TAK-632 - Moligand™, ≥98% , Inhibitor of aurora kinase B;Inhibitor of B-Raf proto-oncogene; serine/threonine kinase;Inhibitor of fibroblast growth factor receptor 3;Inhibitor of platelet derived growth factor receptor beta;Inhibitor of Raf-1 proto-oncogen, Inhibitor of aurora kinase B;Inhibitor of B-Raf proto-oncogene; serine/threonine kinase;Inhibitor of fibroblast growth factor receptor 3;Inhibitor of platelet derived growth factor receptor beta;Inhibitor of Raf-1 proto-oncogene; serine/threonine kinase;I

CAS: 1228591-30-7 Cat. No.: T413733 Molecular Weight: 554.52 PubChem CID: 46209401

GRADE & PURITY Moligand™, ≥98%

Synonyms

N-[7-cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-yl]cyclopropanecarboxamide | N-(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

TAK-632 is a potent pan-Rafinhibitor withIC50of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf in cell-free assays, respectively, showing less or no inhibition against other tested kinases.

Targets

C-Raf (Cell-free assay); B-Raf (Cell-free assay); Aurora B (Cell-free assay); PDGFRβ (Cell-free assay); FGFR3 (Cell-free assay) 15112,1.4 nM; 8.3 nM; 66 nM ;120 nM; 280 nM

In vitro

TAK-632 inhibits phosphorylation of MEK and ERK in melanoma A375 cells (BRAFV600E) with IC50 of 12 nM and 16 nM, respectively. In human melanoma HMVII cells (NRASQ61K/BRAFG469V), TAK-632 also shows strong inhibition of pMEK and pERK with IC50 of 49 nM and 50 nM, respectively. Moreover, TAK-632 also exhibits antiproliferative activity in both A375 and HMVII cells with GI50 of 66 nM and 200 nM, respectively. TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer because of its slow dissociation from RAF. The combination of TAK-632 and TAK-733 exhibits synergistic antiproliferative effects in BRAF- and NRAS-mutated melanoma cells.

In vivo

TAK-632 shows superior oral bioavailability in both rats and dogs. TAK-632 (3.9–24.1 mg/kg, p.o.) exhibits dose-dependent antitumor efficacy without severe body weight reduction in a melanoma A375 (BRAFV600E) xenograft model and a human melanoma HMVII (NRASQ61K/BRAFG469V) xenograft in rats. In NRAS-mutant melanoma SK-MEL-2 xenograft model, TAK-632 (60 or 120 mg/kg, p.o.) also exhibits potent antitumor efficacy without severe toxicity.

Cell Research(from reference)

Cell lines：A375 and HMVII cells 

Concentrations：~2 μM 

Incubation Time：72 hours 

Specifications

Synonyms

N-[7-cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1, 3-benzothiazol-2-yl]cyclopropanecarboxamide | N-(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide

Specifications & Purity

Moligand™, ≥98%

Biochemical and Physiological Mechanisms

TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf in cell-free assays, respectively, showing less or no inhibition against other tested kinases.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

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

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of aurora kinase B;Inhibitor of B-Raf proto-oncogene; serine/threonine kinase;Inhibitor of fibroblast growth factor receptor 3;Inhibitor of platelet derived growth factor receptor beta;Inhibitor of Raf-1 proto-oncogene; serine/threonine kinase;I

Purity

≥98%

Product Properties

• ALogP: 5.74
• HBD Count: 2
• Rotatable Bond: 8

Names and Identifiers

• Pubchem Sid: 504770683
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504770683
• Canonical Smiles: C1CC1C(=O)NC2=NC3=C(S2)C(=C(C=C3)OC4=CC(=C(C=C4)F)NC(=O)CC5=CC(=CC=C5)C(F)(F)F)C#N
• IUPAC Name: N-[7-cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-yl]cyclopropanecarboxamide
• InChIKey: OJFKUJDRGJSAQB-UHFFFAOYSA-N
• INCHI: 1S/C27H18F4N4O3S/c28-19-7-6-17(12-21(19)33-23(36)11-14-2-1-3-16(10-14)27(29,30)31)38-22-9-8-20-24(18(22)13-32)39-26(34-20)35-25(37)15-4-5-15/h1-3,6-10,12,15H,4-5,11H2,(H,33,36)(H,34,35,37)
• Isomeric SMILES: C1CC1C(=O)NC2=NC3=C(S2)C(=C(C=C3)OC4=CC(=C(C=C4)F)NC(=O)CC5=CC(=CC=C5)C(F)(F)F)C#N
• PubChem CID: 46209401
• MeSH Entry Terms: N-(7-Cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo(d)thiazol-2-yl)cyclopropanecarboxamide;TAK-632
• Molecular Weight: 554.52

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Class Organooxygen compounds
      • Subclass Ethers

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Class: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diarylethers
• Alternative Parents: Trifluoromethylbenzenes Phenylacetamides Anilides Benzothiazoles N-arylamides Phenol ethers Phenoxy compounds Fluorobenzenes Cyclopropanecarboxylic acids and derivatives Aryl fluorides Heteroaromatic compounds Thiazoles Secondary carboxylic acid amides Nitriles Azacyclic compounds Organofluorides Organic oxides Alkyl fluorides Hydrocarbon derivatives Carbonyl compounds Organopnictogen compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Diaryl ether - Trifluoromethylbenzene - Phenylacetamide - 1,3-benzothiazole - Anilide - Phenoxy compound - N-arylamide - Phenol ether - Halobenzene - Fluorobenzene - Aryl fluoride - Aryl halide - Monocyclic benzene moiety - Cyclopropanecarboxylic acid or derivatives - Benzenoid - Thiazole - Heteroaromatic compound - Azole - Carboxamide group - Secondary carboxylic acid amide - Carbonitrile - Organoheterocyclic compound - Carboxylic acid derivative - Azacycle - Nitrile - Organofluoride - Organonitrogen compound - Alkyl halide - Alkyl fluoride - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organic nitrogen compound - Organohalogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

RAF1 Tclin RAF proto-oncogene serine/threonine-protein kinase (4 Activities)

Discover Target: RAF1

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

FGFR3 Tclin Fibroblast growth factor receptor 3 (0 Activities)

Discover Target: FGFR3

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

RIPK3 Tchem Receptor-interacting serine/threonine-protein kinase 3 (0 Activities)

Discover Target: RIPK3

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

PDGFRB Tclin Platelet-derived growth factor receptor beta (0 Activities)

Discover Target: PDGFRB

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

PDGFA Tchem Platelet-derived growth factor subunit A (1 Activities)

Discover Target: PDGFA

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

RIPK1 Tchem Receptor-interacting serine/threonine-protein kinase 1 (0 Activities)

Discover Target: RIPK1

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

BRAF Tclin Serine/threonine-protein kinase B-raf (12 Activities)

Discover Target: BRAF

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

AURKB Tchem Aurora kinase B (0 Activities)

Discover Target: AURKB

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

EGFR Tclin Epidermal growth factor receptor erbB1 (33727 Activities)

Discover Target: EGFR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

INSR Tclin Insulin receptor (5558 Activities)

Discover Target: INSR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

ERBB2 Tclin Receptor protein-tyrosine kinase erbB-2 (7851 Activities)

Discover Target: ERBB2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PDGFRB Tclin Platelet-derived growth factor receptor beta (5195 Activities)

Discover Target: PDGFRB

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

KIT Tclin Stem cell growth factor receptor (10667 Activities)

Discover Target: KIT

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MAPK14 Tchem MAP kinase p38 alpha (12866 Activities)

Discover Target: MAPK14

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

GSK3B Tclin Glycogen synthase kinase-3 beta (11785 Activities)

Discover Target: GSK3B

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CSNK1D Tchem Casein kinase I delta (4546 Activities)

Discover Target: CSNK1D

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SRC Tclin Tyrosine-protein kinase SRC (10310 Activities)

Discover Target: SRC

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

IKBKB Tchem Inhibitor of nuclear factor kappa B kinase beta subunit (5554 Activities)

Discover Target: IKBKB

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

AURKB Tchem Serine/threonine-protein kinase Aurora-B (6805 Activities)

Discover Target: AURKB

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

RAF1 Tclin Serine/threonine-protein kinase RAF (4169 Activities)

Discover Target: RAF1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)

Discover Target: KDR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MAP2K1 Tclin Dual specificity mitogen-activated protein kinase kinase 1 (4127 Activities)

Discover Target: MAP2K1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MET Tclin Hepatocyte growth factor receptor (10718 Activities)

Discover Target: MET

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MAPK3 Tchem MAP kinase ERK1 (4725 Activities)

Discover Target: MAPK3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MAPK8 Tchem c-Jun N-terminal kinase 1 (5038 Activities)

Discover Target: MAPK8

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MAP3K1 Tchem Mitogen-activated protein kinase kinase kinase 1 (590 Activities)

Discover Target: MAP3K1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PRKCQ Tchem Protein kinase C theta (3319 Activities)

Discover Target: PRKCQ

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

TEK Tclin Tyrosine-protein kinase TIE-2 (3348 Activities)

Discover Target: TEK

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CHEK1 Tchem Serine/threonine-protein kinase Chk1 (6846 Activities)

Discover Target: CHEK1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

A-375 (9258 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HT-29 (80576 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SK-MEL-2 (46422 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

A549 (127892 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HMCB cell line (13 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HMV-2 cell line (109 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HepG2 (196354 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HeLa (62764 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Malme-3M (44254 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRAF Tclin Serine/threonine-protein kinase B-raf (11587 Activities)

Discover Target: BRAF

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

RIPK1 Tchem Receptor-interacting serine/threonine-protein kinase 1 (1548 Activities)

Discover Target: RIPK1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CHL-1 (186 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

RIPK3 Tchem Receptor-interacting serine/threonine-protein kinase 3 (468 Activities)

Discover Target: RIPK3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CDK1 Tchem Cyclin-dependent kinase 1/cyclin B1 (1887 Activities)

Discover Target: CDK1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PIR Tchem Pirin (51 Activities)

Discover Target: PIR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HT-144 (176 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CDK2 Tchem CDK2/Cyclin A2 (2260 Activities)

Discover Target: CDK2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PDGFA Tchem Platelet-derived growth factor subunit A (2 Activities)

Discover Target: PDGFA

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

RAF1 Tclin B-raf/RAF proto-oncogene serine/threonine-protein kinase (20 Activities)

Discover Target: RAF1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

Hdac6 Histone deacetylase 6 (222 Activities)

Discover Target: Hdac6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Fgfr3 Fibroblast growth factor receptor 3 (21 Activities)

Discover Target: Fgfr3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Canis familiaris (36305 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mus musculus (284745 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Rattus norvegicus (775804 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Hsf1 Heat shock factor protein 1 (5445 Activities)

Discover Target: Hsf1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

IEC-6 (77 Activities)

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Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 100 mg/mL (180.33 mM); Ethanol: 2 mg/mL (3.6 mM); Water: Insoluble
• DMSO(mg / mL) Max Solubility: 100
• DMSO(mM) Max Solubility: 180.3361466
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 554.500 g/mol
• XLogP3: 5.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 7
• Exact Mass: 554.104 Da
• Monoisotopic Mass: 554.104 Da
• Topological Polar Surface Area: 132.000 Ų
• Heavy Atom Count: 39
• Formal Charge: 0
• Complexity: 957.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1