912444-00-9 Usage
Description
2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benimidazole-4-carboxamide, also known as Veliparib (ABT-888), is a potent, orally bioavailable PARP-1/-2 inhibitor. It is a benzimidazole derivative with a carbamoyl group at C-4 and a (2R)-2-methylpyrrolidin-2-yl moiety at C-2. Veliparib is a promising anti-cancer drug that acts by blocking the protein PARP, which prevents the repair of DNA damage in cancer cells, potentially making them more susceptible to anticancer treatments. It is an off-white solid.
Uses
Used in Oncology:
2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benimidazole-4-carboxamide is used as a PARP inhibitor for its potential anti-cancer properties. It is being investigated for the treatment of various types of cancer, including squamous and non-squamous non-small cell lung cancer, BRCA breast cancer, triple-negative breast cancer, and ovarian cancer. By inhibiting PARP, Veliparib (ABT-888) enhances the effectiveness of DNA damaging agents and may improve the outcomes of cancer treatments.
Used in Drug Development:
In the field of drug development, 2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benimidazole-4-carboxamide is used as a research compound for the development of new anti-cancer drugs. Its potent inhibitory effects on PARP-1/-2 make it a valuable candidate for further investigation and potential incorporation into novel therapeutic strategies for cancer treatment.
Biological activity
Veliparib (ABT-888) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Phase 3.
In vitro
Veliparib (ABT-888) is a potential anti-cancer drug acting as a PARP inhibitor，which inhibits PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays，respectively.ABT-888 reduces clonogenic survival and inhibits DNA repair in H460 cells. ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells.
In vivo
ABT-888 inhibits PARP in B16F10 and 9L xenograft models, thus enhancing the anticancer activity of temozolomide. The Combined with other cytotoxic agents, ABT-888 shows strong antitumor effect in MX-1 xenograft model. ABT-888 reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg according to the the size of tumors in A375 and Colo829 xenograft models.
Features
ABT-888 enhances the effectiveness of common cancer treatments, such as radiation therapy and alkylating agents.
References
https://www.abbvie.com/our-science/pipeline/veliparib.html
https://en.wikipedia.org/wiki/Veliparib
Biological Activity
abt-888, also named as veliparib, is poly (adp-ribose) polymerase (parp) inhibitor and has demonstrated excellent in vivo efficacy in a broad spectrum of preclinical tumor models in combination with a variety of cytotoxic agents. parp is involved in dna repair and elevated parp levels can result in resistance to cytotoxic chemotherapy and radiation. so, parp inhibitors hold promise as chemotherapy and radiation sensitizers. abt-888 is also active on microsatellite instability (msi) cell lines harboring mutations in both mre11 and rad50 genes compared to microsatellite stable (mss) cell lines (wild-type for both genes).shivaani kummar, robert kinders, martin e. gutierrez, larry rubinstein, ralph e. parchment, lawrence r. phillips, jiuping ji, anne monks, jennifer a. low, alice chen, anthony j. murgo, jerry collins, seth m. steinberg, helen eliopoulos, vincent l. giranda, gary gordon, lee helman, robert wiltrout, joseph e. tomaszewski and james h. doroshow. phase 0
Check Digit Verification of cas no
The CAS Registry Mumber 912444-00-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,1,2,4,4 and 4 respectively; the second part has 2 digits, 0 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 912444-00:
(8*9)+(7*1)+(6*2)+(5*4)+(4*4)+(3*4)+(2*0)+(1*0)=139
139 % 10 = 9
So 912444-00-9 is a valid CAS Registry Number.
InChI:InChI=1/C13H16N4O/c1-13(6-3-7-15-13)12-16-9-5-2-4-8(11(14)18)10(9)17-12/h2,4-5,15H,3,6-7H2,1H3,(H2,14,18)(H,16,17)/t13-/m1/s1
912444-00-9Relevant articles and documents
Preparation method of veliparib
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, (2020/08/12)
The invention discloses a preparation method of veliparib, which comprises the following steps: by using readily available L-alanine ethyl ester as a raw material, carrying out imidization, cyclization reduction and hydrolysis reaction to obtain a key chiral intermediate that is (R)-2-methylpyrrolidine-2-carboxylic acid, and carrying out one-step condensation on the intermediate to obtain the target compound veliparib. The method has the characteristics of easily available raw materials, mild conditions, simple process, safety, environmental protection and the like, and is suitable for industrial production.
Method for preparing (R)-2-(2-methylpyrrolidine-2-yl)-1H-benzimidazole-4-carboxamide
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Paragraph 0040-0050, (2017/03/17)
The invention relates to a method for preparing (R)-2-(2-methylpyrrolidine-2-yl)-1H-benzimidazole-4-carboxamide. The method has the advantages of avoiding of trifluoroacetic acid and other strong acids, simplification of present preparation technologies, pollution reduction, cost reduction, and improvement of the purity and the yield of the above product.
2-{(R)-2-METHYLPYRROLIDIN-2-YL)-1H-BENZIMIDAZOLE-4-CARBOXAMIDE CRYSTALLINE FORM 2
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Page/Page column 5-6, (2009/04/24)
2-((R)-2-Methylpyrrolidin-2-yl)- I H-benzimidazole-4-carboxamide Crystalline Form 2, ways to make it, compositions comprising it and made using it, and methods of treating patients having disease using it are disclosed.
