Drug Information

Drug (ID: DG01604) and It's Reported Resistant Information

• Name: CEP-28122
• Synonyms: CEP-28122; 1022958-60-6; CHEMBL2064666; compound 25b [PMID: 22564207]; (1S,2S,3R,4R)-3-((5-chloro-2-(((S)-1-methoxy-7-morpholino-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)amino)pyrimidin-4-yl)amino)bicyclo[2.2.1]hept-5-ene-2-carboxamide.; CEP28122; CEP 28122; GTPL8139; SCHEMBL2061951; (1S,2S,3R,4R)-3-[(5-chloro-2-{[(7S)-1-methoxy-7-(morpholin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]amino}pyrimidin-4-yl)amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide; EX-A1541; BDBM50389154; ZINC84654307; CS-5176; NCGC00387821-03; HY-18030; Q27076467; (1S,2S,3R,4R)-3-[(5-Chloro-2-{[(7S)-1-methoxy-7-(4-morpholinyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]amino}-4-pyrimidinyl)amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide; (1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide; (1S,2S,3R,4R)-3-[5-Chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Investigative; [1]
• Target: Bacterial 16S ribosomal RNA (Bact 16S rRNA); NOUNIPROTAC; [1]
• Target: Bacterial Ribosomal ATPase RbbA (Bact rbbA); RBBA_ECOLI; [1]
• Formula: 7
• IsoSMILES: COC1=C(C=CC2=C1CC[C@H](CC2)N3CCOCC3)NC4=NC=C(C(=N4)N[C@@H]5[C@@H]6C[C@H]([C@@H]5C(=O)N)C=C6)Cl
• InChI: InChI=1S/C28H35ClN6O3/c1-37-25-20-8-7-19(35-10-12-38-13-11-35)6-4-16(20)5-9-22(25)32-28-31-15-21(29)27(34-28)33-24-18-3-2-17(14-18)23(24)26(30)36/h2-3,5,9,15,17-19,23-24H,4,6-8,10-14H2,1H3,(H2,30,36)(H2,31,32,33,34)/t17-,18+,19+,23+,24-/m1/s1
• InChIKey: LAJAFFLJAJMYLK-CVOKMOJFSA-N
• PubChem CID: 57325421
• TTD Drug ID: D0S6RD

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: ALK tyrosine kinase receptor (ALK) [1]

• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Molecule Alteration: Missense mutation; p.F1174L (c.3520T>C)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.75 Å; PDB: 3AOX
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 1.75 Å; PDB: 4FNW

RMSD: 0.34; TM score: 0.99391; Amino acid change: F1174L

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.F1174L (c.3520T>C) in gene ALK cause the sensitivity of CEP-28122 by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [1]

• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Molecule Alteration: Missense mutation; p.R1275Q (c.3824G>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.R1275Q (c.3824G>A) in gene ALK cause the sensitivity of CEP-28122 by aberration of the drug's therapeutic target

References

• Ref 1: CEP-28122, a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancersMol Cancer Ther. 2012 Mar;11(3):670-9. doi: 10.1158/1535-7163.MCT-11-0776. Epub 2011 Dec 27.