ARD-266

Size	Price	Stock	Quantity
--	$--	In stock

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

IUPACName

(2S,4R)-N-[(1S)-3-[4-[2-[4-[[(1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl]ethynyl]piperidin-1-yl]-3-oxo-1-phenylpropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide

Synonyms

2-Pyrrolidinecarboxamide, N-[(1S)-3-[4-[2-[4-[[[trans-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]amino]carbonyl]phenyl]ethynyl]-1-piperidinyl]-3-oxo-1-phenylpropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-5-isoxazolyl)-1-oxobutyl]-, (2S,4R)-; (2S,4R)-N-((S)-3-(4-((4-(((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)carbamoyl)phenyl)ethynyl)piperidin-1-yl)-3-oxo-1-phenylpropyl)-4-hydroxy-1-((R)-3-methyl-2-(3-methylisoxazol-5-yl)butanoyl)pyrrolidine-2-carboxamide; (2S,4R)-N-[(1S)-3-[4-[2-[4-[[[trans-3-(3-Chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]amino]carbonyl]phenyl]ethynyl]-1-piperidinyl]-3-oxo-1-phenylpropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-5-isoxazolyl)-1-oxobutyl]-2-pyrrolidinecarboxamide

Boiling Point

1095.6±65.0°C at 760 Torr

Density

1.31±0.1 g/cm3

InChI Key

RTNONCBKGZNCJS-LJLQSONVSA-N

InChI

InChI=1S/C52H59ClN6O7/c1-31(2)45(43-25-32(3)57-66-43)48(64)59-30-38(60)26-42(59)47(63)55-41(35-11-9-8-10-12-35)28-44(61)58-23-21-34(22-24-58)14-13-33-15-17-36(18-16-33)46(62)56-49-51(4,5)50(52(49,6)7)65-39-20-19-37(29-54)40(53)27-39/h8-12,15-20,25,27,31,34,38,41-42,45,49-50,60H,21-24,26,28,30H2,1-7H3,(H,55,63)(H,56,62)/t38-,41+,42+,45-,49-,50-/m1/s1

Canonical SMILES

N#CC1=CC=C(OC2C(C)(C)C(NC(=O)C3=CC=C(C#CC4CCN(C(=O)CC(NC(=O)C5N(C(=O)C(C=6ON=C(C6)C)C(C)C)CC(O)C5)C=7C=CC=CC7)CC4)C=C3)C2(C)C)C=C1Cl

1. Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands

Lijie Zhao, Jeanne Stuckey, Weiguo Xiang, Krishnapriya Chinnaswamy, Xin Han, Shaomeng Wang, Mi Wang, Bukeyan Miao, Chao-Yie Yang, Tianfeng Xu, Chong Qin J Med Chem . 2019 Dec 26;62(24):11218-11231. doi: 10.1021/acs.jmedchem.9b01393.

Androgen receptor (AR) is a validated therapeutic target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We report herein our design, synthesis, and biological characterization of highly potent small-molecule proteolysis targeting chimera (PROTAC) AR degraders using a potent AR antagonist and E3 ligase ligands with weak binding affinities to VHL protein. Our study resulted in the discovery of11(ARD-266), which effectively induces degradation of AR protein in AR-positive (AR+) LNCaP, VCaP, and 22Rv1 prostate cancer cell lines with DC50values of 0.2-1 nM. ARD-266 is capable of reducing the AR protein level by >95% in these AR+ prostate cancer cell lines and effectively reduces AR-regulated gene expression suppression. For the first time, we demonstrated that an E3 ligand with micromolar binding affinity to its E3 ligase complex can be successfully employed for the design of highly potent and efficient PROTAC degraders and this finding may have a significant implication for the field of PROTAC research.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂