Pamiparib (BGB-290) - 99%, high purity , Poly [ADP-ribose] polymerase 2 inhibitor, CAS No.1446261-44-4, Poly [ADP-ribose] polymerase 2 inhibitor

Item Number

P414075

• Synonyms: (10aR)-2-Fluoro-10a-methyl-5,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta(1,2,3,4-def)cyclopenta(a)fluoren-4(7H)-one | A884779 | Pamiparib [INN] | BP180190 | DENYZIUJOTUUNY-MRXNPFEDSA-N | Pamiparib (BGB-290) | Q2701649 | Pamiparib free base | SCHE
• Specifications & Purity: Moligand™, ≥99%
• Biochemical and Physiological Mechanisms: Pamiparib (BGB-290) is a potent and selective inhibitor of PARP1 and PARP2 with IC50 values of 0.83 and 0.11 nM, respectively in biochemical assays. It shows high selectivity over other PARP enzymes.
• Storage Temp: Store at -20°C
• Shipped In: Ice chest + Ice pads
• Grade: Moligand™
• Action Type: INHIBITOR
• Mechanism of action: Poly [ADP-ribose] polymerase 2 inhibitor

Product Description

Information

Pamiparib (BGB-290) is a potent and selective inhibitor ofPARP1andPARP2with IC50 values of 0.83 and 0.11 nM, respectively in biochemical assays. It shows high selectivity over other PARP enzymes.

Targets

PARP2 (Cell-free assay); PARP1 (Cell-free assay) 0.11 nM; 0.83 nM

In vitro

BGB-290 shows potent DNA-trapping activity with IC50 of 13 nM. In the cellular assays, BGB-290 inhibits intracellular PAR formation with an IC50 of 0.24 nM.

In vivo

Oral administration of BGB-290 results in time-dependent and dose-dependent inhibition of PARylation in MDA-MB-436 (BRCA1 mutant) breast cancer xenograft, correlating well with the tumor drug concentrations. BGB-290 has also demonstrated good combination activity with chemotherapeutics in patient biopsy derived SCLC models. BGB-290 has significant brain penetration in C57 mice. The drug exposure in brain vs. that in plasma was close to 20% after oral administration of BGB-290.

Product Application：

Pamiparib, an investigational Poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development, demonstrates excellent selectivity for both PARP1 and PARP2, and superb anti-proliferation activities in tumor cell lines with BRCA1/2 mutations or HR pathway deficiency (HRD). Pamiparib has good bioavailability and is 16-fold more potent than olaparib in an efficacy study using BRCA1 mutated MDA-MB-436 breast cancer xenograft model. Pamiparib also shows strong anti-tumor synergy with temozolomide (TMZ), a DNA alkylating agent used to treat brain tumors. Compared to other PARP inhibitors, pamiparib demonstrated improved penetration across the blood brain barrier (BBB) in mice. Oral administration of pamiparib at a dose as low as 3 mg/kg is sufficient to abrogate PARylation in brain tumor tissues. In SCLC-derived, TMZ-resistant H209 intracranial xenograft model, combination of pamiparib with TMZ overcomes its resistance and shows significant tumor inhibitory effects and prolonged life span.