Details of the Drug

General Information of Drug (ID: DMOEARH)

Drug Name
AZD2014
Synonyms
AZD2014; 1009298-59-2; Vistusertib; AZD-2014; AZD 2014; UNII-0BSC3P4H5X; 0BSC3P4H5X; cc-551; 3-[2,4-Bis((3S)-3-methylmorpholin-4-yl)pyrido[5,6-e]pyrimidin-7-yl]-N-methylbenzamide; CHEMBL2336325; 3-[2,4-Bis((3S)-3-methyLmorpholin-4-yl)pyrido-[5,6-e]pyrimidin-7-yl]-N-methylbenzamide; C25H30N6O3; 3-(2,4-bis((S)-3-methylmorpholino)pyrido[2,3-d]pyrimidin-7-yl)-N-methylbenzamide; 3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide; Vistusertib [INN]; Vistusertib [USAN]; Vistusertib (JAN/INN)
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 462.5
Logarithm of the Partition Coefficient (xlogp) 2.8
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C25H30N6O3
IUPAC Name
3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide
Canonical SMILES
C[C@H]1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=CC=C4)C(=O)NC)N5CCOC[C@@H]5C
InChI
InChI=1S/C25H30N6O3/c1-16-14-33-11-9-30(16)23-20-7-8-21(18-5-4-6-19(13-18)24(32)26-3)27-22(20)28-25(29-23)31-10-12-34-15-17(31)2/h4-8,13,16-17H,9-12,14-15H2,1-3H3,(H,26,32)/t16-,17-/m0/s1
InChIKey
JUSFANSTBFGBAF-IRXDYDNUSA-N
Cross-matching ID
PubChem CID
25262792
CAS Number
1009298-59-2
DrugBank ID
DB11925
TTD ID
D0Z2UQ
INTEDE ID
DR1837
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Mammalian target of rapamycin complex 1 (mTORC1) TTX4GLS MTOR_HUMAN-RPTOR_HUMAN-LST8_HUMAN-AKTS1_HUMAN-DPTOR_HUMAN Inhibitor [2]
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [3]
Target of rapamycin complex 2 MAPKAP1 (MTORC2) TTWDKCL SIN1_HUMAN Inhibitor [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [4]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Gene/Protein Processing [5]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Post-Translational Modifications [5]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Gene/Protein Processing [5]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Post-Translational Modifications [5]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Gene/Protein Processing [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Serine/threonine-protein kinase mTOR (mTOR) DTT MTOR 2.16E-05 -0.44 -2.3
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 1.73E-04 1.53E-01 7.44E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 3.51E-02 1.53E+00 1.16E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.84E-01 -1.61E-01 -3.61E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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. (Ligand id: 7699).
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12.
4 First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 inhibitor AZD2014. Clin Cancer Res. 2015 Aug 1;21(15):3412-9.
5 Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.