WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 556018
Description: AZD5305 is a potent, selective and oral active PARP inhibitor. AZD5305 is a highly potent inhibitor of PARP1, with significant PARP1-DNA trapping activity, no PARP2-activity, nor binding activity to any other members of the PARP family. AZD5305 has excellent secondary pharmacology and physicochemical properties as well as high oral bioavailability in preclinical species.
MedKoo Cat#: 556018
Chemical Formula: C22H26N6O2
Exact Mass: 406.2117
Molecular Weight: 406.49
Elemental Analysis: C, 65.01; H, 6.45; N, 20.68; O, 7.87
Synonym: AZD5305; AZD-5305; AZD 5305;
IUPAC/Chemical Name: 5-(4-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)piperazin-1-yl)-N-methylpicolinamide
InChi Key: WQAVGRAETZEADU-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H26N6O2/c1-3-16-11-19-20(26-21(16)29)10-15(12-24-19)14-27-6-8-28(9-7-27)17-4-5-18(25-13-17)22(30)23-2/h4-5,10-13H,3,6-9,14H2,1-2H3,(H,23,30)(H,26,29)
SMILES Code: O=C(C1=NC=C(N2CCN(CC3=CC(N4)=C(N=C3)C=C(CC)C4=O)CC2)C=C1)NC
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||PARP inhibitor.|
|In vitro activity:||TBD|
|In vivo activity:||TBD|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 406.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||TBD|
|In vivo protocol:||TBD|
In vitro, AZD5305 inhibits growth selectively in cell lines with deficiencies in DNA repair pathways, with IC50s in the single-digit nM range, while having no or minimal growth inhibitory effects in other cells (IC50s >10μM). The difference observed between the effects on DNA repair deficient and proficient cell lines is unprecedented with PARP inhibitors and indicates the great potential for AZD5305 to demonstrate an improved therapeutic index in the clinic. Treatments of xenografts and PDX models with AZD5305 at doses ≥ 0.1 mg/kg QD, compared to olaparib 100 mg/kg QD, resulted in greater depth of tumor regressions, as well as significantly longer duration of regressions following cessation of dosing.
Overall, AZD5305 is a next generation PARP inhibitor and trapper, with enhanced anticancer efficacy and an improved safety profile in preclinical models compared to other PARP inhibitors. These features make AZD5305 an exciting and unique clinical candidate, with multiple clinical options as monotherapy and in combination. AZD5305 is in Ph1 clinical trials.