KSQ-4279 (USP1-IN-1) is a potent, first-in-class, selective USP1 inhibitor. KSQ-4279 has anti-cancer activities.

Physicochemical Properties

Molecular Formula	C27H25F3N8O
Molecular Weight	534.54
Exact Mass	534.21
CAS #	2446480-97-1
Related CAS #	2446480-97-1;
PubChem CID	150782011
Appearance	White to light yellow solid powder
LogP	4
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	39
Complexity	823
Defined Atom Stereocenter Count	0
SMILES	C1(C2=C(OC)N=CN=C2C2CC2)=NC=C2C=NN(CC3=CC=C(C4N(C(C)C)C=C(C(F)(F)F)N=4)C=C3)C2=N1
InChi Key	KCBWAFJCKVKYHO-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H25F3N8O/c1-15(2)37-13-20(27(28,29)30)35-24(37)18-6-4-16(5-7-18)12-38-25-19(11-34-38)10-31-23(36-25)21-22(17-8-9-17)32-14-33-26(21)39-3/h4-7,10-11,13-15,17H,8-9,12H2,1-3H3
Chemical Name	6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine
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

ln Vitro	KSQ-4279 causes S-cycle cell cycle, considerable accumulation of γ-H2A histone family member X (ϒH2AX), and enhances cell carcinogenesis in BRCA1/2 mutant breast cancer cells [1].
ln Vivo	KSQ-4279 displayed dose-dependent, strong and sustained anti-tumor regression in numerous TNBC and advanced cancer PDX models with diverse genomic state, including BRCA1 mutant and wild-type models [1].
References	[1]. Targeting the DNA damage response beyond poly(ADP-ribose) polymerase inhibitors: novel agents and rational combinations. Curr Opin Oncol. 2022 Sep 1;34(5):559-569.
Additional Infomation	USP1 inhibitor KSQ-4279 is an orally bioavailable selective inhibitor of the ubiquitin specific protease 1 (USP1), with apoptosis-inducing, tumor-sensitizing and antineoplastic activities. Upon oral administration, USP1 inhibitor KSQ-4279 specifically binds to and inhibits the activity of USP1, thereby blocking USP1-mediated deubiquitylating activity. This blocks the ubiquitin proteasome degradation pathway, prevents the degradation of defective proteins, and leads to an accumulation of mono-ubiquinated substrates. This induces the unfolded protein response (UPR). This may induce cell cycle arrest, reduce the expression of certain anti-apoptotic proteins, induce tumor cell apoptosis, inhibit tumor cell growth, and may sensitize tumor cells to DNA-targeting chemotherapeutics. USP1, a deubiquitinating enzyme overexpressed in various tumor cell types, plays a key role in the correct folding and deubiquitination of proteins and facilitates DNA repair via its role regulating the Fanconi anemia complex and translesion synthesis.

Solubility Data

Solubility (In Vitro)

DMSO : ~80 mg/mL (~149.66 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2 mg/mL (3.74 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 20.0 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 mg/mL (3.74 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 20.0 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	1.8708 mL	9.3538 mL	18.7077 mL
	5 mM	0.3742 mL	1.8708 mL	3.7415 mL
	10 mM	0.1871 mL	0.9354 mL	1.8708 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.