Synonym
AZD5305; AZD-5305; AZD 5305; Saruparib
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
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
More Info
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.
Biological target:
PARP inhibitor.
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
41.7 |
102.51 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
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 |
Formulation protocol:
TBD
1: Herencia-Ropero A, Llop-Guevara A, Staniszewska AD, Domènech-Vivó J, García-
Galea E, Moles-Fernández A, Pedretti F, Domènech H, Rodríguez O, Guzmán M,
Arenas EJ, Verdaguer H, Calero-Nieto FJ, Talbot S, Tobalina L, Leo E, Lau A,
Nuciforo P, Dienstmann R, Macarulla T, Arribas J, Díez O, Gutiérrez-Enríquez S,
Forment JV, O'Connor MJ, Albertella M, Balmaña J, Serra V. The PARP1 selective
inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in
patient-derived BRCA1/2-associated cancer models. Genome Med. 2024 Aug
26;16(1):107. doi: 10.1186/s13073-024-01370-z. PMID: 39187844; PMCID:
PMC11348616.
2: Stojanovic P, Luger K, Rudolph J. Slow Dissociation from the PARP1-HPF1
Complex Drives Inhibitor Potency. Biochemistry. 2023 Aug 15;62(16):2382-2390.
doi: 10.1021/acs.biochem.3c00243. Epub 2023 Aug 2. PMID: 37531469; PMCID:
PMC10433523.
