Olaparib(AZD2281 KU0059436) - 半岛电竞官方网址

Molecular Weight (MW)	434.46
Formula	C24H23FN4O3
CAS No.	763113-22-0
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility(In vitro)	DMSO: 86 mg/mL (197.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility(In vivo)	4% DMSO+30% PEG 300+ddH2O: 5 mg/mL
Synonyms	AZD2281, Ku-0059436; AZD2281; AZD-2281; AZD 2281; KU59436; KU-59436; KU 59436; KU0059436; KU-0059436; KU 0059436; Olaparib. trade name Lynparza Chemical Name: 4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one SMILES Code: O=C1NN=C(CC2=CC=C(F)C(C(N3CCN(C(C4CC4)=O)CC3)=O)=C2)C5=C1C=CC=C5

Molecular Weight (MW)

434.46

Formula

C24H23FN4O3

CAS No.

763113-22-0

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility(In vitro)

DMSO: 86 mg/mL (197.9 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility(In vivo)

4% DMSO+30% PEG 300+ddH2O: 5 mg/mL

Synonyms

AZD2281, Ku-0059436; AZD2281; AZD-2281; AZD 2281; KU59436; KU-59436; KU 59436; KU0059436; KU-0059436; KU 0059436; Olaparib. trade name Lynparza

Chemical Name: 4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one

SMILES Code: O=C1NN=C(CC2=CC=C(F)C(C(N3CCN(C(C4CC4)=O)CC3)=O)=C2)C5=C1C=CC=C5

In Vitro	In vitroactivity: Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50>1 μM). Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. Olaparib is hypersensitive to BRCA1-deficient cell lines (MDA-MB-463 and HCC1937), compared with BRCA1- and BRCA2-proficient cell lines (Hs578T, MDA-MB-231, and T47D). Olaparib is strongly sensitive to KB2P cells due to suppression of base excision repair by PARP inhibition, which may result in the conversion of single-strand breaks to double-strand breaks during DNA replication, thus activating BRCA2-dependent recombination pathways. Kinase Assay: To columns 1 through 10, 1 μL of Olaparib (in DMSO) is added, and 1 μL DMSO only is added to the positive (POS) and negative (NEG) control wells (columns 11 and 12, respectively) of a pretreated FlashPlate. PARP-1 is diluted 1:40 in buffer (buffer B: 10% glycerol (v/v), 25 mM HEPES, 12.5 mM MgCl2,50 mM KCl, 1 mM DTT, 0.01% NP-40 (v/v), pH 7.6) and 40 μL added to all 96 wells (final PARP-1 concentration in the assay is ~1 ng/μL). The plate is sealed and shaken at RT for 15 min. Following this, 10 μL of positive reaction mix (0.2 ng/μL of double-stranded oligonucleotide [M3/M4] DNA per well, 5 μM of NAD+ final assay concentration, and 0.075 μCi 3H-NAD+ per well) is added to the appropriate wells (columns 1-11). The negative reaction mix, lacking the DNA oligonucleotide, is added to column 12 (with the mean negative control value used as the background). The plate is resealed and shaken for a further 60 min at RT to allow the reaction to continue. Then, 50 μL of ice-cold acetic acid (30%) is added to each well to stop the reaction, and the plate is sealed and shaken for a further 60 min at RT. Tritiated signal bound to the FlashPlate is then determined in counts per minute (CPM) using the TopCount plate reader. Cell Assay: The cytotoxicity of Olaparib is measured by clonogenic assay. Olaparib is dissolved in DMSO and diluted by culture media before use. The cells (Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D) are seeded in six well plates and left to attach overnight. Then Olaparib is added at various concentrations and the cells are incubated for 7-14 days. After that the surviving colonies are counted for calculating the IC50.
In Vivo	Combining with temozolomide, Olaparib (10 mg/kg, p.o.) significantly suppresses tumor growth in SW620 xenografts. Olaparib shows great response to Brca1-/-;p53-/- mammary tumors (50 mg/kg i.p. per day), while no responses to HR-deficient Ecad-/-;p53-/- mammary tumors. Olaparib even does not show dose-limiting toxicity in tumor-bearing mice. Olaparib has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, Olaparib shows selectively inhibition to ATM (Ataxia Telangiectasia Mutated)-deficient tumor cells, which indicates to be a potential agent for treating ATM mutant lymphoid tumors.
Animal model	Granta-519–engrafted NOD/SCID mice
Formulation & Dosage	Dissolved in 50 mg/mL stocks in DMSO with 10% 2-hydroxyl-propyl-β-cyclodextrine/PBS; 50 mg/kg; i.p. injection
References	J Med Chem. 2008 Oct 23;51(20):6581-91; Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84; Blood. 2010 Nov 25;116(22):4578-87.

In Vitro

In vitroactivity: Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50>1 μM). Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. Olaparib is hypersensitive to BRCA1-deficient cell lines (MDA-MB-463 and HCC1937), compared with BRCA1- and BRCA2-proficient cell lines (Hs578T, MDA-MB-231, and T47D). Olaparib is strongly sensitive to KB2P cells due to suppression of base excision repair by PARP inhibition, which may result in the conversion of single-strand breaks to double-strand breaks during DNA replication, thus activating BRCA2-dependent recombination pathways.

Kinase Assay: To columns 1 through 10, 1 μL of Olaparib (in DMSO) is added, and 1 μL DMSO only is added to the positive (POS) and negative (NEG) control wells (columns 11 and 12, respectively) of a pretreated FlashPlate. PARP-1 is diluted 1:40 in buffer (buffer B: 10% glycerol (v/v), 25 mM HEPES, 12.5 mM MgCl2,50 mM KCl, 1 mM DTT, 0.01% NP-40 (v/v), pH 7.6) and 40 μL added to all 96 wells (final PARP-1 concentration in the assay is ~1 ng/μL). The plate is sealed and shaken at RT for 15 min. Following this, 10 μL of positive reaction mix (0.2 ng/μL of double-stranded oligonucleotide [M3/M4] DNA per well, 5 μM of NAD+ final assay concentration, and 0.075 μCi 3H-NAD+ per well) is added to the appropriate wells (columns 1-11). The negative reaction mix, lacking the DNA oligonucleotide, is added to column 12 (with the mean negative control value used as the background). The plate is resealed and shaken for a further 60 min at RT to allow the reaction to continue. Then, 50 μL of ice-cold acetic acid (30%) is added to each well to stop the reaction, and the plate is sealed and shaken for a further 60 min at RT. Tritiated signal bound to the FlashPlate is then determined in counts per minute (CPM) using the TopCount plate reader.

Cell Assay: The cytotoxicity of Olaparib is measured by clonogenic assay. Olaparib is dissolved in DMSO and diluted by culture media before use. The cells (Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D) are seeded in six well plates and left to attach overnight. Then Olaparib is added at various concentrations and the cells are incubated for 7-14 days. After that the surviving colonies are counted for calculating the IC50.

In Vivo

Combining with temozolomide, Olaparib (10 mg/kg, p.o.) significantly suppresses tumor growth in SW620 xenografts. Olaparib shows great response to Brca1-/-;p53-/- mammary tumors (50 mg/kg i.p. per day), while no responses to HR-deficient Ecad-/-;p53-/- mammary tumors. Olaparib even does not show dose-limiting toxicity in tumor-bearing mice. Olaparib has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, Olaparib shows selectively inhibition to ATM (Ataxia Telangiectasia Mutated)-deficient tumor cells, which indicates to be a potential agent for treating ATM mutant lymphoid tumors.

Animal model

Granta-519–engrafted NOD/SCID mice

Formulation & Dosage

Dissolved in 50 mg/mL stocks in DMSO with 10% 2-hydroxyl-propyl-β-cyclodextrine/PBS; 50 mg/kg; i.p. injection

References

J Med Chem. 2008 Oct 23;51(20):6581-91; Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84; Blood. 2010 Nov 25;116(22):4578-87.

CAS NO:	763113-22-0
规格:	≥98%

包装	价格(元)
100mg	电议
250mg	电议
500mg	电议
1g	电议
2g	电议
5g	电议