CUR-61414

• CAT Number: R009173
• CAS Number: 334998-36-6
• Molecular Formula: C31H42N4O5
• Molecular Weight: 550.7
• Purity: ≥95%
• Target: Hedgehog
• Solubility: Soluble in DMSO
• Storage: Store at -20°C
• IUPAC Name: N-[(3S,5S)-1-(1,3-benzodioxol-5-ylmethyl)-5-(piperazine-1-carbonyl)pyrrolidin-3-yl]-N-[(3-methoxyphenyl)methyl]-3,3-dimethylbutanamide
• InChI: InChI=1S/C31H42N4O5/c1-31(2,3)17-29(36)35(19-22-6-5-7-25(14-22)38-4)24-16-26(30(37)33-12-10-32-11-13-33)34(20-24)18-23-8-9-27-28(15-23)40-21-39-27/h5-9,14-15,24,26,32H,10-13,16-21H2,1-4H3/t24-,26-/m0/s1
• InChIKey: WPHXYKUPFJRJDK-AHWVRZQESA-N
• SMILES: CC(C)(C)CC(=O)N(CC1=CC(=CC=C1)OC)C2CC(N(C2)CC3=CC4=C(C=C3)OCO4)C(=O)N5CCNCC5

CUR-61414, also known as G-024856 and G-856, is a smoothened receptor antagonist potentially for the treatment of basal cell carcinoma. CUR61414 significantly inhibited skin Hedgehog signaling, blocked the induction of hair follicle anagen, and shrank existing basal cell carcinomas. CUR61414 can suppress proliferation and induce apoptosis of basaloid nests in the basal cell carcinoma model systems, whereas having no effect on normal skin cells.

Reference

1:J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Mar 1;887-888:85-92. doi: 10.1016/j.jchromb.2012.01.016. Epub 2012 Jan 25. Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of G-856 (Cur-61414) in human plasma using semi-automated solid phase extraction.Shin YG,Murakami SC,Buonarati MH,Dean B,Hop CE, PMID: 22317788 DOI: 10.1016/j.jchromb.2012.01.016 Abstract: A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of G-856 in human plasma to support clinical development. The method consisted of a solid phase extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray for analysis. d₈-G-856 was used as the internal standard. A linear regression (weighted 1/concentration²) was used to fit calibration curves over the concentration range of 5.00-2000 pg/mL for G-856. There were no significant endogenous interference components in the multiple lots of blank human plasma tested. The accuracy (%Acc) at the lower limit of quantitation (LLOQ) was 98.2% with a precision (%CV) of 5.38%. For quality control samples at 15.0, 800, and 1600 pg/mL, the inter-day %CV was ≤ 5.03%. Inter-day %Acc ranged from 96.9 to 99.3%. G-856 was stable in human plasma for 184 days at -20 °C and -70 °C storage. G-856 was stable in human plasma at room temperature for up to 16 h and through four freeze/thaw cycles. This validated LC-MS/MS method for determination of G-856 was used to support Phase 1 clinical studies.Copyright © 2012 Elsevier B.V. All rights reserved.