ZXH-4-130 TFA

• CAT Number: I045358
• CAS Number: 2711006-67-4
• Molecular Formula: C48H59F3N6O11S
• Molecular Weight: 985.08
• Purity: ≥95%
• Synonyms: (2S,4R)-1-[(2S)-2-[11-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyundecanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid
• InChI: InChI=1S/C46H58N6O9S.C2HF3O2/c1-28-39(62-27-48-28)30-19-17-29(18-20-30)25-47-41(56)34-24-31(53)26-51(34)45(60)40(46(2,3)4)49-36(54)16-11-9-7-5-6-8-10-12-23-61-35-15-13-14-32-38(35)44(59)52(43(32)58)33-21-22-37(55)50-42(33)57;3-2(4,5)1(6)7/h13-15,17-20,27,31,33-34,40,53H,5-12,16,21-26H2,1-4H3,(H,47,56)(H,49,54)(H,50,55,57);(H,6,7)/t31-,33?,34+,40-;/m1./s1
• InChIKey: QKDOGOBHFHCHMX-YYRHATPXSA-N
• SMILES: CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CCCCCCCCCCOC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O)O.C(=O)(C(F)(F)F)O

ZXH-4-130 TFA is a highly potent and selective degrader of CRBN. ZXH-4-130 is a CRBN-VHL compound (hetero-PROTAC). ZXH-4-130 TFA induces ~80% CRBN degradation at 10 nM in MM1.S cells[1].
ZXH-4-130 (100 nM; 2 h pre-treatment; followed by 96-hour treatment with 1 μM of Pomalidomide) TFA prevents Pomalidomide (1 μM) cytotoxicity to a significant extent, ZXH-4-130 TFA has statistically significant amounts of prevention[1].
ZXH-4-130 TFA (pretreatment with 50 nM) rescues GSPT1 degradation induced by CC-885 in
MM1.S cells[1].
ZXH-4-130 (100 nM; 2 h pre-treatment; followed by 6 h treatment with THAL-SNS-032)TFA induces nearly complete CRBN degradation, but THAL-SNS-032’s activity against CDK9 is only partially prevented[1].

Reference

[1]. Chelsea E Powell, et al. Selective degradation-inducing probes for studying cereblon (CRBN) biology. RSC Med Chem. 2021 Jul 6;12(8):1381-1390.
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