TL-895 is a potent, orally bioactive, ATP-competitive, selective and irreversible BTK inhibitor (antagonist) with IC50 and Kis of 1.5 nM and 11.9 nM respectively. TL-895 may be used in JAKi relapsed/refractory myelofibrosis, acute myeloid leukemia, COVID-19 and cancer research.

Physicochemical Properties

Molecular Formula	C25H26FN5O2
Molecular Weight	447.504648685455
Exact Mass	447.207
CAS #	1415823-49-2
PubChem CID	86721856
Appearance	White to off-white solid powder
LogP	4.1
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	643
Defined Atom Stereocenter Count	0
SMILES	FC1(CNC2C(=C(N)N=CN=2)C2C=CC(=CC=2)OC2C=CC=CC=2)CCN(C(C=C)=O)CC1
InChi Key	OXOXFDSEGFLWLU-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H26FN5O2/c1-2-21(32)31-14-12-25(26,13-15-31)16-28-24-22(23(27)29-17-30-24)18-8-10-20(11-9-18)33-19-6-4-3-5-7-19/h2-11,17H,1,12-16H2,(H3,27,28,29,30)
Chemical Name	1-[4-[[[6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl]amino]methyl]-4-fluoropiperidin-1-yl]prop-2-en-1-one
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

IC50: 1.5 nM; Ki: 11.9 nM (BTK)[1]

References

[1]. Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases. J Med Chem. 2019 Sep 12;62(17):7643-7655. [2]. Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review. Int J Mol Sci. [3]. A Study of TL-895 With Standard Available Treatment Versus Standard Available Treatment for the Treatment of COVID-19 in Patients With Cancer. [4]. Study of TL-895 in Subjects With Myelofibrosis.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (558.66 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.65 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 20.8 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: ≥ 2.08 mg/mL (4.65 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 20.8 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: ≥ 2.08 mg/mL (4.65 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 20.8 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	2.2346 mL	11.1732 mL	22.3464 mL
	5 mM	0.4469 mL	2.2346 mL	4.4693 mL
	10 mM	0.2235 mL	1.1173 mL	2.2346 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.