CAS 387867-13-2|Tandutinib (MLN518)

Introduction：Basic information about CAS 387867-13-2|Tandutinib (MLN518), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Tandutinib (MLN518) BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Synonyms

Common Name	Tandutinib (MLN518)
CAS Number	387867-13-2	Molecular Weight	562.703
Density	1.2±0.1 g/cm3	Boiling Point	769.5±60.0 °C at 760 mmHg
Molecular Formula	C₃₁H₄₂N₆O₄	Melting Point	177-178°C
MSDS	/	Flash Point	419.2±32.9 °C

Names

Name	Tandutinib(CT 53518)
Synonym	More Synonyms

Tandutinib (MLN518) BiologicalActivity

Description	Tandutinib (MLN518, CT53518) is a potent FLT3 antagonist with IC50 of 0.22 μM, also inhibits PDGFR and c-Kit, 15 to 20-fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR and KDR. IC50 value: 0.22 uM [1]Target: Flt3; PDGFRβ; c-Kitin 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].
Related Catalog	Signaling Pathways >>Protein Tyrosine Kinase/RTK >>FLT3Research Areas >>Cancer
References	[1]. Kelly LM, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell, 2002, 1(5), 421-432. [2]. Griswold IJ, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood, 2004, 104(9), 2912-2918. [3]. Schittenhelm MM, et al. The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin. Cell Cycle, 2009, 8(16), 2621-2630. [4]. Salama Y, et al. The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling. Biochem Biophys Res Commun. 2017 Aug 19;490(2):209-216.

Description

Tandutinib (MLN518, CT53518) is a potent FLT3 antagonist with IC50 of 0.22 μM, also inhibits PDGFR and c-Kit, 15 to 20-fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR and KDR. IC50 value: 0.22 uM [1]Target: Flt3; PDGFRβ; c-Kitin 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].

Related Catalog

Signaling Pathways >>Protein Tyrosine Kinase/RTK >>FLT3Research Areas >>Cancer

References

[1]. Kelly LM, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell, 2002, 1(5), 421-432.

[2]. Griswold IJ, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood, 2004, 104(9), 2912-2918.

[3]. Schittenhelm MM, et al. The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin. Cell Cycle, 2009, 8(16), 2621-2630.

[4]. Salama Y, et al. The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling. Biochem Biophys Res Commun. 2017 Aug 19;490(2):209-216.

Chemical & Physical Properties

Density	1.2±0.1 g/cm3
Boiling Point	769.5±60.0 °C at 760 mmHg
Melting Point	177-178°C
Molecular Formula	C₃₁H₄₂N₆O₄
Molecular Weight	562.703
Flash Point	419.2±32.9 °C
Exact Mass	562.326782
PSA	92.29000
LogP	3.48
Vapour Pressure	0.0±2.6 mmHg at 25°C
Index of Refraction	1.611
InChIKey	UXXQOJXBIDBUAC-UHFFFAOYSA-N
SMILES	COc1cc2c(N3CCN(C(=O)Nc4ccc(OC(C)C)cc4)CC3)ncnc2cc1OCCCN1CCCCC1
Storage condition	Refrigerator

Safety Information

Hazard Codes	T,N,Xi,F
Risk Phrases	R25:Toxic if swallowed. R34:Causes burns. R50:Very Toxic to aquatic organisms. R40:Limited evidence of a carcinogenic effect. R36/37/38:Irritating to eyes, respiratory system and skin .
Safety Phrases	S23-S37-S45-S61-S36-S26-S16
RIDADR	UN 1751 6.1/PG 2
WGK Germany	2
RTECS	AF8575000
Packaging Group	II
Hazard Class	6.1
HS Code	29154000

Customs

HS Code	29154000

Synonyms

4-(6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl)piperazine-1-carboxylic acid (4-isopropoxyphenyl)amide

MLN 518

Tandutinib

4-{6-methoxy-7-[3-(piperidin-1-yl)propoxy]quinazolin-4-yl}-N-[4-(propan-2-yloxy)phenyl]piperazine-1-carboxamide

N-(4-Isopropoxyphenyl)-4-{6-methoxy-7-[3-(piperidin-1-yl)propoxy]quinazolin-4-yl}piperazine-1-carboxamide

Tandutinib for research

1-Piperazinecarboxamide, 4-[6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinyl]-N-[4-(1-methylethoxy)phenyl]-

N-(4-Isopropoxyphenyl)-4-{6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinyl}-1-piperazinecarboxamide

UNII:E1IO3ICJ9A

Unii-E1io3icj9a

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