BRD-K98645985, a 12-membered macrolactam, is a novel and potent BAF (mammalian SWI/SNF) transcriptional repression inhibitor with an EC50 of ~2.37 µM. As a BAF (Brg/Brahma-associated factors) transcriptional repression inhibitor, BRD-K98645985 binds ARID1A-specific BAF complexes, prevents nucleosomal positioning, and potently reverses HIV-1 latency, and without T cell activation or toxicity.

Physicochemical Properties

Molecular Formula	C₃₃H₄₃N₅O₄
Molecular Weight	573.73
Exact Mass	573.33
Elemental Analysis	C, 69.08; H, 7.55; N, 12.21; O, 11.15
CAS #	1357647-78-9
Related CAS #	1357647-78-9;
PubChem CID	54633693
Appearance	White to light brown solid powder
LogP	4.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	42
Complexity	850
Defined Atom Stereocenter Count	3
SMILES	C[C@H]1CN([C@H](COC2=C(C=C(C=C2)NC(=O)NC(C)C)C(=O)N(C[C@@H]1OC)C)C)CC3=CC=C(C=C3)C4=CC=CC=N4
InChi Key	DZGZFXRKNSZUSK-MKGJDZFWSA-N
InChi Code	InChI=1S/C33H43N5O4/c1-22(2)35-33(40)36-27-14-15-30-28(17-27)32(39)37(5)20-31(41-6)23(3)18-38(24(4)21-42-30)19-25-10-12-26(13-11-25)29-9-7-8-16-34-29/h7-17,22-24,31H,18-21H2,1-6H3,(H2,35,36,40)/t23-,24-,31-/m0/s1
Chemical Name	1-[(4S,7S,8R)-8-methoxy-4,7,10-trimethyl-11-oxo-5-[(4-pyridin-2-ylphenyl)methyl]-2-oxa-5,10-diazabicyclo[10.4.0]hexadeca-1(12),13,15-trien-14-yl]-3-propan-2-ylurea
Synonyms	BRDK98645985 BRD K98645985
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	BAF transcriptional repression:2.37 μM (EC50); HIV-1
ln Vitro	Treatment with 30 μM BRD-K98645985 for 18 hours resulted in a 5-fold increase in Bmi1, a 2.6-fold increase in Ring1, and a 3.3-fold drop in Fgf4 [1]. In a model of J-Lat T cells, BRD-K98645985 therapy demonstrates concentration-dependent latency reversal. For better reservoir targeting, BRD-K98645985 can be utilized in conjunction with other LRAs [1].
References	[1]. Small Molecule Targeting of Specific BAF (mSWI/SNF) Complexes for HIV Latency Reversal. Cell Chem Biol. 2018 Dec 20;25(12):1443-1455.e14.
Additional Infomation	1-[(4S,7S,8R)-8-methoxy-4,7,10-trimethyl-11-oxo-5-[[4-(2-pyridinyl)phenyl]methyl]-2-oxa-5,10-diazabicyclo[10.4.0]hexadeca-1(12),13,15-trien-14-yl]-3-propan-2-ylurea is an azamacrocycle and a lactam.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~435.75 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.63 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 20.8 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: 2.08 mg/mL (3.63 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO 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: ≥ 2.08 mg/mL (3.63 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 20.8 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	1.7430 mL	8.7149 mL	17.4298 mL
	5 mM	0.3486 mL	1.7430 mL	3.4860 mL
	10 mM	0.1743 mL	0.8715 mL	1.7430 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.