ARCC 4, a PROTAC.

ARCC 4 is a PROTAC, acting as an androgen receptor degrader. 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.

Product information

CAS Number: 1973403-00-7

Molecular Weight: 1024.18

Formula: C53H56F3N7O7S2

Synonym:

ARCC-4

ARCC4

ARCC-4 hydrate

ARCC 4

Related CAS Number:

1973403-00-7 (free base)

Chemical Name: (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]acetamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Smiles: CC(C)(C)[C@H](NC(=O)COCCCCOC1C=CC(=CC=1)C1C=CC(=CC=1)N1C(=S)N(C(=O)C1(C)C)C1=CC(=C(C=C1)C#N)C(F)(F)F)C(=O)N1C[C@H](O)C[C@H]1C(=O)NCC1C=CC(=CC=1)C1SC=NC=1C

InChiKey: DUPAJELXESPTNF-PPZGWQTASA-N

InChi: InChI=1S/C53H56F3N7O7S2/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)/t40-,43+,46-/m1/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

ARCC-4 induces apoptosis and inhibiting proliferation of AR-amplified prostate cancer cells. ARCC-4 enhances protein-protein interactions between AR and VHL, thereby promoting the association of the trimeric complex. ARCC-4 (0.1-10, 000 nM; 20 hours) potently degrades AR with a D50 of 5 nM and Dmax of over 95%. ARCC-4 (100 nM; 12 hours) shows near complete AR degradation (>98%) in prostate cancer cells. ARCC-4 selectively degrades AR via the proteasome but not PR-A or PR-B suppression. ARCC-4 shows efficacy against clinically relevant AR mutations. ARCC-4 maintains activity despite elevated androgen levels.

References:

1. Salami J, Alabi S, Willard RR, Vitale NJ, Wang J, Dong H, Jin M, McDonnell DP, Crew AP, Neklesa TK, Crews CM. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance. Commun Biol. 2018 Aug 2;1:100. doi: 10.1038/s42003-018-0105-8. eCollection 2018. PubMed PMID: 30271980; PubMed Central PMCID: PMC6123676.

Products are for research use only. Not for human use.