Repotrectinib (TPX-0005) - Moligand™, 10mM in DMSO , Inhibitor of ALK receptor tyrosine kinase;Inhibitor of c-ros oncogene 1; receptor tyrosine kinase;Inhibitor of Janus kinase 2;Inhibitor of neurotrophic receptor tyrosine kinase 1;Inhibitor of neurotroph, Inhibitor of ALK receptor tyrosine kinase;Inhibitor of c-ros oncogene 1; receptor tyrosine kinase;Inhibitor of Janus kinase 2;Inhibitor of neurotrophic receptor tyrosine kinase 1;Inhibitor of neurotrophic receptor tyrosine kinase 2;Inhibitor of neurotroph

CAS: 1802220-02-5 Cat. No.: R422207 Formula: C₁₈H₁₈FN₅O₂ Peso molecolare: 355.37 Numero EC: 875-681-8 PubChem CID: 135565923

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

SCHEMBL16946804 | NSC800522 | NSC-800522 | (2R)-2-[[6-(benzylamino)-9-propan-2-yl-purin-2-yl]amino]butan-1-ol | (7S,13R)-11-fluoro-6,7,13,14-tetrahydro-7,13-dimethyl-1,15-etheno-1H-pyrazolo[4,3-f][1,4,8,10]benzoxatriazacyclotridecin-4(5H)-one | E102 | BDB

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

Information

Repotrectinib (TPX-0005) Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM).

Targets

ROS1 ; Trk receptor ; WT ALK (Cell-free assay); ALK(L1196M) (Cell-free assay); ALK(G1202R) (Cell-free assay) 27980,; 1.01 nM; 1.08 nM; 1.26 nM

In vitro

TPX-0005 is an orally available and potent ATP-competitive inhibitor against ALK, ROS1, TRKA, TRKB and TRKC recombinant kinases and their corresponding clinical resistant mutants. TPX-0005 demonstrates potent anti-proliferative activity in the range of sub-nanomolar to low nanomolar in a number of human cancer cell lines and engineered stable cell lines expressing the targeted oncogenes or their solvent front mutants, accompanied by inhibition of target phosphorylation and concomitant inactivation of downstream effectors such as ERK, AKT and STAT3. TPX-0005 inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib. TPX-0005 is able to not only inhibit the wild-type and a broad spectrum of mutant ALKs, but also overcome primary resistance and suppress metastatic features by inhibiting SRC.

In vivo

In patient derived xenograft tumor models, TPX-0005 treatment results in significant regression of tumors harboring the oncogenic ALK, ROS1 and TRKC fusions. Moreover, in a series of mouse xenograft tumor models, TPX-0005 exhibits marked anti-tumor activity not only in tumors harboring the wildtype oncogenic targets but also in tumors harboring the oncogenes with the solvent front mutations via inhibition of the target phosphorylation.

Specifications

Sinonimi

SCHEMBL16946804 | NSC800522 | NSC-800522 | (2R)-2-[[6-(benzylamino)-9-propan-2-yl-purin-2-yl]amino]butan-1-ol | (7S,13R)-11-fluoro-6,7,13,14-tetrahydro-7,13-dimethyl-1,15-etheno-1H-pyrazolo[4,3-f][1,4,8,10]benzoxatriazacyclotridecin-4(5H)-one | E102 | BDB

Specifiche e purezza

Moligand™, 10mM in DMSO

Meccanismi biochimici e fisiologici

Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM).

Condizioni di conservazione di stoccaggio

Store at -80°C

Spedito in

Dry ice packs + Cold packs

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Grado

Moligand™

Tipo di azione

INHIBITOR

Meccanismo d'azione

Inhibitor of ALK receptor tyrosine kinase;Inhibitor of c-ros oncogene 1; receptor tyrosine kinase;Inhibitor of Janus kinase 2;Inhibitor of neurotrophic receptor tyrosine kinase 1;Inhibitor of neurotrophic receptor tyrosine kinase 2;Inhibitor of neurotroph

Proprietà del prodotto

ALogP

2.005

Conteggio HBD

2

Nomi e identificatori

Pubchem Sid

528766945

Sorrisi canonici

CC1CNC(=O)C2=C3N=C(C=CN3N=C2)NC(C4=C(O1)C=CC(=C4)F)C

IUPAC Name

(3R,11S)-6-fluoro-3,11-dimethyl-10-oxa-2,13,17,18,21-pentazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaen-14-one

InChIKey

FIKPXCOQUIZNHB-WDEREUQCSA-N

INCHI

1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1

Isomeri SMILES

C[C@H]1CNC(=O)C2=C3N=C(C=CN3N=C2)N[C@@H](C4=C(O1)C=CC(=C4)F)C

PubChem CID

135565923

Peso molecolare

355.37

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Phenylpropanoids and polyketides
    • Classe Macrolactams

• Kingdom: Organic compounds
• Superclass: Phenylpropanoids and polyketides
• Classe: Macrolactams
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Macrolactams
• Alternative Parents: Pyrazolo[1,5-a]pyrimidines Secondary alkylarylamines Alkyl aryl ethers Pyrimidines and pyrimidine derivatives Imidolactams Benzenoids Aryl fluorides Vinylogous amides Pyrazoles Heteroaromatic compounds Secondary carboxylic acid amides Lactams Amino acids and derivatives Oxacyclic compounds Azacyclic compounds Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Macrolactam - Pyrazolo[1,5-a]pyrimidine - Pyrazolopyrimidine - Secondary aliphatic/aromatic amine - Alkyl aryl ether - Imidolactam - Benzenoid - Pyrimidine - Aryl halide - Aryl fluoride - Heteroaromatic compound - Vinylogous amide - Pyrazole - Azole - Secondary carboxylic acid amide - Lactam - Carboxamide group - Amino acid or derivatives - Oxacycle - Azacycle - Organoheterocyclic compound - Secondary amine - Ether - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Aromatic heteropolycyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
• 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

Obiettivi associati (umani)

SRC Tclin Proto-oncogene tyrosine-protein kinase Src (1 Activities)

Discover Target: SRC

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

ROS1 Tclin Proto-oncogene tyrosine-protein kinase ROS (2 Activities)

Discover Target: ROS1

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

ALK Tclin ALK tyrosine kinase receptor (5 Activities)

Discover Target: ALK

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 (2 Activities)

Discover Target: NTRK1

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

NTRK3 Tclin NT-3 growth factor receptor (1 Activities)

Discover Target: NTRK3

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

JAK2 Tclin Tyrosine-protein kinase JAK2 (1 Activities)

Discover Target: JAK2

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

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

JAK2 Tclin Tyrosine-protein kinase JAK2 (12915 Activities)

Discover Target: JAK2

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

HDAC2 Tclin Histone deacetylase 2 (3971 Activities)

Discover Target: HDAC2

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

CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)

Discover Target: CYP2D6

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

NTRK1 Tclin Nerve growth factor receptor Trk-A (7922 Activities)

Discover Target: NTRK1

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

CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)

Discover Target: CYP1A2

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

CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)

Discover Target: CYP2C9

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

CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)

Discover Target: CYP2C19

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

CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)

Discover Target: CYP3A4

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

NCI-H358 (882 Activities)

Explore this target

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

HepG2 (196354 Activities)

Explore this target

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

NCI-H23 (49055 Activities)

Explore this target

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

NTRK2 Tclin Neurotrophic tyrosine kinase receptor type 2 (3279 Activities)

Discover Target: NTRK2

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

ALK Tclin ALK tyrosine kinase receptor (7132 Activities)

Discover Target: ALK

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

ROS1 Tclin Proto-oncogene tyrosine-protein kinase ROS (2436 Activities)

Discover Target: ROS1

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

NTRK3 Tclin NT-3 growth factor receptor (2338 Activities)

Discover Target: NTRK3

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

NCI-H1792 (313 Activities)

Explore this target

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

NCI-H2122 (340 Activities)

Explore this target

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

KARPAS-299 (888 Activities)

Explore this target

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

ALK Tclin EML4-ALK (350 Activities)

Discover Target: ALK

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

NCI-H1373 (66 Activities)

Explore this target

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

Obiettivi associati (non umani)

Hdac1 Histone deacetylase 1 (93 Activities)

Discover Target: Hdac1

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

Hdac6 Histone deacetylase 6 (222 Activities)

Discover Target: Hdac6

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

BaF3 (4657 Activities)

Explore this target

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

Meccanismi d'azione

Proprietà chimiche e fisiche

• DMSO (mg/mL) Solubilità massima: 70
• DMSO (mM) Solubilità massima: 196.9777978
• Acqua (mg/mL) Solubilità massima: ＜1
• Peso molecolare: 355.400 g/mol
• XLogP3: 2.100
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 0
• Exact Mass: 355.144 Da
• Monoisotopic Mass: 355.144 Da
• Topological Polar Surface Area: 80.600 Ų
• Heavy Atom Count: 26
• Formal Charge: 0
• Complexity: 524.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 2
• 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