MDK7526 HCl

• CAT Number: I011953
• CAS Number: 1448189-80-7
• Molecular Formula: C22H31ClN4O3S
• Molecular Weight: 467.025
• Purity: ≥95%
• Synonyms: VHL Ligand 1 (hydrochloride); Protein degrader 1 hydrochloride; MDK7526 HCl; MDK7526; MDK-7526; MDK 7526.;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride
• Solubility: Soluble in DMSO
• Storage: Store at 0-8 °C
• InChI: InChI=1S/C22H30N4O3S.ClH/c1-13-18(30-12-25-13)15-7-5-14(6-8-15)10-24-20(28)17-9-16(27)11-26(17)21(29)19(23)22(2,3)4;/h5-8,12,16-17,19,27H,9-11,23H2,1-4H3,(H,24,28);1H/t16-,17+,19-;/m1./s1
• InChIKey: JYRTWGCWUBURGU-MSSRUXLCSA-N
• SMILES: O=C([C@H]1N(C([C@@H](N)C(C)(C)C)=O)C[C@H](O)C1)NCC2=CC=C(C3=C(C)N=CS3)C=C2.[H]Cl

MDK7526 HCl (CAT: I011953) is a potent and selective protein degrader, also known as Protein degrader 1 or VHL Ligand 1. It is specifically designed to target and degrade the androgen receptor (AR). MDK7526 HCl binds to the AR and recruits the ubiquitin ligase VHL (von Hippel-Lindau) complex, leading to the ubiquitination and subsequent degradation of the AR protein. By promoting the degradation of AR, MDK7526 HCl can effectively inhibit AR-mediated signaling pathways, making it a potential therapeutic option for diseases such as prostate cancer, where the AR pathway plays a critical role.

Reference

1. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7124-9. doi:
10.1073/pnas.1521738113. Epub 2016 Jun 6.
PROTAC-induced BET protein degradation as a therapy for castration-resistant
prostate cancer.
Raina K(1), Lu J(1), Qian Y(1), Altieri M(1), Gordon D(1), Rossi AM(1), Wang
J(1), Chen X(1), Dong H(1), Siu K(1), Winkler JD(1), Crew AP(1), Crews CM(2),
Coleman KG(3).
Author information:
(1)Arvinas, LLC, New Haven, CT 06511;
(2)Department of Molecular, Cellular, and Developmental Biology, Yale University,
New Haven, CT 06520; Department of Chemistry, Yale University, New Haven, CT
06520; Department of Pharmacology, Yale University, New Haven, CT 06520.
(3)Arvinas, LLC, New Haven, CT 06511; .
Prostate cancer has the second highest incidence among cancers in men worldwide
and is the second leading cause of cancer deaths of men in the United States.
Although androgen deprivation can initially lead to remission, the disease often
progresses to castration-resistant prostate cancer (CRPC), which is still reliant
on androgen receptor (AR) signaling and is associated with a poor prognosis. Some
success against CRPC has been achieved by drugs that target AR signaling, but
secondary resistance invariably emerges, and new therapies are urgently needed.
Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have
shown growth-inhibitory activity in preclinical models of CRPC. Here, we
demonstrate that ARV-771, a small-molecule pan-BET degrader based on
proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically
improved efficacy in cellular models of CRPC as compared with BET inhibition.
Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR
levels and leads to tumor regression in a CRPC mouse xenograft model. This study
is, to our knowledge, the first to demonstrate efficacy with a small-molecule BET
degrader in a solid-tumor malignancy and potentially represents an important
therapeutic advance in the treatment of CRPC.