Tandutinib HCl (MLN518 HCl) is a potent and specific inhibitor of FLT3 with IC50 of 0.22 μM, and also inhibits c-Kit and PDGFR with IC50 of 0.17 μM and 0.20 μM, respectively. Tandutinib HCl is indicated for acute myeloid leukemia and has the ability to cross the BBB (blood-brain barrier).

Physicochemical Properties

Molecular Formula	C31H43CLN6O4
Molecular Weight	599.163926362991
Exact Mass	598.303
CAS #	2438900-70-8
Related CAS #	Tandutinib;387867-13-2
PubChem CID	138911453
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	10
Heavy Atom Count	42
Complexity	783
Defined Atom Stereocenter Count	0
SMILES	Cl.O(C1C(=CC2=C(C=1)N=CN=C2N1CCN(C(NC2C=CC(=CC=2)OC(C)C)=O)CC1)OC)CCCN1CCCCC1
InChi Key	FOEBHLNUCNUHHJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C31H42N6O4.ClH/c1-23(2)41-25-10-8-24(9-11-25)34-31(38)37-17-15-36(16-18-37)30-26-20-28(39-3)29(21-27(26)32-22-33-30)40-19-7-14-35-12-5-4-6-13-35;/h8-11,20-23H,4-7,12-19H2,1-3H3,(H,34,38);1H
Chemical Name	4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide;hydrochloride
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	FLT3 0.22 μM (IC50) c-Kit 0.17 μM (IC50) PDGFR 0.2 μM (IC50)
ln Vitro	In Ba/F3 cells expressing various FLT3-ITD mutations, tantutinib (0-3 μM; 30 minutes) treatment suppresses FLT3-autophosphorylation and IL-3-independent cell proliferation with an IC50 of 10-100 nM[1]. FLT3-ITD-positive AML cells undergo apoptosis when treated with tantutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells)[1]. Tandutinib suppresses FLT3-ITD phosphorylation (IC50 of ~30 nM) in human FLT3-ITD-positive AML cell lines. Pretreating the Molm-14 cells with 100–300 nM tantutinib effectively blocks constitutively high levels of Akt phosphorylation, much as it does Erk2[1]. Tandutinib has an IC50 of 10 nM, which inhibits the FLT3-ITD-positive Molm-13 and Molm-14 cells from proliferating. as well as signaling via the PI3 kinase and MAP kinase pathways[1].
ln Vivo	Tandutinib treatment results in a statistically significant improvement in survival, which is extended on average by 20 days in athymic nude mice (60 mg/kg; oral gavage; daily; for 35 days)[1].
Cell Assay	Apoptosis Analysis[1] Cell Types: Molm-14 and THP-1 AML cells Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours), 96 hrs (hours) Experimental Results: Induced apoptosis in FLT3 -ITD-positive AML cells. Western Blot Analysis[1] Cell Types: Ba/F3 cells Tested Concentrations: 0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM Incubation Duration: 30 minutes Experimental Results: In Ba/F3 cells express different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation.
Animal Protocol	Animal/Disease Models: Athymic nude mice injected with Ba/F3 cells[1] Doses: 60 mg/kg Route of Administration: po (oral gavage); daily; for 35 days Experimental Results: Caused a statistically significant increase in survival that was extended on average by 20 days.
References	[1]. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell. 2002 Jun;1(5):421-32. [2]. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood. 2004 Nov 1;104(9):2912-8. [3]. P-glycoprotein and breast cancer resistance protein affect disposition of tandutinib, a tyrosine kinase inhibitor. Drug Metab Lett. 2010 Dec;4(4):201-12.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (166.90 mM) H2O : 100 mg/mL (166.90 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.17 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 (4.17 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: 100 mg/mL (166.90 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6690 mL	8.3450 mL	16.6900 mL
	5 mM	0.3338 mL	1.6690 mL	3.3380 mL
	10 mM	0.1669 mL	0.8345 mL	1.6690 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.