7GI

Repotrectinib

Created:	2021-10-01
Last modified:	2021-10-13

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2 entries where 7GI is found as a standalone ligand

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Chemical Details
Formal Charge	0
Atom Count	44
Chiral Atom Count	2
Bond Count	47
Aromatic Bond Count	16

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Chemical Component Summary
Name	Repotrectinib
Formula	C₁₈ H₁₈ F N₅ O₂
Molecular Weight	355.366
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	CACTVS	3.385	C[CH]1CNC(=O)c2cnn3ccc(N[CH](C)c4cc(F)ccc4O1)nc23
SMILES	OpenEye OEToolkits	2.0.7	CC1CNC(=O)c2cnn3c2nc(cc3)NC(c4cc(ccc4O1)F)C
Canonical SMILES	CACTVS	3.385	C[C@H]1CNC(=O)c2cnn3ccc(N[C@H](C)c4cc(F)ccc4O1)nc23
Canonical SMILES	OpenEye OEToolkits	2.0.7	C[C@H]1CNC(=O)c2cnn3c2nc(cc3)N[C@@H](c4cc(ccc4O1)F)C
InChI	InChI	1.03	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
InChIKey	InChI	1.03	FIKPXCOQUIZNHB-WDEREUQCSA-N

Drug Info: DrugBank

DrugBank ID	DB16826 ?
Name	Repotrectinib
Groups	approved investigational
Description	Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) specifically designed to address resistance in the treatment of non-small cell lung cancer (NSCLC), specifically due to mutations in the ROS1 gene.[A262056] ROS1 mutations are one of the defined oncogenic drives of NSCLC, and the solvent-front mutation ROS1 G2032R is responsible for 50 to 60% of [crizotinib]-resistant cases.[A262056] Repotrectinib possesses a compact macrocyclic structure that both limits adverse interactions with resistance mutation hotspots and targets mutations in the solvent-front region.[A262061] Although resistance to multiple TKI has been reported, including [crizotinib], [lorlatinib], [taletrectinib], and [entrectinib], there has been no reported case of repotrectinib resistance.[A262066] On November 15th, 2023, the FDA approved repotrectinib under the brand name Augtyro for the treatment of locally advanced or metastatic ROS1-Positive NSCLC. This approval is based on favorable results from the TRIDENT-1 study, where the objective response rate was 79% in TKI-naive patients and 38% in TKI-pretreated patients respectively.[L48741]
Synonyms	Repotrectinib (7S,13R)-11-Fluoro-7,13-Dimethyl-6,7,13,14-Tetrahydro-1,15-Ethenopyrazolo[4,3-F][1,4,8,10]Benzoxatriazacyclotridecin-4(5H)-One (3R,6S,)-45-FLUORO-3,6-DIMETHYL-5-OXA-2,8-DIAZA-1(5,3)-PYRAZOLO(1,5-A)PYRIMIDINA-4(1,2)-BENZENANONAPHAN-9-ONE 1,15-ETHENO-1H-PYRAZOLO(4,3-F)(1,4,8,10)BENZOXATRIAZACYCLOTRIDECIN-4(5H)-ONE, 11-FLUORO-6,7,13,14-TETRAHYDRO-7,13-DIMETHYL-, (7S,13R)-
Brand Names	Augtyro
Indication	Repotrectinib is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).[L48711] It is also indicated in patients ≥12 years of age and older with neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive solid tumors which are locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have experienced disease progression following treatment or have no satisfactory alternative.[L51028]
Categories	BCRP/ABCG2 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 CYP2B6 Inducers (strength unknown) Cytochrome P-450 CYP2C19 Inducers Cytochrome P-450 CYP2C19 Inducers (strength unknown) Cytochrome P-450 CYP2C8 Inducers Cytochrome P-450 CYP2C8 Inducers (strength unknown) Cytochrome P-450 CYP2C9 Inducers Cytochrome P-450 CYP2C9 Inducers (strength unknown) Cytochrome P-450 CYP3A Inducers Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Inducers Cytochrome P-450 CYP3A4 Inducers (strength unknown) Cytochrome P-450 CYP3A4 Inhibitors Cytochrome P-450 CYP3A4 Inhibitors (strength unknown) Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A5 Inhibitors Cytochrome P-450 CYP3A5 Inhibitors (strength unknown) Cytochrome P-450 Enzyme Inducers Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Substrates Kinase Inhibitor MATE 2 Inhibitors MATE inhibitors OATP1B1/SLCO1B1 Inhibitors P-glycoprotein inhibitors P-glycoprotein substrates ROS1 tyrosine kinase inhibitors Tyrosine Kinase Inhibitors UGT1A1 Inhibitors
CAS number	1802220-02-5

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Proto-oncogene tyrosine-protein kinase ROS	MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTP...	unknown	inhibitor
High affinity nerve growth factor receptor	MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRC...	unknown	inhibitor
BDNF/NT-3 growth factors receptor	MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSP...	unknown	inhibitor
NT-3 growth factor receptor	MDVSLCPAKCSFWRIFLLGSVWLDYVGSVLACPANCVCSKTEINCRRPDD...	unknown	inhibitor
Cytochrome P450 2B6	MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRG...	unknown	inducer
Cytochrome P450 2C8	MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDI...	unknown	inducer
Cytochrome P450 2C9	MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...	unknown	inducer
Cytochrome P450 2C19	MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...	unknown	inducer
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate,inhibitor,inducer
Cytochrome P450 3A5	MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNV...	unknown	inhibitor
UDP-glucuronosyltransferase 1A1	MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQL...	unknown	inhibitor
Broad substrate specificity ATP-binding cassette transporter ABCG2	MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKS...	unknown	inhibitor
Multidrug and toxin extrusion protein 2	MDSLQDTVALDHGGCCPALSRLVPRGFGTEMWTLFALSGPLFLFQVLTFM...	unknown	inhibitor
ATP-dependent translocase ABCB1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	substrate,inhibitor
Solute carrier organic anion transporter family member 1B1	MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKS...	unknown	inhibitor
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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