6GY

5-chloro-N~4~-[2-(dimethylphosphoryl)phenyl]-N~2~-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine

Created: 2016-04-07
Last modified:  2021-03-01

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Chemical Details

Formal Charge0
Atom Count79
Chiral Atom Count0
Bond Count83
Aromatic Bond Count18
2D diagram of 6GY
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Chemical Component Summary

Name5-chloro-N~4~-[2-(dimethylphosphoryl)phenyl]-N~2~-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine
SynonymsBrigatinib
Systematic Name (OpenEye OEToolkits)5-chloranyl-~{N}4-(2-dimethylphosphorylphenyl)-~{N}2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine
FormulaC29 H39 Cl N7 O2 P
Molecular Weight584.092
TypeNON-POLYMER

Chemical Descriptors

TypeProgram Version Descriptor
SMILESACDLabs12.01c1(cnc(nc1Nc2c(P(C)(=O)C)cccc2)Nc3ccc(cc3OC)N4CCC(CC4)N5CCN(CC5)C)Cl
SMILESCACTVS3.385COc1cc(ccc1Nc2ncc(Cl)c(Nc3ccccc3[P](C)(C)=O)n2)N4CCC(CC4)N5CCN(C)CC5
SMILESOpenEye OEToolkits2.0.4CN1CCN(CC1)C2CCN(CC2)c3ccc(c(c3)OC)Nc4ncc(c(n4)Nc5ccccc5P(=O)(C)C)Cl
Canonical SMILESCACTVS3.385 COc1cc(ccc1Nc2ncc(Cl)c(Nc3ccccc3[P](C)(C)=O)n2)N4CCC(CC4)N5CCN(C)CC5
Canonical SMILESOpenEye OEToolkits2.0.4 CN1CCN(CC1)C2CCN(CC2)c3ccc(c(c3)OC)Nc4ncc(c(n4)Nc5ccccc5P(=O)(C)C)Cl
InChIInChI1.03 InChI=1S/C29H39ClN7O2P/c1-35-15-17-37(18-16-35)21-11-13-36(14-12-21)22-9-10-24(26(19-22)39-2)33-29-31-20-23(30)28(34-29)32-25-7-5-6-8-27(25)40(3,4)38/h5-10,19-21H,11-18H2,1-4H3,(H2,31,32,33,34)
InChIKeyInChI1.03 AILRADAXUVEEIR-UHFFFAOYSA-N

Drug Info: DrugBank

DrugBank IDDB12267 
NameBrigatinib
Groups
  • approved
  • investigational
DescriptionBrigatinib, originally named AP26113, is a reversible dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It presents selectivity against the mutant forms of EGFR compared to the wild-type.[A31311] It also exhibits selectivity against 9 different Crizotinib-resistant mutants of the EML4-ALK fusion gene, which is a pivotal player in the transformation of susceptible lung parenchyma.[A31313] Brigatinib was developed by Ariad Pharmaceuticals, a subsidiary of Takeda Pharmaceutical Company Limited, and FDA-approved on April 28, 2017.[L1026]
SynonymsBrigatinib
Brand NamesAlunbrig
IndicationThe anaplastic lymphoma kinase positive, metastatic non-small cell lung cancer (ALK+ NSCLC), represents only 3-5% of the NSCLC cancer cases, but the ALK mutation, overexpression and presence in several oncogenic fusion proteins in solid and hematologic tumors have pointed out the importance as well as its potential as a cancer therapy target.[A31311] The ALK-related cases of NSCLC are associated with the presence of the fusion gene EML4-ALK which fused the ALK protein with the echinoderm microtubule-associated protein like-4 whose original function is the correct formation of microtubules.[A31313] The presence of the aberrant fusion protein results in abnormal signaling that provokes increased cell growth, proliferation and survival.[A31316] Crizotinib is indicated for the treatment of such cases but the presence of ALK kinase domain mutations confer resistance to the treatment. Thus, brigatinib is indicated for the treatment of patients with ALK+ NSCLC with intolerance to Crizotinib.[A31314]
Categories
  • Anaplastic lymphoma kinase (ALK) inhibitors
  • Antineoplastic Agents
  • Antineoplastic and Immunomodulating Agents
  • BCRP/ABCG2 Inhibitors
  • BCRP/ABCG2 Substrates
ATC-CodeL01ED04
CAS number1197953-54-0

Drug Targets

NameTarget SequencePharmacological ActionActions
ALK tyrosine kinase receptorMGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQ...unknowninhibitor
Epidermal growth factor receptorMRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLS...unknowninhibitor
Tyrosine-protein kinase ABL1MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNS...unknowninhibitor
Insulin-like growth factor 1 receptorMKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLE...unknowninhibitor
Receptor-type tyrosine-protein kinase FLT3MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKS...unknowninhibitor
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Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682

Related Resource References

Resource NameReference
Pharos CHEMBL3545311
PubChem 68165256
ChEMBL CHEMBL3545311