
Niraparib tosylate/尼拉帕尼对苯甲磺酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MDA-MB-231
50 nM
24 h
To evaluate the effect of Niraparib combined with CDK4/6 inhibitors on DNA damage in RB-proficient cells. The results showed that the combination significantly increased the number of γ-H2AX foci, indicating increased DNA damage.
Cell Death Dis. 2020 Apr 6;11(4):219.
MDA-MB-468
50 nM
24 h
To evaluate the effect of Niraparib combined with CDK4/6 inhibitors on DNA damage in RB-deficient cells. The results showed that the combination significantly increased the number of γ-H2AX foci, indicating increased DNA damage.
Cell Death Dis. 2020 Apr 6;11(4):219.
SNU-251
100 nM
To evaluate the effect of Niraparib on SNU-251 cells, results showed that SNU-251 cells formed fewer colonies in the presence of Niraparib.
Nat Commun. 2019 Dec 11;10(1):5661.
HeLa LT ATRX knockout clones
5 µM
48 h
Through C-circle assay and APB analysis, it was found that Niraparib treatment of ATRX knockout HeLa LT cells induced an increase in ALT markers, indicating that Niraparib induces the ALT pathway by trapping PARP1 protein.
Nucleic Acids Res. 2023 Jul 21;51(13):6509-6527.
MDA-MB-231 cells
12.5 µM
4, 8 or 24 h
To study the effect of Niraparib on the transcriptomic dynamics of MDA-MB-231 cells, revealing heterogeneous responses after drug treatment.
Mol Syst Biol. 2021 Apr;17(4):e10060.
RMC2C
10 μM
120 h
To evaluate the inhibitory effect of Niraparib on RMC2C cells
Cancer Cell. 2020 May 11;37(5):720-734.e13.
RMC219
10 μM
120 h
To evaluate the inhibitory effect of Niraparib on RMC219 cells
Cancer Cell. 2020 May 11;37(5):720-734.e13.
Niraparib tosylate/尼拉帕尼对苯甲磺酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
A2780wt or A2780/P-gp ovarian cancer model
Oral
50 mg/kg
Single dose, euthanized 2h after treatment
To study the tumor distribution of Niraparib in ovarian cancer models, results showed homogeneous distribution in A2780wt tumors and heterogeneous distribution in A2780/P-gp tumors
Int J Biol Sci. 2020 Feb 21;16(8):1363-1375
Mice
A2780wt and A2780/P-gp ovarian cancer models
Oral
50 mg/kg
Single dose, euthanized 2 hours post-treatment
To study the tumor distribution of Niraparib in ovarian cancer models, results showed homogeneous distribution in A2780wt model and heterogeneous distribution in A2780/P-gp model
Int J Biol Sci. 2020 Feb 21;16(8):1363-1375
Mice
MC38 subcutaneous tumor model
Oral
4 mg/kg
Once daily for several days
To evaluate the effect of Niraparib in enhancing immune response during radiotherapy, results showed that Niraparib increased the production of Ifnb and Cxcl10.
Nat Commun. 2022 Nov 19;13(1):7107
Nude mice
MDA-MB-231 and MDA-MB-468 xenograft models
Oral
4 mg/kg
Twice daily, until tumors reached 1200 mm³ or showed necrosis
To evaluate the anti-tumor effect of Niraparib combined with CDK4/6 inhibitors in RB-proficient and RB-deficient xenograft models. The results showed that the combination significantly reduced tumor volume and was well tolerated.
Cell Death Dis. 2020 Apr 6;11(4):219.
Mice
Patient-derived tumor xenografts (PDXs) from breast cancer patients
Oral
50 mg/kg or 75 mg/kg
Daily for 28 days
To evaluate the antitumor activity of Niraparib in breast cancer PDX models, results showed significant antitumor effects in some models.
EMBO Mol Med. 2018 Dec;10(12):e9172
Mice
NSG mice
Oral
150 mg/kg
Twice daily for 10 days
To evaluate the effect of Niraparib on tumor growth in mice, results showed that Niraparib significantly delayed tumor growth.
Nat Commun. 2019 Dec 11;10(1):5661.
Mice
RMC2X PDX model
Oral
50 mg/kg
Once daily for 25 days
To evaluate the antitumor effect of Niraparib on the RMC2X PDX model
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