Q4J

Pralsetinib


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Chemical Component Summary

NamePralsetinib
SynonymsBLU-667; trans-N-{(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]ethyl}-1-methoxy-4-{4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}cyclohexane-1-carboxamide
Identifiers~{N}-[(1~{S})-1-[6-(4-fluoranylpyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1~{H}-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide
FormulaC27 H32 F N9 O2
Molecular Weight533.6
TypeNON-POLYMER
Isomeric SMILESCc1cc(n[nH]1)Nc2cc(nc(n2)C3CCC(CC3)(C(=O)N[C@@H](C)c4ccc(nc4)n5cc(cn5)F)OC)C
InChIInChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19-,27-/m0/s1
InChIKeyGBLBJPZSROAGMF-BATDWUPUSA-N

Chemical Details

Formal Charge0
Atom Count71
Chiral Atom Count1
Bond Count75
Aromatic Bond Count22

Drug Info: DrugBank

DrugBank IDDB15822 
NamePralsetinib
Groups
  • approved
  • investigational
DescriptionPralsetinib, similar to the previously approved [selpercatinib], is a kinase inhibitor with enhanced specificity for RET tyrosine kinase receptors (RTKs) over other RTK classes.[A202055, A219751, L15986] Enhanced RET (Rearranged during transfection) oncogene expression is a hallmark of many cancers, including non-small cell lung cancer. Although multikinase inhibitors, including [cabozantinib], [ponatinib], [sorafenib], [sunitinib], and [vandetanib], have shown efficacy in RET-driven cancers, their lack of specificity is generally associated with substantial toxicity.[A202055] Pralsetinib (BLU-667) and [selpercatinib] (LOXO-292) represent the first generation of specific RET RTK inhibitors for the treatment of RET-driven cancers.[A202049, A202055, L15986] Although a phase 1/2 trial of pralsetinib termed ARROW (NCT03037385) is still ongoing, pralsetinib was granted accelerated FDA approval on September 4, 2020, for the treatment of metastatic RET-fusion positive non-small cell lung cancer. It is currently marketed under the brand name GAVRETO™ by Blueprint Medicines.[L15986]
SynonymsPralsetinib
Brand NamesGavreto
IndicationPralsetinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in adult patients who are confirmed to possess a rearranged during transfection (RET) gene fusion, as determined by an FDA approved test.[L15986] It is also indicated in adult and pediatric patients 12 years of age and older for the treatment of advanced or metastatic _RET_ fusion-positive thyroid cancer who require systemic therapy and for whom radioactive iodine is not appropriate.[L47905] The indication for advanced or metastatic _RET_ fusion-positive thyroid cancer was approved under accelerated approval based on the overall response rate and duration of response, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.[L47905]
Categories
  • Antineoplastic Agents
  • Antineoplastic and Immunomodulating Agents
  • BCRP/ABCG2 Inhibitors
  • BCRP/ABCG2 Substrates
  • BSEP/ABCB11 Inhibitors
ATC-CodeL01EX23
CAS number2097132-94-8

Drug Targets

NameTarget SequencePharmacological ActionActions
Proto-oncogene tyrosine-protein kinase receptor RetMAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPL...unknowninhibitor
Epithelial discoidin domain-containing receptor 1MGPEALSSLLLLLLVASGDADMKGHFDPAKCRYALGMQDRTIPDSDISAS...unknowninhibitor
NT-3 growth factor receptorMDVSLCPAKCSFWRIFLLGSVWLDYVGSVLACPANCVCSKTEINCRRPDD...unknowninhibitor
Receptor-type tyrosine-protein kinase FLT3MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKS...unknowninhibitor
Tyrosine-protein kinase JAK1MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRL...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