Veliparib 2HCl (ABT-888)

SKU: orb1306469

Description

Veliparib dihydrochloride is a potent and selective PARP1/2 inhibitor with Ki values of 5.2 nM and 2.9 nM, respectively, while showing no activity against SIRT2. This small molecule is widely used in cancer research, particularly in studying synthetic lethality and chemo/radiosensitization in both cellular and animal models.

Research Area

Cell Biology, Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 912445-05-7
• MW: 317.2
• Purity: >98%
• Formula: C₁₃H₁₆N₄O • 2HCl
• SMILES: Cl.Cl.C[C@@]1(CCCN1)c1nc2c(cccc2[nH]1)C(N)=O
• Target: PARP
• Solubility: Soluble in DMSO (up to 30 mg/ml) or in Water (up to 40 mg/ml).

Bioactivity

• Target IC50:
  PARP2:2.9 nM(Ki)|PARP1:5.2 nM (Ki)
• In Vivo:
  Veliparib exhibits an oral bioavailability ranging from 56% to 92% across different species, including mice, SD rats, beagle dogs, and cynomolgus monkeys. At a dosage of 25 mg/kg (i.p.), it enhances tumor growth delay in NCI-H460 xenograft models and, when combined with radiation, decreases tumor vessel formation. Additionally, Veliparib significantly reduces intratumor PAR levels by over 95% at dosages of 3 and 12.5 mg/kg in A375 and Colo829 xenograft models, with this suppression sustained over time.
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• In Vitro:
  Veliparib demonstrates inactivity towards SIRT2 at concentrations greater than 5 μM and exhibits potent inhibition of PARP activity, with an EC50 of 2 nM in C41 cells. It effectively reduces PAR levels in H460 cells, regardless of irradiation status, and significantly impairs clonogenic survival by hindering DNA repair via PARP-1 inhibition. Additionally, when used in conjunction with radiation, Veliparib promotes apoptosis and autophagy in H460 cells. Its ability to inhibit PARP activity extends to H1299, DU145, and 22RV1 cells, a process not influenced by p53 function. At a concentration of 10 μM, Veliparib diminishes the surviving fraction in clonogenic H1299 cells by 43%, enhancing radiosensitivity, particularly in oxygen-rich environments. Furthermore, it reduces the surviving fraction in H1299, DU145, and 22RV1 cells under hypoxic-irradiated conditions, confirming its role in sensitizing cancer cells to radiation by targeting PARP-dependent mechanisms.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ABT-888

Compound Identifiers

PubChem CID

45480520