Rucaparib Camsylate

Rucaparib Camsylate is an inhibitor of PARP with a Ki of 1.4 nM for PARP1. Rucaparib Camsylate also shows binding affinity to eight other PARP domains.

Product information

CAS Number: 1859053-21-6

Molecular Weight: 555.66

Formula: C29H34FN3O5S

Chemical Name: 6-fluoro-2-{4-[(methylamino)methyl]phenyl}-3,10-diazatricyclo[6.4.1.0⁴,¹³]trideca-1,4,6,8(13)-tetraen-9-one; [(1S,4R)-4-hydrogenio-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl]methanesulfonic acid

Smiles: CC1(C)[C@H]2CC(=O)[C@]1(CS(O)(=O)=O)CC2.CNCC1C=CC(=CC=1)C1NC2=CC(F)=CC3=C2C=1CCNC3=O

InChiKey: INBJJAFXHQQSRW-STOWLHSFSA-N

InChi: InChI=1S/C19H18FN3O.C10H16O4S/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15;1-9(2)7-3-4-10(9,8(11)5-7)6-15(12,13)14/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);7H,3-6H2,1-2H3,(H,12,13,14)/t;7-,10-/m.1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 83.33 mg/mL (149.97 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Rucaparib is the most potent PARP inhibitor in enzyme assays (Ki, 1.4 nM), and a possible N-demethylation metabolite of AG14644. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.

In Vivo:

Rucaparib and AG14584 significantly (P < 0.05) increases temozolomide toxicity. Rucaparib (1 mg/kg) significantly increases temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) results in a 50% increase in the temozolomide-induced tumor growth delay. Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.

References:

1. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.
2. Hunter JE, et al. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.
3. Daniel RA, et al. Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699. Br J Cancer, 2010, 103(10), 1588-1596.

Products are for research use only. Not for human use.