LY3177833, a novel and potent CDC7 (Cell Division Cycle 7-related Protein Kinase) and pMCM2 inhibitor with IC50 values of 3.3 nM and 290 nM, respectively, was extracted from patent US 20140275131 and patent WO 2014143601 A1 compound 4.

Physicochemical Properties

Molecular Formula	C16H12FN5O
Molecular Weight	309.297785758972
Exact Mass	309.103
Elemental Analysis	C, 62.13; H, 3.91; F, 6.14; N, 22.64; O, 5.17
CAS #	1627696-51-8
Related CAS #	LY3177833 monhydrate;1627696-53-0
PubChem CID	81689696
Appearance	White to off-white solid powder
LogP	1
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	477
Defined Atom Stereocenter Count	1
SMILES	O=C1N[C@@](C)(C2=NC=NC=C2F)C3=C1C=C(C4=CNN=C4)C=C3
InChi Key	KNLVLWZENYQYRT-MRXNPFEDSA-N
InChi Code	InChI=1S/C16H12FN5O/c1-16(14-13(17)7-18-8-19-14)12-3-2-9(10-5-20-21-6-10)4-11(12)15(23)22-16/h2-8H,1H3,(H,20,21)(H,22,23)/t16-/m1/s1
Chemical Name	(3R)-3-(5-fluoropyrimidin-4-yl)-3-methyl-6-(1H-pyrazol-4-yl)-2H-isoindol-1-one
Synonyms	LY-3177833; LY3177833; LY 3177833
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	Cdc7 (IC50 = 3.3 nM); pMCM2 (IC50 = 290 nM)
ln Vitro	LY3177833 (10 μM; 4 days) raises the SA-β-gal content in Hep3B cells[2].
ln Vivo	LY3177833 (Example 4; 10.4-31.2 mg/kg; oral gavage; twice a day; for 2 weeks; female athymic Balb/c nude mice with SW620 cells) significantly reduces tumors in a dose-dependent manner. Additionally, two weeks after stopping the medication, no discernible tumor growth is seen[1].
Cell Assay	Cell Line: Hep3B cells Concentration: 10 μM Incubation Time: 4 days Result: Increased the expression of human SA-β-gal.
Animal Protocol	Female athymic Balb/c nude mice (5-6 weeks old) with SW620 cells[1] 10.4 mg/kg, 20.8 mg/kg and 31.2 mg/kg Oral gavage; twice a day for 2 weeks
References	[1]. CDC7 Inhibitors. Patent WO2014143601A1. [2]. First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated β-galactosidase. Chem Sci. 2020 Jun 17;11(28):7292-7301.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 30 mg/mL (~97 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.08 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 (8.08 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 25.0 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: ≥ 2.5 mg/mL (8.08 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	3.2331 mL	16.1655 mL	32.3311 mL
	5 mM	0.6466 mL	3.2331 mL	6.4662 mL
	10 mM	0.3233 mL	1.6166 mL	3.2331 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.