ARCC-4

Size	Price	Stock	Quantity
--	$--	In stock

Size

Price

Stock

Quantity

$--

In stock

Purity

99%

Solubility

In DMSO: 200 mg/mL (195.28 mM; Need ultrasonic)

Storage

Powder, -20°C, 3 years; 4°C, 2 years; In solvent, -80°C, 6 months; -20°C, 1 month

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

(2S,4R)-1-[(2S)-2-[[2-[4-[4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]phenyl]phenoxy]butoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

ARCC-4; 1973403-00-7; (2S,4R)-1-((S)-2-(2-(4-((4'-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-[1,1'-biphenyl]-4-yl)oxy)butoxy)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide; CHEMBL4540528; SCHEMBL17946930; DUPAJELXESPTNF-PPZGWQTASA-N; AKOS040741162; MS-31874; HY-130492; CS-0108331; EN300-7526556; Z3482428589; O1-(ABM-14 ether), O4-(Methylcarboxamide with AHPC) Butanediol; (2S,4R)-1-[(2S)-2-(2-{4-[(4'-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-[1,1'-biphenyl]-4-yl)oxy]butoxy}acetamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide

InChI Key

NBHWEDHRTGEGEB-VKZLHUHRSA-N

InChI

InChI=1S/C53H56F3N7O7S2.H2O/c1-32-45(72-31-59-32)36-11-9-33(10-12-36)28-58-47(66)43-26-40(64)29-61(43)48(67)46(51(2,3)4)60-44(65)30-69-23-7-8-24-70-41-21-16-35(17-22-41)34-13-18-38(19-14-34)63-50(71)62(49(68)52(63,5)6)39-20-15-37(27-57)42(25-39)53(54,55)56;/h9-22,25,31,40,43,46,64H,7-8,23-24,26,28-30H2,1-6H3,(H,58,66)(H,60,65);1H2/t40-,43+,46-;/m1./s1

Canonical SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)COCCCCOC4=CC=C(C=C4)C5=CC=C(C=C5)N6C(=S)N(C(=O)C6(C)C)C7=CC(=C(C=C7)C#N)C(F)(F)F)O.O

1. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance

Taavi K Neklesa, Nick J Vitale, Jemilat Salami, Jing Wang, Ryan R Willard, Meizhong Jin, Donald P McDonnell, Craig M Crews, Shanique Alabi, Andrew P Crew, Hanqing Dong Commun Biol . 2018 Aug 2;1:100. doi: 10.1038/s42003-018-0105-8.

The androgen receptor is a major driver of prostate cancer and inhibition of its transcriptional activity using competitive antagonists, such as enzalutamide remains a frontline therapy for prostate cancer management. However, the majority of patients eventually develop drug resistance. We propose that targeting the androgen receptor for degradation via Proteolysis Targeting Chimeras (PROTACs) will be a better therapeutic strategy for targeting androgen receptor signaling in prostate cancer cells. Here we perform a head-to-head comparison between a currently approved androgen receptor antagonist enzalutamide, and its PROTAC derivative, ARCC-4, across different cellular models of prostate cancer drug resistance. ARCC-4 is a low-nanomolar androgen receptor degrader able to degrade about 95% of cellular androgen receptors. ARCC-4 inhibits prostate tumor cell proliferation, degrades clinically relevant androgen receptor point mutants and unlike enzalutamide, retains antiproliferative effect in a high androgen environment. Thus, ARCC-4 exemplifies how protein degradation can address the drug resistance hurdles of enzalutamide.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	0.98 mL	4.88 mL	9.76 mL
5 mM	0.2 mL	0.98 mL	1.95 mL
10 mM	0.1 mL	0.49 mL	0.98 mL
50 mM	0.02 mL	0.1 mL	0.2 mL

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂