Tivumecirnon (FLX475) is a potent CCR4 antagonist tumor agent that blocks the regulation of anti-immune responses that effectively interferes with T cells and has anti-tumor activity.

Physicochemical Properties

Molecular Formula	C24H27CL2F3N6O
Molecular Weight	543.41
Exact Mass	542.157
CAS #	2174938-78-2
PubChem CID	134210715
Appearance	Off-white to light yellow solid powder
LogP	4.6
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	6
Heavy Atom Count	36
Complexity	747
Defined Atom Stereocenter Count	2
SMILES	N1(CCO)CCC[C@H](C2CN(C3N=C4N([C@@H](C5=CC=C(Cl)C=C5Cl)C)N=C(C(F)(F)F)C4=NC=3)C2)C1
InChi Key	AKSVALRPYDVQBS-CABCVRRESA-N
InChi Code	InChI=1S/C24H27Cl2F3N6O/c1-14(18-5-4-17(25)9-19(18)26)35-23-21(22(32-35)24(27,28)29)30-10-20(31-23)34-12-16(13-34)15-3-2-6-33(11-15)7-8-36/h4-5,9-10,14-16,36H,2-3,6-8,11-13H2,1H3/t14-,15+/m1/s1
Chemical Name	2-[(3R)-3-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-(trifluoromethyl)pyrazolo[3,4-b]pyrazin-6-yl]azetidin-3-yl]piperidin-1-yl]ethanol
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

References

[1]. Chemokine receptor modulators and uses thereof. WO2018022992. [2]. Abstract 2485: A combined mregDC and Treg signature associates with antitumor efficacy of CCR4 antagonist tivumecirnon FLX475. Cancer Res 15 March 2024; 84 (6_Supplement): 2485. [3]. 629-C Phase 2 safety and efficacy of oral CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab in subjects with non-small cell lung cancer not previously treated with checkpoint inhibitor. 2023. [4]. Clinical and biological activity of FLX475, an oral CCR4 antagonist, in advanced cancer. Journal of Clinical Oncology. 2023. 41, 2625-2625.

Additional Infomation

FLX475 is a small molecule CCR4 antagonist being investigated for the treatment of cancer. Tivumecirnon is an orally available, small molecule antagonist of C-C chemokine receptor type 4 (CCR4) with potential immunomodulatory and antineoplastic activities. Upon oral administration, tivumecirnon inhibits the binding of CCR4 to its signaling molecules, thereby blocking the recruitment of regulatory T-cells (Tregs) to the tumor microenvironment (TME). This may abrogate the immunosuppressive effects of Tregs and promote an effective anti-tumor immune response. CCR4, a chemokine receptor normally expressed on circulating and tissue-resident T-cells, is highly expressed on circulating Tregs and is associated with poor prognosis in certain cancers.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~184.02 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.60 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	1.8402 mL	9.2012 mL	18.4023 mL
	5 mM	0.3680 mL	1.8402 mL	3.6805 mL
	10 mM	0.1840 mL	0.9201 mL	1.8402 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.