Theliatinib (HMPL-309) - Moligand™, ≥96% , Inhibitor of epidermal growth factor receptor;Inhibitor of erb-b2 receptor tyrosine kinase 4;Inhibitor of LCK proto-oncogene; Src family tyrosine kinase;Inhibitor of LYN proto-oncogene; Src family tyrosine kinase, Inhibitor of epidermal growth factor receptor;Inhibitor of erb-b2 receptor tyrosine kinase 4;Inhibitor of LCK proto-oncogene; Src family tyrosine kinase;Inhibitor of LYN proto-oncogene; Src family tyrosine kinase;Inhibitor of tyrosine kinase non receptor

CAS: 1353644-70-8 Cat. No.: T414072 Molecular Weight: 442.51 PubChem CID: 54759275

GRADE & PURITY Moligand™, ≥96%

Synonyms

SCHEMBL247509 | AC-35865 | s8584 | AKOS032946520 | XILIERTINIB [WHO-DD] | 6ZZ3B7NZ0B | Pyrrolo(3,4-b)pyrrole-5(1H)-carboxamide, N-(4-((3-ethynylphenyl)amino)-7-methoxy-6-quinazolinyl)hexahydro-1-methyl-, (3aR,6aR)- | (3aR,6aR)-N-[4-(3-ethynylanilino)-7-me

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Targets

WT EGFR (Cell-free assay); EGFR T790M/L858R (Cell-free assay) 3 nM; 22 nM

In vitro

In comparison to erlotinib or gefitnib, theliatinib shows much stronger binding affinity to wild type EGFR and is more difficult to be replaced by ATP. This unique feature may result in better target engagement for theliatinib compared to erlotinib or gefitinib, leading to stronger anti-tumor activity in tumors with wild type EGFR activation due to gene amplification or protein overexpression. Theliatinib inhibits EGFR phosphorylation with an IC50 of 0.007 μM for EGF stimulated EGFR phosphorylation in A431 cells and cell survival in tumor cells with wild-type EGFR (A431, H292, FaDu cells).

Theliatinib demonstrates dose-dependent anti-tumor activity in a panel of PDECX (patient-derived esophageal cancer xenograft) models with a generally good correlation between EGFR H score and tumor growth inhibition. Furthermore, aberrant activation or gene mutations of other targets such as PI3K and FGFR diminishes the anti-tumor activity of the EGFR TKIs, especially, theliatinib.

Cell Research(from reference)

Cell lines：A431 cells 

Concentrations：0.005-10 μM 

Incubation Time：48 h 

Specifications

Synonyms

SCHEMBL247509 | AC-35865 | s8584 | AKOS032946520 | XILIERTINIB [WHO-DD] | 6ZZ3B7NZ0B | Pyrrolo(3, 4-b)pyrrole-5(1H)-carboxamide, N-(4-((3-ethynylphenyl)amino)-7-methoxy-6-quinazolinyl)hexahydro-1-methyl-, (3aR, 6aR)- | (3aR, 6aR)-N-[4-(3-ethynylanilino)-7-me

Specifications & Purity

Moligand™, ≥96%

Biochemical and Physiological Mechanisms

Theliatinib (HMPL-309) is a highly potent EGFR inhibitor with Ki value of 0.05 nM against the wild type EGFR and IC50 values of 3 nM and 22 nM against EGFR and EGFR T790M/L858R mutant. It demonstrats 50 fold greater selectivity for EGFR compared to 72 oth

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 epidermal growth factor receptor;Inhibitor of erb-b2 receptor tyrosine kinase 4;Inhibitor of LCK proto-oncogene; Src family tyrosine kinase;Inhibitor of LYN proto-oncogene; Src family tyrosine kinase;Inhibitor of tyrosine kinase non receptor

Purity

≥96%

Names and Identifiers

• Pubchem Sid: 528771192
• Canonical Smiles: CN1CCC2C1CN(C2)C(=O)NC3=C(C=C4C(=C3)C(=NC=N4)NC5=CC=CC(=C5)C#C)OC
• IUPAC Name: (3aR,6aR)-N-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]-1-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carboxamide
• InChIKey: FSXCKIBROURMFT-VGSWGCGISA-N
• INCHI: 1S/C25H26N6O2/c1-4-16-6-5-7-18(10-16)28-24-19-11-21(23(33-3)12-20(19)26-15-27-24)29-25(32)31-13-17-8-9-30(2)22(17)14-31/h1,5-7,10-12,15,17,22H,8-9,13-14H2,2-3H3,(H,29,32)(H,26,27,28)/t17-,22+/m1/s1
• Isomeric SMILES: CN1CC[C@H]2[C@@H]1CN(C2)C(=O)NC3=C(C=C4C(=C3)C(=NC=N4)NC5=CC=CC(=C5)C#C)OC
• PubChem CID: 54759275
• Molecular Weight: 442.51

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Diazanaphthalenes
      • Subclass Benzodiazines
        • Level5 Quinazolines
          • Level6 Quinazolinamines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Diazanaphthalenes
• Subclass: Benzodiazines
• Intermediate Tree Nodes: Quinazolines
• Direct Parent: Quinazolinamines
• Alternative Parents: Pyrrolidinecarboxamides Anisoles Alkyl aryl ethers Pyrimidines and pyrimidine derivatives N-alkylpyrrolidines Imidolactams Benzene and substituted derivatives Heteroaromatic compounds Trialkylamines Organic carbonic acids and derivatives Secondary amines Propargyl-type 1,3-dipolar organic compounds Haloacetylenes and derivatives Carboximidamides Azacyclic compounds Amidines Acetylides Organopnictogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Quinazolinamine - Pyrrolidine-1-carboxamide - Pyrrolidine carboxylic acid or derivatives - Anisole - Alkyl aryl ether - Imidolactam - Benzenoid - N-alkylpyrrolidine - Pyrimidine - Monocyclic benzene moiety - Heteroaromatic compound - Pyrrolidine - Tertiary aliphatic amine - Tertiary amine - Carbonic acid derivative - Haloacetylene or derivatives - Acetylide - Azacycle - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Carboximidamide - Secondary amine - Ether - Amidine - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine 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)

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

Discover Target: ERBB4

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

EGFR Tclin Epidermal growth factor receptor (1 Activities)

Discover Target: EGFR

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

YES1 Tclin Tyrosine-protein kinase Yes (1 Activities)

Discover Target: YES1

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

TNK1 Tchem Non-receptor tyrosine-protein kinase TNK1 (1 Activities)

Discover Target: TNK1

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

LCK Tclin Tyrosine-protein kinase Lck (1 Activities)

Discover Target: LCK

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

LYN Tclin Tyrosine-protein kinase Lyn (1 Activities)

Discover Target: LYN

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 (106.21 mM)
• Molecular Weight: 442.500 g/mol
• XLogP3: 3.100
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 442.212 Da
• Monoisotopic Mass: 442.212 Da
• Topological Polar Surface Area: 82.600 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 754.000
• 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