SNIPER(BRD)-1 is a novel and potent BRD4 degrader consisting of an IAP antagonist LCL-161 derivative and a BET inhibitor, (+)-JQ-1, connected via a linker. It induces the degradation of BRD4 via the ubiquitin-proteasome pathway, also degrades cIAP1 , cIAP2 and XIAP with IC50s of 6.8 nM, 17 nM, and 49nM, respectively.

Physicochemical Properties

Molecular Formula	C53H66CLN9O8S2
Molecular Weight	1056.72964906693
Exact Mass	1055.416
CAS #	2095244-54-3
PubChem CID	138377573
Appearance	Off-white to light yellow solid powder
LogP	6.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	15
Rotatable Bond Count	24
Heavy Atom Count	73
Complexity	1830
Defined Atom Stereocenter Count	4
SMILES	ClC1C=CC(=CC=1)C1C2C(C)=C(C)SC=2N2C(C)=NN=C2[C@H](CC(NCCOCCOCCOCCOC2=CC=CC(=C2)C(C2=CSC([C@@H]3CCCN3C([C@H](C3CCCCC3)NC([C@H](C)NC)=O)=O)=N2)=O)=O)N=1
InChi Key	FVDSZRCRCFMYQV-CDYWKMCDSA-N
InChi Code	InChI=1S/C53H66ClN9O8S2/c1-32-34(3)73-53-45(32)46(37-16-18-39(54)19-17-37)57-41(49-61-60-35(4)63(49)53)30-44(64)56-20-22-68-23-24-69-25-26-70-27-28-71-40-14-9-13-38(29-40)48(65)42-31-72-51(58-42)43-15-10-21-62(43)52(67)47(36-11-7-6-8-12-36)59-50(66)33(2)55-5/h9,13-14,16-19,29,31,33,36,41,43,47,55H,6-8,10-12,15,20-28,30H2,1-5H3,(H,56,64)(H,59,66)/t33-,41-,43-,47-/m0/s1
Chemical Name	(2S)-N-[(1S)-2-[(2S)-2-[4-[3-[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]benzoyl]-1,3-thiazol-2-yl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]-2-(methylamino)propanamide
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.
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

References

[1]. Different Degradation Mechanisms of Inhibitor of Apoptosis Proteins (IAPs) by the Specific and Nongenetic IAP-Dependent Protein Eraser (SNIPER). Chem Pharm Bull (Tokyo). 2019 Mar 1;67(3):203-209.

Solubility Data

Solubility (In Vitro)

DMSO : ~66.67 mg/mL (~63.09 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.37 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 25.0 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	0.9463 mL	4.7316 mL	9.4632 mL
	5 mM	0.1893 mL	0.9463 mL	1.8926 mL
	10 mM	0.0946 mL	0.4732 mL	0.9463 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.