MLT-231 is a specific allosteric MALT1 inhibitor (antagonist) with IC50 of 9 nM. MLT-231 specifically blocks endogenous BCL10 cleavage with IC50 of 160 nM. MLT-23 has anticancer effect in ABC-DLBCL xenograft models.

Physicochemical Properties

Molecular Formula	C19H19CLF3N7O2
Molecular Weight	469.848072290421
Exact Mass	469.124
CAS #	2682102-10-7
PubChem CID	146680905
Appearance	White to off-white solid powder
LogP	2.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	3
Heavy Atom Count	32
Complexity	665
Defined Atom Stereocenter Count	2
SMILES	C[C@H]1COC[C@@H](N1C2=C(C=NC3=CC(=NN32)Cl)NC(=O)NC4=CC(=NC=C4)C(F)(F)F)C
InChi Key	BFPCFGGFGQMJQG-QWRGUYRKSA-N
InChi Code	InChI=1S/C19H19ClF3N7O2/c1-10-8-32-9-11(2)29(10)17-13(7-25-16-6-15(20)28-30(16)17)27-18(31)26-12-3-4-24-14(5-12)19(21,22)23/h3-7,10-11H,8-9H2,1-2H3,(H2,24,26,27,31)/t10-,11-/m0/s1
Chemical Name	1-[2-chloro-7-[(3S,5S)-3,5-dimethylmorpholin-4-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[2-(trifluoromethyl)pyridin-4-yl]urea
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	MLT-231 (19.5–10,000 nM) prevents OCI-Ly3 cells from proliferating. MLT-231 (50-5000 nM; 24 hours) suppresses the expression of the NF-κB target gene IRF4 while causing the uncleaved forms of its substrates, CYLD, BCL10, and RELB, to accumulate[1].
ln Vivo	In the ABC-DLBCL xenograft model, MLT-231 (10-100 mg/kg; po; bid schedule for 2 weeks) exhibits in vivo efficacy[1]. Following IV administration of MLT-231 (1 mg/kg) to BALB/c mice, the CL, t1/2, and Vss are, respectively, 11 mL/min/kg, 1.9 hours, and 1.5 L/kg[1]. Following intravenous administration of MLT-231 (1 mg/kg) to Sprague-Dawley rats, the CL, t1/2, and Vss are 41 mL/min/kg, 3.2 hours, and 9.4 L/kg, respectively[1]. The AUC0-24, Cmax, and F values for MLT-231 (3 mg/kg; po; BALB/c mice) are 3096 nM/h, 549 nM, and 99%, respectively[1]. The AUC0-24, Cmax, and F values for MLT-231 (3 mg/kg; po; Sprague-Dawley rats) are 547 nM/h, 46 nM, and 61%, correspondingly.
Cell Assay	Western Blot Analysis[1] Cell Types: OCI-Ly3 cells Tested Concentrations: 50-5000 nM Incubation Duration: 24 hrs (hours) Experimental Results: NF-κB target gene IRF4 was suppressed.
Animal Protocol	Animal/Disease Models: Scid-beige mice (OCI-Ly10 ABC-DLBCL type xenograft model)[1] Doses: 10, 30, and 100 mg/kg Route of Administration: Po; bid schedule for 2 weeks Experimental Results: Led to tumor stasis, while being well tolerated.
References	[1]. Discovery of Potent, Highly Selective, and In Vivo Efficacious, Allosteric MALT1 Inhibitors by Iterative Scaffold Morphing [published online ahead of print, 2020 Nov 30]. J Med Chem. 2020;10.1021/acs.jmedchem.0c01245.

Solubility Data

Solubility (In Vitro)

DMSO: 110 mg/mL (234.12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6 mg/mL (12.77 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 60.0 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: ≥ 5.5 mg/mL (11.71 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 55.0 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	2.1283 mL	10.6417 mL	21.2834 mL
	5 mM	0.4257 mL	2.1283 mL	4.2567 mL
	10 mM	0.2128 mL	1.0642 mL	2.1283 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.