Tandutinib (MLN518)

Validation & Quality Control

Product Citations(1)

Br J Cancer, 2012, 107(10),1702-13

Quality Control & MSDS

Related Compound Libraries

Tandutinib (MLN518) is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

Product Information

Combination Therapy

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Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1119	XL-184 free base (Cabozantinib)	<1 mg/mL	100 mg/mL	<1 mg/mL
S2194	R406	<1 mg/mL	126 mg/mL	8 mg/mL
S1526	Quizartinib (AC220)	<0.3 mg/mL	33.2 mg/mL	<0.5 mg/mL
S1018	Dovitinib (TKI-258)	<1 mg/mL	30 mg/mL	<1 mg/mL
S2692	TG101209	<1 mg/mL	102 mg/mL	<1 mg/mL
S2158	KW 2449	<1 mg/mL	67 mg/mL	67 mg/mL
S1244	Amuvatinib (MP-470)	<1 mg/mL	32 mg/mL	<1 mg/mL
S2769	Dovitinib Dilactic acid (TKI258 Dilactic acid)	70 mg/mL	90 mg/mL	<1 mg/mL
S1043	Tandutinib (MLN518)	<1 mg/mL	5 mg/mL	19 mg/mL
S1181	ENMD-2076	1 mg/mL	105 mg/mL	<1 mg/mL
S8023	TCS 359	<1 mg/mL	15 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Product Citations Tech Support & FAQs

Biological Activity

Description	Tandutinib (MLN518, CT53518) is an ATP-competitive and highly selective inhibitor of Flt3, PDGFRβ and c-Kit with IC50 of 0.22 μM, 0.20 μM and 0.17 μM, respectively.
Targets	FLT3	PDGFRβ	c-Kit
IC50	0.22 μM	0.20 μM	0.17 μM ^[1]
In vitro	Tandutinib has little activity against EGFR, FGFR, KDR, InsR, Src, Abl, PKC, PKA and MAPKs. Tandutinib inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM. Tandutinib also inhibits the proliferation of human leukemia Ba/F3 cells containing FLT3-ITD mutations with IC50 values of 10-30 nM, and the FLT3-ITD-positive Molm-13 and Molm-14 cells with an IC50 of 10 nM. In FLT3-ITD-positive Molm-14 cells but not the FLT3-ITD-negative THP-1 cells, Tandutinib treatment leads to significant apoptosis by 51% and 78% at 24 and 96 hours, respectively, due to specific FLT3 inhibition. ^[1] Tandutinib preferentially inhibits the growth of blast colonies from FLT3 ITD-positive compared with ITD-negative patients with AML, without affecting colony formation by normal human progenitor cells. ^[2]
In vivo	Oral administration of Tandutinib at 60 mg/kg bid significantly increases the survival in mice bearing Ba/F3 cells expressing W51 FLT3-ITD mutant, and gives a significant reduction in mortality in a mouse bone marrow transplantation model. ^[1] Tandutinib treatment at 180 mg/kg twice daily has mild toxicity toward normal hematopoiesis, however, it is a dose at which Tandutinib is effective in treating FLT3 ITD-positive leukemia in mice. ^[2]
Clinical Trials	A Phase II study of Tandutinib in androgen-independent prostate cancer with bone metastases has been completed.
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell based receptor autophosphorylation assays	Autophosphorylation of PDGFR family kinase assays are cell-based enzyme-linked immunosorbent (ELISA) assays using CHO cells expressing wild-type PDGFRβ, chimeric protein PDGFRβ/c-Kit, and PDGFRβ/Flt3 which contain the extracellular and transmembrane domains of PDGFRβ and the cytoplasmic domain of c-Kit, and Flt-3. Cells are grown to confluency in 96-well microtiter plates under standard tissue culture conditions, followed by serum starvation for 16 hours. Briefly, quiescent cells are incubated at 37 °C with increasing concentrations of Tandutinib for 30 minutes followed by the addition of 8 nM PDGF-BB for 10 minutes. Cells are lysed in 100 mM Tris, pH 7.5, 750 mM NaCl, 0.5% Triton X-100, 10 mM sodium pyrophosphate, 50 mM NaF, 10 μg/mL aprotinin, 10 μg/mL leupeptin, 1 mM phenylmethylsulfonyl fluoride, 1 mM sodium vanadate, and the lysate is cleared by centrifugation at 15,000g for 5 minutes. Clarified lysates are transferred into a second microtiter plate in which the wells are previously coated with 500 ng/well of 1B5B11 anti-PDGFRβ mAb and then incubated for 2 hours at room temperature. After washing three times with binding buffer (0.3% gelatin, 25 mM HEPES, pH 7.5, 100 mM NaCl, 0.01% Tween 20), 250 ng/mL of rabbit polyclonal anti-phosphotyrosine antibody is added and plates are incubated at 37 °C for 60 minutes. Subsequently, each well is washed three times with binding buffer and incubated with 1 μg/mL of horseradish peroxidase-conjugated anti-rabbit antibody at 37 °C for 60 minutes. Wells are washed prior to adding 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and the rate of substrate formation is monitored at 650 nm.

Cell based receptor autophosphorylation assays

Autophosphorylation of PDGFR family kinase assays are cell-based enzyme-linked immunosorbent (ELISA) assays using CHO cells expressing wild-type PDGFRβ, chimeric protein PDGFRβ/c-Kit, and PDGFRβ/Flt3 which contain the extracellular and transmembrane domains of PDGFRβ and the cytoplasmic domain of c-Kit, and Flt-3. Cells are grown to confluency in 96-well microtiter plates under standard tissue culture conditions, followed by serum starvation for 16 hours. Briefly, quiescent cells are incubated at 37 °C with increasing concentrations of Tandutinib for 30 minutes followed by the addition of 8 nM PDGF-BB for 10 minutes. Cells are lysed in 100 mM Tris, pH 7.5, 750 mM NaCl, 0.5% Triton X-100, 10 mM sodium pyrophosphate, 50 mM NaF, 10 μg/mL aprotinin, 10 μg/mL leupeptin, 1 mM phenylmethylsulfonyl fluoride, 1 mM sodium vanadate, and the lysate is cleared by centrifugation at 15,000g for 5 minutes. Clarified lysates are transferred into a second microtiter plate in which the wells are previously coated with 500 ng/well of 1B5B11 anti-PDGFRβ mAb and then incubated for 2 hours at room temperature. After washing three times with binding buffer (0.3% gelatin, 25 mM HEPES, pH 7.5, 100 mM NaCl, 0.01% Tween 20), 250 ng/mL of rabbit polyclonal anti-phosphotyrosine antibody is added and plates are incubated at 37 °C for 60 minutes. Subsequently, each well is washed three times with binding buffer and incubated with 1 μg/mL of horseradish peroxidase-conjugated anti-rabbit antibody at 37 °C for 60 minutes. Wells are washed prior to adding 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and the rate of substrate formation is monitored at 650 nm.

Cell Assay: ^[1]

Cell lines	Ba/F3, Molm-13, Molm-14, HL60, AML193, KG-1, KG-1a, THP-1, and RS4;11
Concentrations	Dissolved in DMSO, final concentrations ~30 μM
Incubation Time	~7 days
Method	Cells are exposed to increasing concentrations of Tandutinib (0.004-30 μM). Cells are grown for 3-7 days in tissue culture, and viable cells, determined by Trypan blue dye exclusion, are counted. At daily intervals, cells are harvested, washed, and resuspended in 100 uL binding buffer containing 10 mM HEPES (pH 7.4), 140 mM NaCl, and 2.5 mM CaCl₂. Annexin V-FITC (100 ng) and propidium iodide (250 ng) are added to the cell suspension followed by incubation at room temperature for 15 minutes. Flow cytometry is performed immediately after staining on a FACSort flow cytometer with excitation at 488 nm. Fluorescence of annexin V-FITC and DNA propidium iodide staining are measured at 515 nm and 585 nm, respectively.

Animal Study: ^[1]

Animal Models	Female athymic nude (nu/nu) mice injected with Ba/F3 cells expressing W51 FLT3-ITD mutant
Formulation	Suspended in a 0.5% methylcellulose (MC) in water solution
Dosages	40-120 mg/kg/day
Administration	Orally by gavage

1

References

Chemical Information

Download Tandutinib (MLN518) SDF

Molecular Weight (MW)	562.7
Formula	C₃₁H₄₂N₆O₄
CAS No.	387867-13-2, 1227636-16-9 (3H2O)
Synonyms	CT53518

Solubility (25°C) DMSO 5 mg/mL Water <1 mg/mL Ethanol 19 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	N-(4-isopropoxyphenyl)-4-(6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-yl)piperazine-1-carboxamide

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Research Area

Product Citations (1)

Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro. [Pfister C, et al. Br J Cancer 2012;107(10),1702-13]
PubMed: 23047550

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Dovitinib (TKI258, CHIR258) is a novel multi-target inhibitor for Flt3, c-Kit, FGFR1/3, VEGFR1/2/3, PDGFRα/β with IC50 of 1 nM, 2 nM, 8 nM/9 nM and 10 nM/13 nM/8 nM, 210 nM/27 nM respectively.
ENMD-2076

ENMD-2076 is a selective inhibitor of Aurora A and Aurora B with IC50 of 14 nM and 350 nM and also inhibits Flt3, Flt4 and VEGFR2 with IC50 of 1.86 nM/15.9 nM and 58.2 nM, respectively.
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MP-470 (Amuvatinib) is a potent and multi-targeted inhibitor of c-Kit^D816H, PDGFα^V561D and Flt3^D835Y with IC50 of 10 nM, 40 nM and 81 nM, respectively.
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ENMD-2076 L-(+)-Tartaric acid is the tartaric acid of ENMD-2076, a selective inhibitor of Aurora A and Aurora B with IC50 of 14 nM and 350 nM and also inhibits Flt3, Flt4 and VEGFR2 with IC50 of 1.86 nM, 15.9 nM and 58.2 nM, respectively.
KW 2449

KW-2449 potently inhibits Flt3, Abl and Aurora A with IC50 of 6.6 nM, 14 nM and 48 nM, respectively.
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R406 is a potent Syk inhibitor with IC50 of 41 nM and also potently inhibits Flt3.
TG101209

TG101209 is a potent inhibitor of JAK2, Flt3 and RET with IC50 of 6 nM, 25 nM and 17 nM, respectively.
Dovitinib Dilactic acid (TKI258 Dilactic acid)

Dovitinib (TKI258, CHIR-258) is a multitargeted tyrosine kinase inhibitor of FLT3 and c-KIT with IC50 of 1 nM and 2 nM, respectively.
TCS 359

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RTKs and Angiogenesis Related Products

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Tandutinib (MLN518) + Cytarabine(Cytosar-U)	Tandutinib markedly reduces the amount of Cytarabine or Daunorubicin necessary to achieve any given amount of anti-proliferative effect, suggesting that the combination of Tandutinib and Cytarabine/Daunorubicin is strongly synergistic. ^[3]
Tandutinib (MLN518) + daunorubicin-hcl-daunomycin-hcl	Tandutinib markedly reduces the amount of Cytarabine or Daunorubicin necessary to achieve any given amount of anti-proliferative effect, suggesting that the combination of Tandutinib and Cytarabine/Daunorubicin is strongly synergistic. ^[3]

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Validation & Quality Control

Product Citations(1)

Quality Control & MSDS

Related Compound Libraries

Tandutinib (MLN518) is available in the following compound libraries:

Product Information

Combination Therapy

Compare FLT3 Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[1]

References

Chemical Information

Research Area

Product Citations (1)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related FLT3 Inhibitors

RTKs and Angiogenesis Related Products

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Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1119	XL-184 free base (Cabozantinib)	<1 mg/mL	100 mg/mL	<1 mg/mL
S2194	R406	<1 mg/mL	126 mg/mL	8 mg/mL
S1526	Quizartinib (AC220)	<0.3 mg/mL	33.2 mg/mL	<0.5 mg/mL
S1018	Dovitinib (TKI-258)	<1 mg/mL	30 mg/mL	<1 mg/mL
S2692	TG101209	<1 mg/mL	102 mg/mL	<1 mg/mL
S2158	KW 2449	<1 mg/mL	67 mg/mL	67 mg/mL
S1244	Amuvatinib (MP-470)	<1 mg/mL	32 mg/mL	<1 mg/mL
S2769	Dovitinib Dilactic acid (TKI258 Dilactic acid)	70 mg/mL	90 mg/mL	<1 mg/mL
S1043	Tandutinib (MLN518)	<1 mg/mL	5 mg/mL	19 mg/mL
S1181	ENMD-2076	1 mg/mL	105 mg/mL	<1 mg/mL
S8023	TCS 359	<1 mg/mL	15 mg/mL	<1 mg/mL

Choose Your Country or Region

Product Categories

Tandutinib (MLN518)

Validation & Quality Control

Product Citations(1)

Quality Control & MSDS

Related Compound Libraries

Tandutinib (MLN518) is available in the following compound libraries:

Product Information

Combination Therapy

Compare FLT3 Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [1]

Animal Study: [1]

References

Chemical Information

Research Area

Product Citations (1)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related FLT3 Inhibitors

RTKs and Angiogenesis Related Products

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Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[1]