Details of the Drug

General Information of Drug (ID: DMZR15V)

Drug Name
Selpercatinib
Synonyms MFOVQWYFURMVKU-IWAAJCSBSA-N; 2222755-14-6; LOXO292; ARRY-192; LOXO 292; EX-A2636
Indication
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [1]
Thyroid cancer 2D10 Approved [1]
Colon cancer 2B90.Z Phase 1/2 [2]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 542.6
Topological Polar Surface Area (xlogp) 1.4
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2.5 h [3]
Bioavailability
The bioavailability of drug is 89.9% [3]
Clearance
The clearance of drug is 6 L/h [4]
Elimination
Selpercatinib administered as a single 160 mg dose in healthy individuals was primarily recovered in feces (69%, 14% unchanged) and urine (24%, 12% unchanged) [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 32 hours [4]
Metabolism
The drug is metabolized via the liver [4]
Vd
The volume of distribution (Vd) of drug is 191 L [4]
Chemical Identifiers
Formula
C29H34N8O3
IUPAC Name
(2S)-2-[[4-[5-[6-[(6-methoxypyridin-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]pyrazin-2-yl]-3-methylpyrazolo[1,5-a]pyridin-6-yl]oxymethyl]morpholine
Canonical SMILES
CC1=C2C(=CC(=CN2N=C1)OC[C@@H]3CNCCO3)C4=CN=C(C=N4)N5CC6CC(C5)N6CC7=CN=C(C=C7)OC
InChI
InChI=1S/C29H34N8O3/c1-19-9-34-37-17-23(40-18-24-11-30-5-6-39-24)8-25(29(19)37)26-12-32-27(13-31-26)35-15-21-7-22(16-35)36(21)14-20-3-4-28(38-2)33-10-20/h3-4,8-10,12-13,17,21-22,24,30H,5-7,11,14-16,18H2,1-2H3/t21?,22?,24-/m0/s1
InChIKey
MFOVQWYFURMVKU-IWAAJCSBSA-N
Cross-matching ID
PubChem CID
134823904
DrugBank ID
DB15685
TTD ID
D01KOA

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-small-cell lung cancer
ICD Disease Classification 2C25.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Proto-oncogene c-Ret (RET) DTT RET 3.48E-02 -0.23 -1.17
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2 ClinicalTrials.gov (NCT03157128) A Study of LOXO-292 in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001). U.S. National Institutes of Health.
3 Garg DC, Wagner JG, Sakmar E, Weidler DJ, Albert KS: Rectal and oral absorption of methylprednisolone acetate. Clin Pharmacol Ther. 1979 Aug;26(2):232-9. doi: 10.1002/cpt1979262232.
4 FDA Approved Drug Products: Retevmo (selpercatinib) capsules
5 Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem. 2010 Feb 15;18(4):1482-96.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
9 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2185).
10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11 Clinical pipeline report, company report or official report of Turning Point Therapeutics.
12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13 National Cancer Institute Drug Dictionary (drug name Zeteletinib).