ZXH-4-130 is an efficient and selective CRBN degrader. ZXH-4-130 is a CRBN-VHL compound (hetero-PROTAC).

Physicochemical Properties

Molecular Formula	C46H58N6O9S
Molecular Weight	871.052530765533
Exact Mass	870.398
CAS #	2711006-66-3
Related CAS #	ZXH-4-130 TFA;2711006-67-4
PubChem CID	156857734
Appearance	Typically exists as solid at room temperature
LogP	5.9
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	20
Heavy Atom Count	62
Complexity	1620
Defined Atom Stereocenter Count	3
SMILES	O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC(OCCCCCCCCCCC(=O)N[C@@H](C(C)(C)C)C(N3C[C@H](O)C[C@H]3C(=O)NCC3C=CC(C4=C(N=CS4)C)=CC=3)=O)=C12
InChi Key	CZQHTMJBCZCOMW-ZALOBHIXSA-N
InChi Code	InChI=1S/C46H58N6O9S/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/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)/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
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
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	Pomalidomide (1 μM) cytotoxicity is significantly prevented by ZXH-4-130 (100 nM; 2 h pre-treatments; followed by 96-hour treatment with 1 μM of Pomalidomide); ZXH-4-130 has statistically significant quantities of protection [1]. Prior to being exposed to CC-885, a substance that causes G1 to S phase transition protein 1 (GSPT1) degradation through CRBN E3 ligase recruitment, MM1.S cells are pre-treated for two hours with 50 nM of ZXH-4-130. ZXH-4-130 at 50 nM is used as a pretreatment to prevent GSPT1 degradation[1]. While THAL-SNS-032's action against CDK9 is only partially blocked, ZXH-4-130 (100 nM, 2 h pre-treatment, followed by 6 h treatment with THAL-SNS-032) produces nearly full CRBN degradation[1].
Cell Assay	Cell Viability Assay[1] Cell Types: MM1.S cells Tested Concentrations: 100 nM Incubation Duration: 2 h pre-treatments; followed by 96- hour treatment with 1 μM of Pomalidomide Experimental Results: Prevented Pomalidomide cytotoxicity to a significant extent, ZXH-4-130 has statistically significant amounts of prevention. Western Blot Analysis[1] Cell Types: MM1.S cells Tested Concentrations: 50 nM Incubation Duration: 2 h pretreatment with ZXH-4-130, followed by 4 h treatment with CC-885 Experimental Results: Rescued GSPT1 degradation.
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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.1480 mL	5.7402 mL	11.4804 mL
	5 mM	0.2296 mL	1.1480 mL	2.2961 mL
	10 mM	0.1148 mL	0.5740 mL	1.1480 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.