GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

4-(2,4-dichloro-5-methoxyphenylamino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Bosutinib (SKI-606) is a novel, dualSrc/Ablinhibitor withIC50of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity ofPI3K/AKT/mTOR,MAPK/ERKandJAK/STAT3signaling pathways by blocking the phosphorylation lev
In vitro

Bosutinib is selective for Src over non-Src family kinases with an IC50 of 1.2 nM, and potently inhibits Src-dependent cell proliferation with an IC50 of 100 nM. Bosutinib significantly inhibits the proliferation of Bcr-Abl-positive leukemia cell lines KU812, K562, and MEG-01 but not Molt-4, HL-60, Ramos, and other leukemia cell lines, with IC50 of 5 nM, 20 nM and 20 nM, respectively, more potently than that of STI-571. Similar to STI-571, Bosutinib displays antiproliferative activity against the Abl-MLV-transformed fibroblasts with IC50 of 90 nM. Bosutinib ablates tyrosine phosphorylation of Bcr-Abl and STAT5 in CML cells and of v-Abl expressed in fibroblasts at the concentration of ~50 nM, 10-25 nM and 200 nM, respectively, leading to the Bcr-Abl downstream signaling inhibition of Lyn/Hck phosphorylation. Although unable to inhibit the proliferation and survival of breast cancer cells, Bosutinib significantly decreases the motility and invasion of breast cancer cells with IC50 of ~250 nM, involved with an increase in cell-to-cell adhesion and membrane localization of β-catenin.

In vivo

Bosutinib (60 mg/kg/day) is active against Src-transformed fibroblasts xenografts and HT29 xenografts in nude mice with T/C of 18% and 30%, respectively. Oral administration of Bosutinib for 5 days significantly suppresses K562 tumor growth in mice in a dose-dependent manner, with the large tumors eradicated at dose of 100 mg/kg and tumor free at 150 mg/kg without overt toxicity. As being inactive against Colo205 xenografts in nude mice at 50 mg/kg twice daily, Bosutinib dosing at 75 mg/kg twice daily is necessary against Colo205 xenografts, and increasing the dose of Bosutinib has no additional benefit, in contrast to the significant dose-dependent ability against HT29 xenografts.
Cell Data

cell lines：Gli-Luc/MEF cells

Concentrations：Dissolved in DMSO, final concentrations ~1 μM

Incubation Time：72 hours

Powder Purity:≥98%

Specifications

Synonyms

4-(2, 4-dichloro-5-methoxyphenylamino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphoryl

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Tyrosine-protein kinase Lyn inhibitor

Product Properties

• ALogP: 5.4

Names and Identifiers

• Isomeric SMILES: CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC
• WGK Germany: 3
• Molecular Weight: 530.45
• Reaxy-Rn: 9100307
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=9100307&ln=

Associated Targets(Human)

CTH Tchem Cystathionine gamma-lyase (0 Activities)

Discover Target: CTH

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EPHA2 Tclin Ephrin type-A receptor 2 (1 Activities)

Discover Target: EPHA2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EPHA4 Tchem Ephrin type-A receptor 4 (1 Activities)

Discover Target: EPHA4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EPHA8 Tchem Ephrin type-A receptor 8 (1 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EPHB4 Tchem Ephrin type-B receptor 4 (2 Activities)

Discover Target: EPHB4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ERBB4 Tclin Receptor tyrosine-protein kinase erbB-4 (1 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EPHA5 Tchem Ephrin type-A receptor 5 (1 Activities)

Discover Target: EPHA5

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ERBB3 Tclin Receptor tyrosine-protein kinase erbB-3 (1 Activities)

Discover Target: ERBB3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EGFR Tclin Epidermal growth factor receptor (4 Activities)

Discover Target: EGFR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EPHA3 Tchem Ephrin type-A receptor 3 (1 Activities)

Discover Target: EPHA3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

SRC Tclin Proto-oncogene tyrosine-protein kinase Src (28 Activities)

Discover Target: SRC

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

STK10 Tchem Serine/threonine-protein kinase 10 (2 Activities)

Discover Target: STK10

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

STK24 Tchem Serine/threonine-protein kinase 24 (3 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

STK35 Tchem Serine/threonine-protein kinase 35 (1 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

STK4 Tchem Serine/threonine-protein kinase 4 (1 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TXK Tchem Tyrosine-protein kinase TXK (1 Activities)

Discover Target: TXK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

YES1 Tclin Tyrosine-protein kinase Yes (2 Activities)

Discover Target: YES1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FRK Tchem Tyrosine-protein kinase FRK (4 Activities)

Discover Target: FRK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FYN Tclin Tyrosine-protein kinase Fyn (3 Activities)

Discover Target: FYN

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

GAK Tchem Cyclin-G-associated kinase (3 Activities)

Discover Target: GAK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FGR Tchem Tyrosine-protein kinase Fgr (2 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CAMK1D Tchem Calcium/calmodulin-dependent protein kinase type 1D (1 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

SIK1 Tchem Serine/threonine-protein kinase SIK1 (1 Activities)

Discover Target: SIK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

SIK2 Tchem Serine/threonine-protein kinase SIK2 (2 Activities)

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Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TNIK Tchem TRAF2 and NCK-interacting protein kinase (1 Activities)

Discover Target: TNIK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

SIK3 Tchem Serine/threonine-protein kinase SIK3 (1 Activities)

Discover Target: SIK3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

SLK Tchem STE20-like serine/threonine-protein kinase (1 Activities)

Discover Target: SLK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PKMYT1 Tchem Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (2 Activities)

Discover Target: PKMYT1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MINK1 Tchem Misshapen-like kinase 1 (2 Activities)

Discover Target: MINK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP2K2 Tclin Dual specificity mitogen-activated protein kinase kinase 2 (1 Activities)

Discover Target: MAP2K2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP4K2 Tchem Mitogen-activated protein kinase kinase kinase kinase 2 (2 Activities)

Discover Target: MAP4K2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

LCK Tclin Tyrosine-protein kinase Lck (2 Activities)

Discover Target: LCK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP4K3 Tchem Mitogen-activated protein kinase kinase kinase kinase 3 (2 Activities)

Discover Target: MAP4K3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP4K4 Tchem Mitogen-activated protein kinase kinase kinase kinase 4 (1 Activities)

Discover Target: MAP4K4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP4K5 Tchem Mitogen-activated protein kinase kinase kinase kinase 5 (4 Activities)

Discover Target: MAP4K5

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

LYN Tclin Tyrosine-protein kinase Lyn (4 Activities)

Discover Target: LYN

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

BTK Tclin Tyrosine-protein kinase BTK (3 Activities)

Discover Target: BTK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

BMX Tchem Cytoplasmic tyrosine-protein kinase BMX (2 Activities)

Discover Target: BMX

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

BCR Tclin Breakpoint cluster region protein (1 Activities)

Discover Target: BCR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

BLK Tchem Tyrosine-protein kinase Blk (1 Activities)

Discover Target: BLK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TNK2 Tclin Activated CDC42 kinase 1 (4 Activities)

Discover Target: TNK2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ABL2 Tchem Tyrosine-protein kinase ABL2 (3 Activities)

Discover Target: ABL2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ABL1 Tclin Tyrosine-protein kinase ABL1 (23 Activities)

Discover Target: ABL1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

HCK Tclin Tyrosine-protein kinase HCK (3 Activities)

Discover Target: HCK

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

NTRK2 Tclin BDNF/NT-3 growth factors receptor (1 Activities)

Discover Target: NTRK2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

NTRK1 Tclin High affinity nerve growth factor receptor (1 Activities)

Discover Target: NTRK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CAMK2G Tchem Calcium/calmodulin-dependent protein kinase type II subunit gamma (1 Activities)

Discover Target: CAMK2G

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP2K1 Tclin Dual specificity mitogen-activated protein kinase kinase 1 (2 Activities)

Discover Target: MAP2K1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MAP2K5 Tchem Dual specificity mitogen-activated protein kinase kinase 5 (1 Activities)

Discover Target: MAP2K5

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 47 mg/mL (199.05 mM); Water: 47 mg/mL (199.05 mM); Ethanol: 10 mg/mL (42.35 mM)