S65487 (VOB560) HCl is a potent and specific Bcl-2 inhibitor and the precursor of S55746. S65487 HCl is also active against BCL-2 mutations, such as G101V and D103Y. S65487 HCl has poor affinity for MCL-1, BFL-1 and BCL-XL. S65487 HCl causes apoptosis and has anti-neoplastic activity.

Physicochemical Properties

Molecular Formula	C41H41CLN6O4
Molecular Weight	717.255048513412
Exact Mass	752.264
CAS #	1644543-95-2
Related CAS #	S65487;1644600-79-2;S65487 sulfate;2416937-01-2
PubChem CID	117831262
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	53
Complexity	1300
Defined Atom Stereocenter Count	1
SMILES	ClC1=CC=C(C(=C1)C1=CC(C(N(C2C=CC(=CC=2)O)C2C=C(C#N)N(C)C=2C)=O)=C(C)N1C)C(N1CC2C=CC=CC=2C[C@H]1CN1CCOCC1)=O
InChi Key	KBXPYZATHHDCAQ-WAQYZQTGSA-N
InChi Code	InChI=1S/C41H41ClN6O4.ClH/c1-26-36(41(51)48(31-10-12-34(49)13-11-31)38-21-32(23-43)44(3)27(38)2)22-39(45(26)4)37-20-30(42)9-14-35(37)40(50)47-24-29-8-6-5-7-28(29)19-33(47)25-46-15-17-52-18-16-46;/h5-14,20-22,33,49H,15-19,24-25H2,1-4H3;1H/t33-;/m0./s1
Chemical Name	5-[5-chloro-2-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(5-cyano-1,2-dimethylpyrrol-3-yl)-N-(4-hydroxyphenyl)-1,2-dimethylpyrrole-3-carboxamide;hydrochloride
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, 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	S65487 hydrochloride attaches itself to BCL-2's BH3 hydrophobic groove. S65487 hydrochloride has IC50s in the low nM range and inhibits cell proliferation in a panel of hematological cancer cell lines via inducing apoptosis[1].
ln Vivo	S65487 hydrochloride causes total remission of BCL-2-dependent RS4;11 tumors in vivo following a single intravenous (IV) injection. Once weekly IV treatment of S65487 hydrochloride in conjunction with the MCL-1-specific inhibitor S64315/MIK665 results in well tolerated doses of strong and permanent tumor shrinkage in xenograft models of lymphoid malignancies in mice and rats[1].
References	[1]. Abstract 1276: Identification of S65487/VOB560 as a potent and selective intravenous 2nd-generation BCL-2 inhibitor active in wild-type and clinical mutants resistant to Venetoclax. Cancer Research. July 2021.

Solubility Data

Solubility (In Vitro)

DMSO : 90 mg/mL (119.41 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 4.5 mg/mL (5.97 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 45.0 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: ≥ 4.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 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 45.0 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: ≥ 4.5 mg/mL (5.97 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 45.0 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	1.3942 mL	6.9710 mL	13.9419 mL
	5 mM	0.2788 mL	1.3942 mL	2.7884 mL
	10 mM	0.1394 mL	0.6971 mL	1.3942 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.