MS417 is a selective inhibitor of BET-specific protein BRD4, which can bind to BRD4-BD1 and BRD4-BD2, with IC50s of 30, 46 nM and Kds of 36.1 and 25.4 nM respectively; MS417 has an inhibitory activity against CBP BRD. The selectivity is low, with IC50 of 32.7 μM.

Physicochemical Properties

Molecular Formula	C20H19CLN4O2S
Molecular Weight	414.908
Exact Mass	414.091
CAS #	916489-36-6
PubChem CID	59190723
Appearance	Light yellow to yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	596.8±60.0 °C at 760 mmHg
Flash Point	314.7±32.9 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.698
LogP	3.26
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	627
Defined Atom Stereocenter Count	1
SMILES	CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)OC)C4=CC=C(C=C4)Cl)C
InChi Key	GGRCIHACOIMRKY-HNNXBMFYSA-N
InChi Code	InChI=1S/C20H19ClN4O2S/c1-10-11(2)28-20-17(10)18(13-5-7-14(21)8-6-13)22-15(9-16(26)27-4)19-24-23-12(3)25(19)20/h5-8,15H,9H2,1-4H3/t15-/m0/s1
Chemical Name	methyl 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]acetate
Synonyms	MS 417; MS-417; MS417
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

ln Vitro	BET potential BRD4, MS417 binds to BRD4-BD1 and BRD4-BD2 with IC50 values of 30 and 46 nM, respectively, and Kd values of 36.1 and 25.4 nM. Its selectivity towards CBP BrD is weaker (IC50 = 32.7 μM). In human embryonic kidney 293T cells, TNFα-induced NF-κB activation is nearly entirely inhibited by MS417 at 1 μM. Additionally, MS417 p65 networked MS417 (1 μM) in HIV-infected RTEC is reduced. These results indicate that MS417 affects gene regulation in HIV-infected human renal tubular epithelial cells. Furthermore, MS417 suppresses NF-κB, which has an impact on chemokines and cytokines [1].
ln Vivo	In Tg26 mice, renal tubular injury, proteinuria, glomerular lymphoma, and inflammatory cell respiration are all markedly reduced when MS417 (0.08 mg/kg) is administered [1].
References	[1]. Down-regulation of NF-κB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. J Biol Chem. 2012 Aug 17;287(34):28840-51.
Additional Infomation	MS-417 is a member of the class of thienotriazolodiazepines that is the methyl ester of [(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid. A bromodomain and extra-terminal domain (BET)-specific inhibitor that belongs to a group of thienodiazepine-based compounds It is a thienotriazolodiazepine, a member of monochlorobenzenes and a methyl ester. It is an enantiomer of a MS-566.

Solubility Data

Solubility (In Vitro)

Ethanol : ~50 mg/mL (~120.51 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 (6.03 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in 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 EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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	2.4102 mL	12.0508 mL	24.1016 mL
	5 mM	0.4820 mL	2.4102 mL	4.8203 mL
	10 mM	0.2410 mL	1.2051 mL	2.4102 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.