ZXH-4-130 TFA is an efficient and selective CRBN degradation agent. ZXH-4-130 is a CRBN-VHL compound (hetero-PROTAC). In MM1.S cells, ZXH-4-130 TFA induced approximately 80% CRBN degradation at 10 nM.

Physicochemical Properties

Molecular Formula	C48H59F3N6O11S
Molecular Weight	985.08
Exact Mass	984.391
CAS #	2711006-67-4
Related CAS #	ZXH-4-130;2711006-66-3
PubChem CID	162640901
Appearance	Off-white to gray solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	16
Rotatable Bond Count	20
Heavy Atom Count	69
Complexity	1700
Defined Atom Stereocenter Count	3
SMILES	N1=CSC(C2C=CC(=CC=2)CNC([C@@H]2C[C@H](CN2C(=O)[C@H](C(C)(C)C)NC(CCCCCCCCCCOC2=CC=CC3=C2C(=O)N(C2CCC(NC2=O)=O)C3=O)=O)O)=O)=C1C.OC(=O)C(F)(F)F
InChi Key	QKDOGOBHFHCHMX-YYRHATPXSA-N
InChi Code	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
Chemical Name	(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
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	VHL
ln Vitro	ZXH-4-130 TFA (100 nM; pretreatment for 2 hours; subsequent treatment with 1 μM pomalidomide for 96 hours) has a statistically significant preventative effect [1] that greatly inhibits the cytotoxicity of pomalidomide (1 μM). In MM1.S cells, ZXH-4-130 TFA (50 nM pretreatment) prevents GSPT1 degradation caused by CC-885 [1]. ZXH-4-130 (100 nM) TFA causes nearly total CRBN degradation, but only partially blocks THAL-SNS-032's activity on CDK9 [1]. This is followed by a 6-hour THAL-SNS-032 treatment.
References	[1]. Selective degradation-inducing probes for studying cereblon (CRBN) biology. RSC Med Chem. 2021 Jul 6;12(8):1381-1390.

Solubility Data

Solubility (In Vitro)

DMSO :~170 mg/mL (~172.57 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 4.25 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.0151 mL	5.0757 mL	10.1515 mL
	5 mM	0.2030 mL	1.0151 mL	2.0303 mL
	10 mM	0.1015 mL	0.5076 mL	1.0151 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.